A STAR Research October 2017 - December 2017

Issue 9 | October - December 2017
CANCER
CATCHERS
Creating new
diagnostic
tools to detect
diseases earlier
MATTERS OF
THE HEART
Uniting to fight
cardiovascular
disease
BETTER
BATTERIES
Encased sulfur
key to lithium-ion
capacity
DIABETES
RESEARCH
MADE
EASIER
Pancreatic
stem cell
supply secured
Download the A*STAR Research app
Clear. Concise. Convenient.
www.research.a-star.edu.sg/mobile
CONTENTS | F E AT U R E S | RESEARCH HIGHLIGHTS | I M AG E H I G H L I G H T
EDITORIAL
3 Notes from the editors
F E AT U R E S &
I N N O VAT I O N S
4 Attracting the best to fight
heart failure
8 Diagnostic tools in the fast lane
RESEARCH
HIGHLIGHTS
12 Chromosomes find
the perfect match
14 Eyes open to a protective mutation

15 Fast flow to safety
IMAG E HIG H LIG HT

16 A hair-raising image
RESEARCH
4 F E AT U R E S &
I N N O VAT I O N S
HIGHLIGHTS
17 What makes brains grow smooth
and small?
18 A dengue treatment that is one

‘four’ all
19 Producing top-notch 2D materials

20 Like father like child for
weight gain
22 Making HIV drugs work longer

23 Building a barrier
against oxidation
12 20 24 Seeing the big picture
www.research.a-star.edu.sg A*STAR RESEARCH 1

RESEARCH
HIGHLIGHTS
25 A protein to make sperm
26 Polymers are tough on
microbes, soft on skin
27 Unraveling the complexity

28 A sputtering step closer to
cheaper solar cells
30 Heavy legacy of Mum’s

sweet tooth
31 Unlocking magnetic skyrmions

32 A bit of perfection
33 Lupus link to stimulatory proteins
34 Leaving lead behind
35 Invisibility is within sight
36 The role of crystals in the ‘disease
of kings’
38 How stomach tumors hide
28 39 Unleashing sulfur’s potential

40 Mutation discovered for
joint disorder
41 Pancreatic stem cells on tap

42 Fishing for a disease gene
43 Fine-tuning excitation for survival
44 New hope for eczema sufferers
45 Simulating surfactants
30 46 New strategy for fighting invaders
47 Better properties for a
magnesium alloy
48 Better ways with X-rays

50 A guidebook for exotic states
51 How a common cancer hijacks
a wound-healing switch
51 44
52 Getting a functional protein
from A to B
2 A*STAR RESEARCH Issue 9 | October – December 2017

NOTES
FROM THE EDITORS
Editorial board member, Florent Ginhoux, introduces
the latest issue of A*STAR Research
W
elcome to the first edition of four serotypes of dengue (page 18) — both Issue 9 | October - December 2017
A*STAR RESEARCH
A*STAR Research for 2018, of which have important implications on

where we highlight some of the vaccine development. And on the genetics
latest cutting-edge research and side, while mutations are often detrimental
innovations from A*STAR. to health, for example in a joint disorder CANCER
CATCHERS
Our cover story this issue introduces the called arthrogryposis (page 40), they can also
Creating new
diagnostic
tools to detect
diseases earlier
Diagnostics Development (DxD) Hub — a occasionally offer protection against certain MATTERS OF
THE HEART
Uniting to fight
cardiovascular
nationally funded program led by ETPL, diseases, such as glaucoma (page 14).
disease
BETTER
BATTERIES
Encased sulfur
key to lithium-ion
A*STAR’s commercialization arm, which A couple of interesting innovations in

capacity
DIABETES
ISSUE 9 October - December 2017
RESEARCH
MADE
accelerates the journey of diagnostics devices renewable energy materials are also presented — EASIER
Pancreatic
stem cell
supply secured
from lab to market (page 8). And continuing a novel cathode material for lithium-ion batteries
on from our previous issue’s cover story, which that can potentially increase battery capacity COVER IMAGE
discussed the insidious obesity problem in Asia, severalfold (page 39), and a simple and cost- Diagnostic tests are being
fast-tracked by Singapore’s
our second feature story this issue investigates effective technique for manufacturing solar cells DxD Hub. [page 8]
an important but elusive problem — that of out of non-toxic common materials (page 28).
© Colin Anderson/Photographer’s Choice RF/Getty
heart failure, which affects roughly 26 million And another group of researchers have found
people worldwide (page 4). a way to make tunable magnetic skyrmions
We also showcase exciting developments that could lead to next-generation memory and
in the immunity field, including the computing technologies (page 31).
identification of a new key immune cell subtype There are many more fascinating and ex-
in human blood, ‘pre-DC’, as a precursor of citing stories from A*STAR researchers in this
dendritic cells (page 27), and the discovery issue, I hope you will enjoy the rest of our newly
of a potent antibody that can neutralize all redesigned magazine.

ATTRACTING
THE BEST
TO FIGHT
HEART
FAILURE
A new initiative will investigate the causes of
heart failure in unprecedented detail.
A
n A*STAR-led Hospital and Singapore General
study into heart Hospital. Together, this all-star
failure, the largest cast is throwing the weight of
ever conducted Singapore’s scientific expertise
in Singapore, is and resources at heart disease,
revealing new ways to predict one of the country’s biggest
death or admission to hospital killers, responsible for roughly
for people who have suffered 30 per cent of all deaths.
heart failure, as well as opening “ATTRaCT is the first inte-
potential new avenues to reduce grated platform for translational
the risk of heart failure occurring. cardiovascular research that
It’s all part of the Asian leverages Singapore’s competitive
neTwork for Translational advantages to identify and vali-
Research and Cardiovascular date novel targets in heart disease
Trials (ATTRaCT), a S$30 progression,” says Carolyn Lam, a
million government-backed professor at the Duke-NUS Med-
initiative that for the first time ical School and senior consultant
has brought together leading cardiologist at the National Heart
cardiologists and heart disease Centre Singapore, who is leading
researchers from A*STAR, the the program.
National University of Singapore Launched in 2015, ATTRaCT
(NUS), the Duke-NUS Medical builds on previous Singapore-
© Matthias Tunger/ Getty images
School and two national heart led initiatives such as the Asian
institutions (National University Sudden Cardiac Death in Heart
Heart Centre and National Failure (ASIAN-HF) registry, an
Heart Centre Singapore). Also 11-nation study of more than
involved are Singapore’s Khoo 6,000 heart failure patients.
Teck Puat Hospital, Tan Tock However, ATTRaCT goes much
Seng Hospital, Changi General further, using advanced cardiac

“This all-star cast is

throwing the weight
of Singapore’s
scientific expertise
and resources at
heart disease, one of
the country’s biggest
killers, responsible for
roughly 30 per cent
of all deaths.”
The Asian neTwork for

Translational Research
and Cardiovascular
Trials (ATTRaCT) is a
$30 million govern-
ment-backed initiative
has for the first time
has brought together
leading cardiologists
and heart disease
researchers.

imaging, genetic and molecular that leaders of the A*STAR Bioin- differences in the two distinct
studies to look at the root causes formatics Institute were enlisted forms of heart failure, each of
of heart diseases in patients and to help with its management and which is defined by the amount
animal models. analysis. Those clinical findings of blood pumped out of the heart
were then fed into the program’s with each beat.
HE A RT O F T HE M ATTER more basic discovery efforts. For about half of patients with
The linchpin of the program is The goal, says Lam, is to bet- heart failure, blood volume is
a nationwide prospective study ter understand the mechanisms reduced, causing what is known as
involving Singaporeans with heart underlying disease progression heart failure with reduced ejection
failure and healthy controls. Over so researchers can identify fraction, or HFrEF, a problem that
The study three years, each of the trial’s molecular pathways that can be can be treated with drugs that help
is the first 1,200 participants will undergo a targeted to prevent heart failure. maintain fluid balance in the body.
battery of sophisticated diagnostic The ATTRaCT investigators also The other half maintain what
large-scale tests. These include magnetic hope to develop new imaging seems like normal blood volumes,
trial in Asia resonance imaging to view the modalities or blood-based tests but the heart muscle thickens and
that seeks heart’s anatomy and the health of for detecting early signs of becomes stiff, limiting its capacity
its tissues. Blood samples are also pre-symptomatic disease, as well to meet the body’s needs. This
to unravel examined for novel molecular as reveal the genetic factors re- is known as heart failure with
differences in and immunologic indicators sponsible for predisposing people preserved ejection fraction, or
the two dis- of disease. Also, geneticists to heart issues. HFpEF, and it has no effective
are decoding the full genome remedies — in part because so
tinct forms of sequence of each individual. AN UNMET MEDICAL NEED little is known about what drives
heart failure. The clinical part of the study is The study is the first large-scale this muscle thickening and why,
yielding a wealth of data, so much trial in Asia that seeks to unravel for instance, women are more
THE TWO TYPES OF

HEART FAILURE
Heart failure with preserved
Either blood
ejection fraction (HFpEF)
volume
• Heart muscle thickens
and becomes stiff is reduced or
• No effective treatment muscles thicken.
and little understood
© intueri/ Getty images

Heart failure with reduced
ejection fraction (HFrEF)
• Blood volume is reduced
• Can be treated with
drugs that help maintain
fluid balance in the body
CARDIOVASCULAR FAILURE
© Centre Jean Perrin, ISM/Science Photo Library
A scan shows reduced

heart activity in a patient
with heart failure. The
ATTRaCT program is the
first large-scale trial in
the world that seeks
to unravel differences
between heart failure
when blood volume
is reduced and heart
failure when the heart
muscle thickens and
becomes stiff.

HEALING HEARTS FOR predisposed to HFpEF than men. women with HFpEF, potentially
THE FIRST TIME “Fundamentally,” says Roger Foo shedding light on the female
Drugs blocking Singheart
RNA molecules in heart
of the A*STAR Genome Institute predisposition to the disease.
tissue (labelled in red of Singapore, “we still need to Notably, the discovery of a
fluorescent dyes below) understand what the biology of molecule in the blood of patients
may help heal heart failure,
rather than merely slowing
that disease is.” with HFpEF, known to be the
progression. The team led Foo is one of ATTRaCT’s target of a drug that’s already
by Professor Roger Foo note leaders, in charge of all research widely used for other types
that blocking the RNA helps
promote heart repair and
related to genetics and epigenet- of diseases, suggests that the
regeneration in mice. ics. Other leaders include Patrick same drug could conceivably be
Cozzone, executive director of repurposed to help deal with the
the A*STAR Singapore Bioim- unique pathology of HFpEF.
aging Consortium, who runs the Foo and his colleagues also
imaging track of the study, and recently identified an RNA
Mark Richards, a cardiologist who molecule (pictured left, in
directs the NUS Cardiovascular red) involved in regulating the
Research Institute and is heading heart’s response to stress. This
efforts to discover blood biomark- molecule, they reported in the
ers of disease. The ATTRaCT journal Nature Communications,
© SCHMaster/ Getty images
network also collaborates with is active in diseased heart tissue

several of the largest pharmaceuti- from patients, and blocking it
cal companies in the world. helped promote heart repair and
“It’s an impressive research regeneration in mice.1 Currently,
team—multi-national, mul- notes Foo, no known therapies
ti-disciplinary and multi-insti- can do that—all existing heart
tutional,” says John McMurray, a medications merely slow disease
Blocking cardiologist at the University of progression. Now, he says, “the
Reproduced from Ref. 1 and licensed under CC-BY-4.0 (https://creativecommons.org/licenses/by/4.0/) © 2017 K. See et al.
Singheart RNA
molecules (red)
Glasgow’s Institute of Cardio- question is: can we heal the heart
helped promote vascular and Medical Sciences and cause recovery and reverse
heart repair in Scotland, who serves on disease in patients?”
the external scientific review By mid-2019, when
committee for ATTRaCT. “I’ve ATTRaCT has run its course,
reviewed initiatives like this in Lam hopes the platform will
other countries, but this one is transform from an observational
special, helped by charismatic, one for target discovery, to an
strong and focused leadership, interventional one for precision
and sympathetic and supportive trials in heart disease. At that
government oversight.” point, novel and repurposed
drugs discovered in the first phase
INITIA L F IND ING S of the program should be ready
ATTRaCT is only just past for clinical testing in patients. “To
the halfway mark, but has already achieve this,” she says, “continued
spurred a number of seminal strong partnership among the
discoveries. For example, the clinical and research institutions,
study investigators have filed to as well as between academia and
patent a new imaging technique industry, are essential.”
that can track metabolism in the
heart muscle like never before. 1. See, K., Tan, W.L.W., Lim, E.H.,
Tiang, Z., Lee, L.T., et al. Single
They’ve also pinpointed cardiomyocyte nuclear transcrip-
a molecule circulating in the tomes reveal a lincRNA-regulated
de-differentiation and cell cycle
bloodstream of patients that stress-response in vivo. Nature
predicts outcomes specifically in Communications 8, 225 (2017)

DIAGNOSTIC
TOOLS
IN THE FAST
LANE
Diagnostics tests are the key to the early
detection and treatment of diseases — and
Singapore’s Diagnostics Development (DxD) Hub
is accelerating the rate at which devices make it
from the lab to market.
C
ancer could become Singaporean government’s
a chronic condition Innovation Cluster Programme,
rather than a and its work covers a number
terminal sentence of key areas: to make sure that
with the right researchers with intellectual
diagnostic tools, says Sidney Yee, property (IP) connect with the
CEO of the almost 4-year-old right business partners; to test
Diagnostics Development (DxD) their findings to make sure
Hub, a national initiative led by they are clinically reproducible;
A*STAR’s commercialization to design application devices
arm, ETPL. “I strongly believe that meet regulatory standards;
the key to managing oncology is to look for pain points in the
early detection. And, if we can adoption of a diagnostics
make minimally invasive or non- tool; and, to mine data from
invasive tests, it’s convenient, Singaporean research spanning
which means people can test the last two decades for insights
more frequently if they have a that could be turned into useful
high-risk profile.” Sometimes, diagnostic tests. “We don’t do
however, research that could any of the research,” says Yee. With the right kind
make this possible isn’t making it “Instead we develop already of diagnostics tests,
© Dana Neely/Getty Images
to doctors and patients. existing IP that has sufficient check-ups could

be administered
Founded in 2014, the DxD evidence to support diagnostic more often to at-
Hub’s role is to accelerate the use, meet clinical needs, and risk populations and
process of taking diagnostic have a market demand. The cancers caught and
treated earlier.
devices to market. The hub output of that co-development
was seeded as part of the is actually a regulatory dossier

“It is expensive and

invasive for people
with a high-risk
profile to be doing
these scope tests
all the time. Some
countries hugely
subsidize scope tests
for at-risk parts of
the population, yet
we still see gastric
cancers that are
detected late.”

Here a technician does

a simulated scope test
using a mannequin.
Endoscopy tests
done with a scope,
or similar tests for
gastric cancers done
with gastroscopes,
are uncomfortable
and expensive and
may stop at-risk
populations from being
tested more often.
MAKING BETTER Cutting-edge research

DIAGNOSTIC TOOLS is revealing that many
FOR GASTRIC CANCER microRNA levels change
One of the DxD Hub’s first during disease and, as
diagnostic tools to jump they become accessible
the regulatory hurdles is via blood tests, they
a genome liquid biopsy make good diagnostics
test (i.e. a test taken from biomarkers. The genome
a blood sample) for the liquid biopsy test sprang
early detection of gastric from a microRNA that goes to the government From her experience as both
cancer. Gastric cancer, platform that A*STAR and regulatory authorities the DxD Hub’s CEO and an
which kills more than the National University for approval.” executive vice president at the
700,000 people worldwide of Singapore had been The DxD Hub’s framework ETPL, Yee observes that while
each year, is currently developing for some years. means it invests in diagnostics scientific creators of IP possess
only detectable via an That team partnered all the way to the market stage.
uncomfortable inspection with commercial cancer “My job is not finished when
using a long tube called diagnostics company something gets regulatory
a gastroscope. “It is MiRXES, an early DxD approval. I also have to
expensive and invasive for Hub collaborator and a make sure that it reaches its
people with a high-risk spin-off company from intended patients,” Yee says.
profile to be doing these A*STAR’s Bioprocessing This, as well as an accessible
scope tests all the time. Technology Institute, to do and standardized legal
Some countries like Japan some of the most extensive framework for sharing
and Korea, with among clinical trials of these IP, signals to commercial
some of the highest rates types of tests in the world. partners that their initial
of gastric cancer in the GastroClear was recently input will quickly result
world, hugely subsidize approved for the European in something useful to
scope tests for at-risk market of 32 countries, the market. From a national
parts of the population, and the collaboration perspective, she says, that’s
yet we still see gastric hopes to introduce the test an ideal outcome: “If research
cancers that are detected to the Singapore market by doesn’t change clinical practice,
late,” Yee says. the end of 2018.
Alrik Tan
it’s probably not going to make doing tests at
any difference to patients.” the DxD Hub.

technological know-how, there ASIAN RESEARCH COMING everything is coming together its ideas for diagnostic tools,
is little awareness of how to turn OF AGE AND READY FOR at a time when it’s not just such as the gastric cancer test
that technology into a product. TRANSLATION information we need, but also (see left box) or staging and
“DxD is a high-throughput engine With the acceleration of actionable information,” she says. differentiating liver fibrosis for
to help startups and researchers genomics and technology, Asian Fortunately, Singapore has been better treatment outcomes, in
develop diagnostic tests. Those research as a whole is turning its investing in biomedical research pre-existing A*STAR research.
startups may then later translate attention to translation says Yee. and engineering for many years. “We don’t do discovery of
IP on their own or they can There is currently a market of It will serve them well as clinical any genetic biomarkers or
continue to work with us. So, the 700 million people or more solutions customized for Asian protein biomarkers, instead
DxD Hub will have a multiplier populations become much more our job is to mine what has
effect too.” Yee notes that it is
often not appreciated that IP
“We’re also important to markets. “We were
always developing healthcare
already been done in the
ecosystem,” Yee says.
translation is an industrialized getting more solutions for a global population, The hub also hopes to curate
process that produces regulated information but not really paying attention existing data so that artificial
diagnostics solutions, and to the differences in the different intelligence (AI) is better able to
requires the careful integration on how populations. Now we need deliver personal and multimodal
of biology, engineering and the Asian to look at solutions for Asian healthcare solutions – a process
technology platforms. The hope populations more specifically.” that Yee calls “digital diagnostics”.
is to educate and train people on
phenotype is The idea of personalized “To do digital diagnostics,
how to translate research into unique and medicine like this is not new, we need a lot of correlated and
Opposite: © Ullstein Bild/Getty Images
new commercial products in different...” says Yee, but it’s only now curated data. It would take us
companies all over Singapore, possible because technologies years to gather the data if we
she says. in Asia who are starting to like deep learning are converging started from zero. So, we’re
While the DxD Hub is led by spend as much, if not more, with genomics. looking back at what we’ve
A*STAR’s ETPL, it is a nationally per head on medicine as their The DxD Hub is very already done.” Over the last few
funded program and many of its western counterparts. “We’re well placed geographically decades, Yee says, Singapore
projects also come from external also getting more information to use existing Asian data to has invested heavily in medical
parties. Oncology diagnostics is on how the Asian phenotype look for these solutions and research. “Now is the time to
currently its biggest portfolio, is unique and different, and so has already found some of harvest tangible results.”
followed by cardiovascular and
infectious diseases, metabolic
diseases and neurological
disorders. Currently, the
hub is actively working on
25 diagnostic projects.
Opposite: © Courtesy ETPL
The DxD Hub is careful to

keep their attrition rates in line
with industry and select the
right projects. The hub is in the
preliminary stages of assessing
over 400 different projects,
with a projected attrition rate
© This page: Anthony Kwan/Bloomberg via Getty Images
of approximately 90 to 95 per
cent. That’s roughly the same as
commercial industry, Yee says. Of
these 400, they will identify 150 Many researchers
are looking into
that have the evidence to answer
liquid biopsies,
specific diagnostic questions, which detect
which will then be examined DNA and RNA
fragments in the
from a business development
blood. These can
standpoint. At any one time, DxD be used to more
Hub will be in discussions with easily diagnose
cancers.
potential business partners on 40
to 50 of the projects.

A*STAR researchers
discover a protein
duo that helps
chromosomes in
reproductive cells
find each other.
© xxxxxxxxxxxxxx

— SUN1 — which locks on

to the ends of chromosomes
inside the nucleus. With
SUN1 and KASH5 attached,
MOLECULAR the chromosomes inside the
BIOLOGY nucleus would get dragged along
the microtubule scaffolding
randomly, allowing for the
chromosomes to bump into
their homologs.
For this paper, Burke
teamed up with scientists at
CHROMOSOMES the University of Oklahoma to

confirm the theory.
FIND THE PERFECT The team stained the
MATCH DNA in living sperm precursor

cells from normal mice and
mice lacking KASH5, and
A protein duo ensures that the
imaged the cells’ chromosome
chromosomes in reproductive movements in three dimensions.
cells find their significant other. Specialized algorithms revealed
that, unlike normal cells, the
chromosomes stop moving
when KASH5 is lacking, which
Reproduction is made easier can lead to a variety of confirms the team’s model. “This
by finding the right partner inherited disorders. was really gratifying to see,”
— and it’s no different for In 2013, Brian Burke says Burke.
the chromosomes inside and Colin Stewart from The paper co-authors are
reproductive cells. Now, the A*STAR Institute of now chasing leads on how
an international team of Medical Biology set out to mutations in either KASH5
researchers, including A*STAR discover how chromosomes find or SUN1 could be causing
scientists, has revealed just their match. infertility in humans and are
how chromosomes find their investigating how similar protein
perfect match. duos may be working together to
The tightly-wound ‘‘The whole distribute the nuclei located in
chromosomes that carry system is far more other cell types, such as skeletal
the genetic code inside living dynamic than one muscle cell.
cells may float around the would appreciate “We have to stop thinking
cell nucleus on their own, from reading of the nuclear envelope as
but they all have a genetically your average cell just sort of a bag for genes
similar partner, or homolog, biology textbook!’’ which just sit there and do
with one inherited from nothing but be transcribed,”
each parent. says Burke. “The whole system
During the life cycle They revealed that a is far more dynamic than
of reproductive cells, these protein called KASH5 acts as one would appreciate from
homologs need to find and an adaptor for a molecular reading your average cell
© SCIEPRO/Science Photo Library/Getty
dock to each other to ensure motor which shuffles along biology textbook!”
that the DNA is correctly the microtubule scaffolding of
distributed to the sperm the cell. Mice modified to lack 1. Lee, C.-Y., Horn, H. F., Stewart, C. L.,
Burke, B., Bolcun-Filas, E. et al.
or egg: a bad chromosome KASH5 were infertile.
Mechanism and regulation of
match can render the entire The scientists proposed
rapid telomere prophase
cell non-functional. Even that KASH5 docks to the movements in mouse meiotic
worse, failure to distribute surface of the nucleus and chromosomes. Cell Reports 11,
chromosomes correctly teams up with another protein 551-563 (2015).

A leading cause of glaucoma the ocular nerves and tissues.

and blindness is exfoliation The team conducted
syndrome, or XFS, an age-related deep-sequencing analysis of
disorder that results in excess both LOXL1 and CACNA1A in
GLAUCOMA fibrous material building up. samples from 5,570 XFS cases
Now, A*STAR scientists, along and 6,279 healthy controls
with an international research from nine countries. Many of
team, have found a novel the participants were Japanese,
mutation on the LOXL1 gene and it was within this specific
that appears to protect against population that Khor’s team
XFS and glaucoma, alongside five found a rare, protective mutation
new locations on a chromosome in the healthy control group;
EYES OPEN TO associated with XFS1. the p.407F allele, located at the
LOXL1 gene.
A PROTECTIVE ‘‘This mutation
“This mutation has never
MUTATION has never been

been seen before, and it goes
some way to explain why some
seen before, and people appear to be resistant
A genetic mutation that protects
it goes some way to XFS’ effects,” says Khor.
against glaucoma has been to explain why “Although aging ‘loads the
uncovered during an international some people gun’ by inducing cell damage
study into exfoliation syndrome. appear to be and potentially triggering the
resistant to XFS’ exfoliative process, the presence
effects.’’ of the p.407F allele seems to
markedly increase ECM material,
and cells with the mutation bind
“We started a large-scale, together more strongly, delaying
international study of XFS in the progress of the disease.”
November 2012,” explains Chiea The mutation at LOXL1
Chuen Khor at the A*STAR considerably reduces the chances
Genome Institute of Singapore, of developing glaucoma, and
who led the research. “Despite represents a promising target
the large sample size on this for future therapies to treat this
first project, we could only widespread, debilitating condition.
identify one other gene locus “If we can stop cells
(CACNA1A) consistently from exfoliating, we may prevent
associated with XFS to the disease from occurring,”
add to the known locus, says Khor. “The data gives us clues
LOXL1. XFS could not be as to how we might target LOXL1
explained by just LOXL1 and to try to make this happen.”
CACNA1A. There had to be Khor’s team also performed
more biological determinants.” a genome-wide association
As the body ages, study on a larger cohort from 24
molecules that provide countries, uncovering five new
both physical structure and genetic loci associated with XFS
biochemical support to all susceptibility, which they will
tissues and organs — the so- investigate soon.
called ‘extracellular matrix’, or
ECM — can begin to decline, 1. Aung, T., Ozaki, M., Lee, M. C.,
Schlötzer-Schrehardt, U.,
resulting in abnormalities and the Thorleifsson, G. et al. Genetic
© Purestock/Getty
development of XFS. In XFS, cells association study of exfoliation syn-

are torn, or ‘exfoliated’, from the drome identifies a protective rare
A*STAR researchers, together with an international team of scientists, uncover a variant at LOXL1 and five new sus-
rare, protective mutation that appears to prevent glaucoma and the progression of ECM; this is most prominent in ceptibility loci. Nature Genetics 49,
exfoliation syndrome. the eye, and can severely damage 993–1004 (2017).

FAST FLOW
TO SAFETY
CYBER
FORENSICS A new data structure developed
at A*STAR allows rapid tracking
and policing of data flowing in
and out of a network.
signify a stronger creature than

the Cuckoo and Peacock as it
outperforms both tables.
REX works by exploiting
some inherent characteristics of
internet traffic. For example, it
takes into account the ‘heavy-
tail’ behavior of data flows (there
are a few large ‘elephant flows’
which contribute to a larger
percentage of the total volume
than the many small ‘mice
flows’), by employing a hierarchy
of sub-tables increasing in
size from top to bottom. This
structure effectively segregates
the different types of flows.
“We also utilized the special
processing property of computer
RAM,” says Thing. “Our design
features both fast, expensive
The way that network traffic is tracked has a huge effect on the speed at which it can be analyzed and checked for malicious activities.
The REX data structure developed at A*STAR is faster and more resilient against attacks than previous efforts. Static RAM and slower, cheaper
Dynamic RAM.” The faster
SRAM is used to process the
To protect networks from maps values to specific locations, these hash tables fill up quickly, few large, important flows,
malicious threats, cyber- labeled with indices,” explains eroding performance. allowing fast tracking and
security solutions must track Vrizlynn Thing from A*STAR’s frequent updates, while DRAM
all the data flowing through the Institute for Infocomm Research, handles the low priority flows in
‘‘We also utilized
network — just like security who led the study. “To find a secondary sub-tables.
guards checking travelers in value, the hash table performs
the special In tests using real recorded
airports. However, it is hard to computations to quickly identify
processing network traffic, REX was faster
design a solution that works the indices and thus, its location. property of and more efficient at analyzing
fast enough to process all the The challenges are that millions computer RAM.’’ data than Cuckoo and Peacock.
information in real time, and of values need to be stored, and “We will further investigate
to block threats before they can the values are generated and The new data structure the efficiency and scalability
strike. Now, A*STAR researchers transmitted extremely quickly.” developed by Thing and her of this new data structure for
have designed a way to structure Traditional hash tables are team is called REX. “The name security analysis in larger scale
© Appu Shaji/EyeEm/Getty
data that is robust against becoming inefficient as the REX stands for Resilient and environments,” says Thing.
cyber-attacks and allows it to be internet grows and data flows Efficient data Structure (X for
processed in record time. get larger. Researchers have structure)” says Thing. Jokingly, 1. Divakaran, D. M., Ko, L. L., Su, L. &
Thing, V. L. L. REX: Resilient and
The team’s work improves developed data structures known Thing explained that this data efficient data structure for tracking
on widely-used data structures as Cuckoo and Peacock, but structure was named REX network flows. Computer Networks
called ‘hash tables’. “A hash table when they are under attack, (after Tyrannosaurus Rex) to 118, 37–53 (2017).

CONTENTS | F E AT U R E S | RESEARCH HIGHLIGHTS | IMAGE HIGHLIGHT
A HAIR-RAISING
IMAGE
To investigate the role of cellular
senescence in age-related hair
depigmentation, the loss of lamin
B1 is employed as a biomarker to
detect senescent cells in hair follicles.
Immunofluorescent image of a human
© 2017 A*STAR Institute of Medical Biology
hair bulb stained with lamin B1 (green),

keratin 15 (red, denotes keratinocytes)
and c-kit (gray, denotes melanocytes).
This project is a research collaboration
between Oliver Dreesen and Carlos
Clavel at the Institute of Medical Biology.
(Image by Audrey Wang)

HUMAN
GENETICS
WHAT MAKES
BRAINS GROW
SMOOTH AND
SMALL?
Researchers uncover how
a microtubule-related gene
affects neural development.
The mechanism linking mechanism linking P80 to as a motor to shuffle between that P80 and NuMA activity in
cortical developmental disorders these symptoms2. the nucleus and the centrosome, the centrosome is essential for
with a gene related to key The study began with a a microtubule organizing neural development. In mouse
structural components of cells search for proteins that interact center that plays a crucial embryos, neurons lacking
known as microtubules has with P80. To the researchers’ role in mitosis. The lack of either protein differentiated
been uncovered by A*STAR surprise, they discovered an either protein led to abnormal early, divided insufficiently, and
scientists. The discovery interaction with NuMA, a mitosis. Mutations in P80 migrated abnormally.
improves our understanding of well-studied protein which linked with microlissencephaly “With each gene causing a
the pathology of the disorders organizes microtubules impaired its interaction with similar phenotype, we are adding
and expands the range of during mitosis. They also dynein or with microtubules, more pieces to the puzzle. By
genes known to be involved confirmed that P80 binds to suggesting that the P80-NuMA- connecting the dots we will
in neurodevelopment. dynein, a molecular motor dynein network plays a role in eventually get the big picture of
Microcephaly and associated with microtubules these disorders. how a human brain is built,” says
lissencephaly are disorders in that had already been identified “The most elegant assay Reversade. In the meantime, each
which brains develop to be as a P80 partner. we did was the in vitro aster gene they identify improves the
abnormally small or abnormally formation,” says Oz Pomp, a prospects of genetic counseling
smooth, respectively. In 2014, ‘‘With each gene scientist in the Reversade lab who and screening and provides a new
Bruno Reversade’s team at the co-led this project. Asters are avenue for researchers studying
causing a similar
A*STAR Institute of Medical microtubule arrays formed during brain disorders.
phenotype, we
Biology and Chris Walsh’s mitosis around the centrosome,
lab at Harvard showed that
are adding more an organelle which forms 1. Hu, W. F., Pomp, O., Ben-Omran, T.,
patients with both disorders pieces to the microtubules and regulates the Kodani, A., Henke, K. et al. Katanin
— microlissencephaly — carry puzzle.’’ cell cycle, and Pomp was amazed

p80 regulates human cortical
development by limiting centriole
a mutated version of the P80 to find that combining P80, and cilia number. Neuron 84,
gene, which encodes a subunit The researchers then NuMA, dynein, microtubules, 1240–1257 (2014).
of the KATNB1 gene1. In a investigated how these proteins and the energy-storage molecule 2. Jin, M., Pomp, O., Shinoda, T., Toba, S.,
Torisawa, T. et al. Katanin p80, NuMA
follow-up paper, the Reversade regulate microtubules during ATP in a test tube was enough for and cytoplasmic dynein cooperate
lab and their collaborators mitosis. They showed that asters to form. to control microtubule dynamics.
in Japan have uncovered the P80 and NuMA use dynein Finally, the team showed Scientific Reports 7, 39902 (2017).

A vaccine candidate that blocks an intentionally mutated version

infection and confers protection of the antibody that stops
against all four strains of dengue antibody−virus complexes from
virus has been uncovered by entering cells, thereby preventing
VACCINES Katja Fink and Cheng-I Wang enhancement of dengue
from the A*STAR Singapore infection. This phenomenon
Immunology Network, in known as ‘antibody-dependent
collaboration with colleagues enhancement’ helps to explain
from across Singapore. why patients who have been
The mosquito-borne dengue infected by dengue before
virus currently has no specific are more likely to experience
vaccine or treatment. Originally severe symptoms when they
A DENGUE confined to Southeast Asia, the

dengue virus has now spread
are infected subsequently by
a different serotype. This is a
TREATMENT THAT to southern China, Africa, major barrier for developing
IS ONE ‘FOUR’ ALL Indonesia, Australasia, Latin

America and the United States.
therapeutic antibodies against
dengue virus.
An antibody that targets all Millions of people are infected
by the virus each year and ‘‘The key to this
four strains of the virus renews usually develop mild flu-like cross-reactivity
hope for effectively treating symptoms and a characteristic lies in the unique
and preventing dengue. skin rash. However, around one virus−antibody
in every thousand cases is fatal binding site.’’
due to dengue hemorrhagic fever
or dengue shock syndrome. Fink concedes that they were
The development of a safe surprised at the efficiency of
An antibody
(pictured) called and effective small molecule SIgN-3C-LALA against all four
SIgN-3C-LALA drug or vaccine against dengue dengue serotypes. “Usually, very
protects against has been elusive, partly due potent neutralizing antibodies
all four serotypes
to the complexity of the virus are specific against one virus
of dengue virus.
itself. There are four strains or serotype, [while] cross-reactive
‘serotypes’ and each produces antibodies are usually less
different immune responses potent” she explains. The key to
by interacting with antibodies this cross-reactivity lies in the
in human blood serum. Fink‘s unique virus−antibody binding
team have been working to site. SIgN-3C-LALA targets a
develop a therapeutic agent that site that is conserved across
is effectively a combination of serotypes and is crucial for
four treatments. virus integrity.
Their first step was to isolate With a grant from the Global
an antibody (SIgN-3C) produced Health Innovative Technology
by a naturally-infected dengue Fund, the team continues to
© PIXOLOGICSTUDIO/SCIENCE PHOTO LIBRARY/Getty
patient that is able to bind to investigate the mechanism

all four dengue virus serotypes of action of the antibody and
and prevent their replication are working with Chugai
in cells. When administered to Pharmaceuticals to evaluate its
mice, SIgN-3C reduced blood- suitability for the treatment of
virus levels after exposure dengue in humans.
to any of the four dengue
serotypes. If administered before 1. Xu, M., Zuest, R., Velumani, S.,
Tukijan, F., Toh, Y. X. et al. A potent
exposure, it conferred protection
neutralizing antibody with therapeu-
against infection. tic potential against all four sero-
Similar findings were types of dengue virus. npj Vaccines
reported with SIgN-3C-LALA, 2, Article number: 2 (2017).

Transparent flexible
electronics based
on 2D materials.
MATERIALS
PRODUCING
TOP-NOTCH
2D MATERIALS
Mass producing
ultrathin nanosheets
could lead to next-
generation electronic and
optoelectronic devices.
Molybdenum trioxide (MoO3)

has potential as an important
two-dimensional (2D) material,
but its bulk manufacture has
lagged behind that of others have sought to develop a simple Celsius without the need for a growth and exfoliation techniques
in its class. Now, researchers technique for mass producing specific substrate. developed by the team could
at A*STAR have developed large, high-quality nanosheets “In general, crystal growth at also be helpful in manipulating
a simple method for mass of MoO3 that are flexible elevated temperatures is affected the band gap — and therefore
producing ultrathin, high-quality and transparent. by the substrate,” explains Liu. the optoelectronic properties
MoO3 nanosheets.1 “Atomically thin nanosheets “However, in the absence of an — of 2D materials by forming
Following the discovery of of molybdenum trioxide have intentional substrate we could 2D heterojunctions, interfaces
graphene, other 2D materials novel properties that can be better control the crystal growth, between two layers of different
such as transition metal di- utilized in a range of electronic allowing us to grow molybdenum materials.
chalcogenides, began to attract applications,” says Liu. “But trioxide crystals of high purity “We are now attempting
considerable attention. In to produce good quality and quality.” to fabricate 2D molybdenum
© 2017 A*STAR Institute of Materials Research and Engineering
particular, MoO3 emerged as an nanosheets, the parent crystal After cooling the crystals trioxidenanosheets with larger
important 2D semiconducting must be of very high purity.” to room temperature, the team areas, as well as exploring their
material because of its By first using a technique used mechanical and aqueous potential use in other devices,
remarkable electronic and optical called thermal vapor transport, exfoliation to produce submicron- such as gas sensors,” says Liu.
properties that hold promise for the researchers evaporated thick belts of MoO3 crystals.
a range of new applications in MoO3 powder in a tube- Once they subjected the belts to 1. Liu, H., Cai, Y., Han, M., Guo, S., Lin,
M. et al. Aqueous and mechanical
electronics, optoelectronics and furnace at 1,000 degrees sonication and centrifugation, exfoliation, unique properties and
electrochromics. Celsuis. Then, by reducing the they were able to produce large, theoretical understanding of MoO3
Liu Hongfei and colleagues number of nucleation sites, high-quality MoO3 nanosheets. nanosheets from free standing
from the A*STAR Institute they could better match the The work has provided a-MoO3 crystals: Raman mode
softening and absorption edge blue
of Materials Research and thermodynamic crystallization new insights into the interlayer shift. Nano Research advance online
Engineering and Institute of of MoO3, to produce high- electronic interactions of 2D publication, 10 August 2017 (doi:
High Performance Computing quality crystals at 600 degrees MoO3 nanosheets. The crystal 10.1007/s12274-017-1733-x).

looked at how the child’s size

at four years related to this
combined score.
The team found that the
OBESITY more risk factors a family had,
the more likely their child was
to be overweight or obese.
Surprisingly, the weights of
both parents made an equal
contribution. “If either the mum
or the dad was overweight, the
contribution was similar, but if
LIKE FATHER both parents were overweight,

the probability of the child being
LIKE CHILD overweight doubled,” says Aris.
FOR WEIGHT GAIN Compared to children whose

families had no risk factors,
A father’s weight is just as those with four or more risk
factors were 11 times more likely
relevant as the mother’s in to be overweight. Parents’ weight
determining a child’s risk made the greatest contribution
of obesity. to a child’s obesity risk, followed
by pregnancy weight gain,
breastfeeding duration, timing
of solid food introduction, and
It’s not only women who have higher blood sugar levels maternal glucose levels.
should be concerned about during pregnancy, which in turn The researchers note
the impact of their weight on could cause the fetus to gain that while fathers could
their children’s health. A*STAR more weight. be transmitting genetic, or
researchers have identified a set epigenetic factors that influence
of factors, including the father’s obesity risk, their weight
weight, that combine to increase ‘‘The most could also be a more general
a child’s risk of obesity up to important thing indicator of family diet and
11-fold1. is that all these exercise levels.
The period between risk factors are “The most important thing
conception and a child’s modifiable.’’ is that all these risk factors are
second birthday is crucial modifiable,” says Aris. “Targeting
in determining his or her only one of them will have a
future risk of obesity. Previous To investigate these limited impact, but if we can
studies have identified several relationships in more detail, target them in tandem then we
factors that can boost obesity Aris and his colleagues should be able to reduce the
risk during this window, but assessed 1,247 women during risk of obesity even further.”
most only considered them pregnancy and when their Advice and support could also be
in isolation. “Few studies children were four years old, directed at families where many
have looked at how risk scoring them against the of these factors are present.
factors combine to influence following criteria: mother
a child’s risk of obesity, which overweight/obese; father 1. Aris, I. M., Bernard, J. Y., Chen, L. W.,
Tint, M. T., Lee, Y. S., et al. Modifiable
is important because many overweight/obese; excessive
risk factors in the first 1000
of them are interlinked,” says weight gain during pregnancy;
© ozgurdonmaz/E+/Getty
days for subsequent risk of

Izzuddin Bin Mohd Aris raised blood glucose childhood overweight in an Asian
© xxxxxxxxxxxxxx
of the A*STAR Singapore during pregnancy; breastfeeding cohort: Significance of parental

overweight status. International
Institute for Clinical Sciences. for less than four months;
Journal of Obesity advance online
For example, if the mother is and introducing solid food publication, 28 July 2017 (doi:
overweight, she’s more likely to before four months. They also 10.1038/ijo.2017.178).

Dad’s weight
contributes to a
child’s risk of obesity.
© xxxxxxxxxxxxxx

THERAPEUTICS
MAKING HIV
DRUGS WORK
LONGER
Computational
modeling of drug Computational mod-
eling suggests that
resistance could a HIV drug called
lopinavir (pictured)
help guide treatment should be used
decisions for people before others of the
same type to avoid
infected with HIV. cross-resistance.
A bioinformatic examination The team modeled the protease inhibitor would probably should try one of the four
of HIV mutations could structures of more than induce resistance to lopinavir other protease inhibitors that
help guide the selection of two dozen mutated proteases as well. That means it’s not are prone to cross-resistance,
antiretroviral therapies in that clinicians found made very useful if taken by patients while saving the two that are
such a way that the onset HIV resistant to any one of after other drugs have started to least affected by cross-resistance
of drug resistance could be seven different protease-blocking fail. However, since resistance as agents of last-resort.
delayed. This would “prolong drugs. These mutations arose to lopinavir does not seem Clinical implementation
drug effectiveness, improve in patients who were taking to affect how well the other of these recommendations
quality of life and lower just one of these drugs, but six protease inhibitors will will be needed to test the
treatment costs,” says Samuel they impacted the efficacy of work, Gan and Su conclude predictions of the computational
Ken-En Gan, from the A*STAR other protease inhibitors, too. that lopinavir should be modeling. But as Gan notes,
Bioinformatics Institute. The A*STAR team showed that considered as the drug of choice the insights gleaned from
Through structural modeling cross-resistance can develop for patients who are getting their his group’s structural analysis
and computational analyses, Gan easily across five of the seven first protease inhibitor. would be hard to come
and his team have shown how protease inhibitors, but less so for by any other way. “This paper,”
changes in the HIV genome that the other two. he says, “represents a landmark
make the virus resistant to one That kind of information, ‘‘These drugs analysis using bioinformatics
© LAGUNA DESIGN/Science Photo Library/Getty
antiretroviral drug can often says Chinh Tran-To Su, impacted the to go where experimental
induce resistance more broadly a postdoctoral fellow in labs and clinical trials cannot
efficacy of
to other drugs of the same class. Gan’s lab, “could help guide easily investigate.”
other protease
The findings suggest that some of the selection of drugs for the
these drugs should be prescribed first and subsequent lines
inhibitors, too.’’ 1. Su, C. T., Ling, W. L., Lua, W. H.,
Haw, Y. X. & Gan, S. K. Structural
before others. This includes of treatment.” analyses of 2015-updated
drugs that block critical viral Take the protease drug-resistant mutations in
proteases — enzymes that break inhibitor lopinavir, for Should resistance then HIV-1 protease: an implication
of protease inhibitor cross-
down proteins — called protease example. The analysis found emerge to lopinavir, the resistance. BMC Bioinformatics 17,
inhibitors. that resistance to any other analysis indicates that patients 500 (2016).

BUILDING A
BARRIER AGAINST
TWO-
DIMENSIONAL OXIDATION
MATERIALS
Chemically stabilizing atomically
flat materials improves their
potential for commercial application.
Two-dimensional materials have created single layers of other Computing used first-principles in air is the absorption of
could underpin a novel family materials — tin, germanium, calculations to demonstrate oxygen. The fast oxidation of
of flexible, low-power electronic boron, silicon and phosphorus that placing phosphorene on a freestanding phosphorene in
devices, but their success — with their own signature molybdenum diselenide substrate ambient conditions is due to a
depends on ensuring the layers properties. For example, while and applying a vertical electric low energy barrier for oxygen
are chemically stable. A*STAR graphene is a semi-metal without field can drastically increase its absorption of about 0.57
researchers now show that one a band gap, phosphorene is a resistance to oxidation. electronvolts: oxidation can
2D material, phosphorene, can be semiconductor like silicon, which “The interaction and charge occur in less than a minute.
stabilized with the right choice of makes it useful for electronic transfer between substrate and When this analysis is repeated
substrate and an electric field. devices. However, phosphorene phosphorene can be tuned with phosphorene overlying
Graphene, a single layer has a notorious drawback: the by an external electric field, molybdenum diselenide, the
of carbon atoms, deserves its material oxidizes in air and its causing a change in surface activity energy barrier is much higher.
reputation as a supermaterial; quality is rapidly degraded. and suppressing the oxidation of The model also shows that the
it’s strong, hard, light, and has In search of a viable approach phosphorene,” explains Gao. presence of the molybdenum
excellent electronic and thermal to overcome this, Junfeng Gao Their study shows that the diselenide substrate enables more
properties. It is the archetypal 2D and colleagues from the A*STAR dominant process involved in effective tuning of the properties
material. More recently scientists Institute of High Performance the degradation of phosphorene of the phosphorene with an
electric field. This increases
the oxidation energy barrier
even further. Under a suitable
vertical electric field, the
barrier can increase to 0.91
electronvolts. This lifetime
of the phosphorene against
oxidation can be 105 times greater
than that without treatment.
Gao’s approach
to achieve air-stable
phosphorene may greatly
promote its use in practical
© 2017 A*STAR Institute of High Performance Computing
devices. “We will explore more

substrates for their ability to
stabilize phosphorene,” says
Gao. “In particular, we want
to find out if such a substrate
is suitable for epitaxial growth
of phosphorene.”
1. Gao, J., Zhang, G & Zhang, Y.,-W.

Vastly enhancing the chemical
stability of phosphorene by
The absorption of oxygen (red) damages phosphorene (purple, top), but the phosphorene is protected when on a molybdenum diselenide employing an electric field.
substrate (bottom). Nanoscale 9, 4219 (2017).

The majority of cyber security Infocomm Research, who led

solutions that stand between us the study.
and increasingly sophisticated Thing and her team designed
malware target only specific their new framework to look out
CYBER attacks or subsets of attacks, for the fundamental character-
DEFENSE meaning that users may have to istics of the malicious activities
buy and install many different that stalk unsuspecting users
products to protect themselves. through the evolving cyber land-
Now, A*STAR researchers have scape. Through this approach,
developed a system that instead the framework is robust against
gathers evidence across a wide new threatening software and
stream of internet traffic and gathers only relevant evidence
SEEING identifies links and correlations

related to suspicious activity1.
on the threats. For example,
the system looks out for data
THE BIG PICTURE “Our aim is to develop a flows that arrive at fixed time
framework to gather as much intervals, because attack bots are
A system that identifies evidence as possible from a set much less random than ordinary
malicious patterns in network of traffic and indicate malicious human-generated internet activ-
anomalies, regardless of the type ities. The model also identifies
traffic could help create a
of attacks,” says Vrizlynn Thing sources that try to communicate
more secure internet. from the A*STAR Institute for with a large number of destina-
© ANDRZEJ WOJCICKI/SCIENCE PHOTO LIBRARY/Getty
An A*STAR team
have developed a
system that looks
for general patterns
associated with
suspicious activities
in network traffic,
in order to defend
against a wide
variety of threats.

tions in a short time, which is

indicative of a botnet.
“The main challenge was
devising ways to build up a
large set of possible patterns REPRODUCTION
which could serve as potential
evidence for detecting a
wide variety of anomalies,”
says Thing. “We capture the
persistent characteristics of
the malicious activities in
transit, and represent them in
observable sequential forms.
This has allowed us to detect
A PROTEIN TO
very fundamental patterns MAKE SPERM
related to malicious traffic.”
A protein essential
‘‘We could for spermatogenesis
© DAVID MACK/Getty images

trigger the may help combat
disconnection of male infertility and
infected hosts,
curbing the lead to new methods
rampant growth of contraception.
of botnets.’’
The team tested their new “Infertility is generally of Molecular and Cell “The next step is to figure
evidence-gathering system on perceived to be mostly a female Biology and collaborators out all of the functions of Emi2
recorded internet traffic, and problem, but this is wrong,” elsewhere in Singapore and in making sperm,” says Kaldis.
found it could quickly identify says Philipp Kaldis, researcher in Taiwan, the USA and The work so far suggests that
many notorious botnets such from A*STAR. Kaldis studies Europe1. They say this indicates it is essential, but has not fully
as Andromeda, Zeus and Sality, the development of human that the protein may play revealed why.
with very few false positives. sperm, his work could one a similar role in humans. There are hints,
Given this success, Thing is day lead to the treatment The researchers were able to however, from the protein’s
hopeful that by improving of male infertility and help identify the crucial role for known role in the ovary.
their detection patterns, their develop chemical contraception Emi2 in testes by creating There, it regulates meiosis, an
system could defend networks methods for males. mice in which the gene that essential cellular process for
against a much wider variety To set his work in context, codes for the protein was halving chromosome numbers
of attacks than has previously Kaldis points to studies knocked out. The mice were left to make egg and sperm cells that
been possible. reporting a 50-60 per cent sterile, but suffered no other will combine to form a fertilized
“If we can detect malware fall in sperm counts between major effects. egg cell.
infections by analyzing net- 1973 and 2011. “Claims that “Nobody had previously Any applications of
work traffic, we can prevent this trend could lead to the studied the role of this the research to devise
malware from further spread- extinction of the human protein in testes,” says treatments for male infertility,
ing,” she says. “We could also race may be exaggerated,” he Kaldis, noting that the or contraceptives, would
trigger the disconnection concedes, but they do indicate protein has been shown to be require much further
of infected hosts, thereby a need for understanding involved in controlling the research, but Kaldis’ work
curbing the rampant growth male fertility. cell divisions that produce lays the foundations for major
of botnets.” The importance of a egg cells in ovaries, but that medical advances.
protein called Emi2 for its activity has not been
1. Divakaran, D. M., Fok, K. W., generating sperm in mice has detected in other tissues. 1. Gopinathan, L., Szmyd, R., Low, D.,
Nevat, I. & Thing, V. L. L. Diril, M. K., Chang, H-Y. et al.
now been shown by Kaldis, This all suggests that it
Evidence gathering for network Emi2 is essential for mouse
security and forensics. Digital working with colleagues is an important player in spermatogenesis. Cell Reports 20,
Investigation 20, S56–S65 (2017). at the A*STAR Institute human reproduction. 697–708 (2017).

POLYMERS ARE
TOUGH ON MICROBES,
ANTIMICROBIALS SOFT ON SKIN
Polymers that kill germs rapidly
and effectively will help in the fight
against multidrug-resistant microbes.
Inexpensive antimicrobial drug-resistant microbes. The polymers with optimized scrubs, hand washes and
polymers that are gentle on the The antimicrobial compounds structures killed almost 100 disinfectants,” she adds.
skin and highly effective in killing of the body’s immune system use per cent of microbes within The polymers have two
microbes have been developed by a different tactic — they fight two minutes. They were also key components: positive
A*STAR researchers1. They have microbes by destroying their softer on the skin of mice than charges and hydrophobic
promise for use in surgical scrubs membranes. Since this approach commercial surgical scrubs parts. Their positively charged
and disinfectants. is based on the inherent electrical that are currently used in components interact with the
Most antibiotics work properties of the cell membrane, it clinical settings. negatively charged membranes
by disrupting the specific is much harder, if not impossible, “Our polymers kill a broad of pathogenic microbes, while
biochemical pathways microbes for microbes to develop resistance. spectrum of microbes, especially the hydrophobic parts of the
use to make the proteins and Now, Yi Yan Yang the difficult-to-kill Pseudomonas polymers enter the two layers
enzymes which are essential for of the A*STAR Institute aeruginosa, faster than any of of fat cells inside membranes.
their survival. This strategy makes of Bioengineering and the many antimicrobial peptides This double action ruptures
them lethal to microbes but safe Nanotechnology and her and polymers reported to the membrane and destroys
to the cells of humans and other co-workers, in collaboration date,” comments Yang. “With the microbe. Since the surfaces
mammals. However, it is easy for with IBM Almaden Research their superfast bactericidal of mammalian cells are less
microbes to develop resistance to Center, have developed powerful effect and skin compatibility, negatively charged than those
such antibiotics, which has led to antimicrobial polymers that these polymers are promising of microbes, cells such as red
the widespread problem of multi employ the same strategy. candidates for use as surgical blood cells are immune to the
polymers’ action.
The researchers found that
repeated use of the polymer at
sub-lethal doses did not lead to
bacterial resistance. In addition,
the polymers are inexpensive
to make and can be synthesized
from commercially available
starting materials.
“Building on this work, we are
developing biodegradable versions
of the polymers,” says Yang. “They
are designed to degrade into
benign, environmentally-friendly
compounds. Such biodegradable
© MARK THOMAS/SCIENCE PHOTO LIBRARY
antimicrobial polymers may be

A surgical team used as preservatives in cosmetics
‘scrubbing up’ in and even food products.”
preparation for
surgery. Researchers
1. Liu, S., Ono, R. J., Wu, H., Teo, J. Y.,
at A*STAR have
Liang, Z. C. et al. Highly potent anti-
developed antimicro-
microbial polyionenes with rapid
bial polymers that are
killing kinetics, skin biocompatibility
promising for use as
and in vivo bactericidal activity.
surgical scrubs.
Biomaterials 127, 36–48 (2017).

Electronic
microscopy
images of pre-
DCs (top) and
IMMUNE pDCs (bottom).
SYSTEM
2µm 2µm
UNRAVELING
THE COMPLEXITY
Powerful new technologies
shed light on the origin and
maturation process of key
immune system cells.
2µm 2µm
The accuracy of previous from the A*STAR Singapore rely on prior knowledge, to with pDCs, but that are
immunology studies has been Immunology Network, who re-examine the classification functionally distinct as they are
called into question by the led the international team and interrelationship of able to mature into cDC1 and
discovery of an additional cell of researchers. dendritic cells. cDC2 cell types but not pDCs.
subtype. The comprehensive There are two main “We were amazed to find this
analysis of the maturation types of dendritic cells: cluster of cells with unique
process of the immune system’s plasmacytoid DCs (pDCs)
‘‘We were properties that lie between
dendritic cells could lead to new (see image), which promote
amazed to find those of pre-DCs and pDCs”
potential targets for more antiviral immune responses this cluster of says Ginhoux.
effective immunotherapy through the production of cells with unique These findings bring
treatments and vaccines. interferons, and conventional properties into question results from
Pathogens such as DCs (cDCs). The latter between those many studies that have relied
bacteria and viruses trigger come in two flavors or subsets: of dendritic cell on a small set of markers
an immediate, nonspecific cDC-1 and cDC-2 and have precursors and to isolate pDCs. “It is likely
immune response. Dendritic crucial roles in mounting plasmacytoid that such studies were
cells are immune system cells immune responses to dendritic cells.’’ contaminated with pre-DCs”
that ‘decide’ whether to mount intracellular and extracellular Ginhoux explains.
a longer, specific and more pathogens, respectively. Further analyses confirmed
complex immune response that However, little is known They applied two powerful previous findings in mice
will protect against subsequent about the origin of dendritic cells technologies: single-cell RNA that the pre-DC population
© 2017 A*STAR Singapore Immunology Network
re-infection with the same and the mechanisms through sequencing and cytometry by can be split into pre-cDC1
pathogen. “Characterizing which they become specialized time-of-flight to a fraction of and pre-cDC2 lineages as the
the immune system’s key to carry out these functions. human blood cells containing precursors start to commit to a
decision-making cells is crucial Until now, dendritic cells dendritic cells and dendritic particular lineage.
to improve the efficacy of have been identified and cell precursors (pre-DCs) (see
vaccines and develop better characterized based on the image), and analyzed the entire 1. See, P., Dutertre, C. A., Chen, J.,
Günther, P., McGovern, N. et al.
therapeutics for devastating expression of particular proteins gene expression and protein
Mapping the human DC lineage
autoimmune diseases such as or surface markers. Ginhoux profile of these cells. through the integration of
multiple sclerosis or lupus” and colleagues took a different They identified pre-DCs high-dimensional techniques.
explains Florent Ginhoux, approach, which does not that share surface markers Science 356, eaag3009 (2017).

or interface layer that sits

underneath the CZTS, helping to
collect electrical charge.
A technique called
MATERIALS quaternary sputtering was used
to grow thin films of CZTS,
where a single target made from
CZTS was used as a source for
depositing the film. This method
offers several advantages over
other deposition methods,
including excellent uniformity
A SPUTTERING STEP over large areas and reduced

reliance on toxic precursors. The
CLOSER TO CHEAPER researchers then investigated
SOLAR CELLS the effect of sulfurization

temperature on the formation of
A simple, low cost technique that a molybdenum sulfide (MoSx)
interfacial layer.
uses common materials could lead “The composition and
to significantly cheaper solar cells. structural properties of
the CZTS layer depend on
the deposition process and
the sulfurization,” explains
In the search for alternatives available materials that are Dalapati. “By using a single-
to silicon-based solar cells, cheaper than silicon to process. step sputtering target we were
A*STAR researchers are “CZTS is a semiconducting able to produce a thin film with
investigating a new material compound with a higher a uniform composition and
that is cheaper and easier to absorption coefficient than smooth surface, which limits the
make, and could lead to better silicon,” says Dalapati, “so it’s formation of defects, and is a
performing solar cells.1 able to absorb more visible light highly reproducible process.”
Silicon solar cells are highly and produce more electricity The researchers found that
efficient, converting up to 25 per than silicon, and can be used for the amount of molybdenum
cent of sunlight into electricity, very large-scale applications, like lost, referred to as out-diffusing,
but fabricating the silicon wafers, roofs and solar farms.” during the MoSx layer formation
which need to be around 300 varied significantly with changes
microns thick to absorb all the in sulfurization temperature, and
‘‘Using a
sunlight that falls on them, is an that the overall efficiency of the
expensive process that requires
single-step solar cell was improved by nearly
temperatures of around 1,200 sputtering target five times when the sulfurization
degrees Celsius. we produced temperature was raised from 500
A cheaper alternative to a thin film to 600 degrees Celsius.
silicon is cadmium telluride; with a uniform “We achieved a solar
composition and
© Colin Anderson/Photographer’s Choice RF/Getty
however, it is highly toxic and efficiency of nearly five per cent,

known to cause cancer. This smooth surface.’’ and are aiming for around 15 per
spurred Goutam Dalapati and cent by investigating a suitable
colleagues from the A*STAR buffer and interface layer,”
Institute of Materials Research Solar cells made from says Dalapati.
& Engineering to investigate a CZTS have potential for up
1. Dalapati, G. K., Zhuk, S., Masudy-
copper-zinc-tin-sulfide (CZTS) to 30 per cent efficiency,
Panah, S., Kushwaha, A., Seng, H. L.
© xxxxxxxxxxxxxx
compound, which offers the but require high-quality, et al. Impact of molybdenum out
optical and electrical properties thin films of CZTS with no diffusion and interface quality on
the performance of sputter grown
required in solar cells, but is impurities, and a suitable CZTS based solar cells. Scientific
made from non-toxic, widely material for the ‘buffer’ Reports 7, 1350 (2017).

A*STAR researchers
develop a technique
that could lead to
significantly cheaper
and better perform-
ing solar cells
© xxxxxxxxxxxxxx

Researchers advise
that pregnant
women should try
to avoid eating too
OBESITY much sugar.
HEAVY LEGACY
OF MUM’S
SWEET TOOTH
The babies of women who
consume carbohydrate-rich
foods during pregnancy have
an altered growth-trajectory.
Babies born to women when they were 26–28 weeks The team found that is a lack of research,” says
who have a sugary diet pregnant about their diet during a woman’s carbohydrate Chen. “It’s also important,
during pregnancy have a that period. intake, particularly the because Asians tend to
higher body mass index, amount of sugar she consumed, have higher risk for diseases
according to a new study by during pregnancy, was such as cardiovascular disease,
Singaporean researchers. ‘‘One of associated with more rapid even at the same BMI.”
Childhood obesity the novelties weight gain and a higher peak Given that high sugar
has steadily increased in of this study is BMI during infancy — even intake during pregnancy
recent decades, and is that it is though it didn’t significantly is already known to
associated with a higher risk performed affect the babies’ birth associate with excessive
of cardiovascular disease on an Asian weight. A high carbohydrate pregnancy weight gain and
and type 2 diabetes in intake was also associated higher risk of gestational
population,
later life. Although there’s with a higher BMI diabetes, Chen says it
where there is
some evidence that gaining when the children were assessed may be prudent for pregnant
substantial amounts of
a lack of at 2, 3 and 4 years of age, women to avoid foods and
weight during pregnancy research.’’ suggesting the effect may beverages high in sugar.
can increase the child’s be long-lasting — although The World Health Organization
obesity risk, little is known Once their babies were follow-up studies are recommends getting no
about how the specific foods born, they were weighed at needed to confirm this. The more than ten per cent of
a woman eats affect her regular intervals to track children in the study are total daily energy intake from
baby’s weight. their growth. The childhood now seven, and continue to free sugars.
© JGI/Jamie Grill/Blend Images/Getty
To investigate, Ling-Wei body mass index (BMI) be monitored. Women’s fat

Chen at the National University curve is characterized by a and protein consumption 1. Chen, L.-W., Aris, I. M.,
Bernard, J. Y., Tint, M.-T., Lee, Y. S.
of Singapore, and his colleagues, peak occurring around 6 had no apparent impact on et al. Associations of maternal
Mary Chong and Yung Seng Lee to 12 months, and previous children’s BMI. macronutrient intake during
at the Singapore Institute for research has shown correlation “One of the novelties pregnancy with infant BMI
peak characteristics and
Clinical Sciences interviewed between a higher peak at of this study is that it is
childhood BMI. The American
1,127 women of Chinese, this age and later adverse performed on an Asian Journal of Clinical Nutrition 105,
Malay or Indian background health outcomes. population, where there 705–713 (2017).

a viable technology, however, fabricated an ultrathin film with

requires the ability to modulate sequential layers of iridium,
these properties and to achieve iron, cobalt, and platinum on a
their electrical detection under silicon substrate.
MATERIALS ambient conditions. Harnessing the large and
This led Anjan opposite signs of the chiral
Soumyanarayanan and magnetic interaction between
colleagues from the A*STAR the iridium-iron and cobalt-
Data Storage Institute and platinum interfaces, referred to
Institute of High Performance as the Dzyaloshinskii-Moriya
Computing, in collaboration interaction, allowed the team
with Nanyang Technological to establish a platform for
UNLOCKING University, Singapore and

Lawrence Berkeley National
nanoscale-sized skyrmions.
And by varying the thickness of
MAGNETIC Laboratory in the United the layers, the team was able to
SKYRMIONS States, to develop an innovative

technique for making
modulate the physical properties,
such as the size, density, and
An innovative technique for making ultrathin films for hosting stability of the skyrmions.
tunable skyrmions. “The platform allows us to
tunable magnetic skyrmions could “Our initial goal was to directly control the magnetic
lead to next-generation memory understand skyrmion formation, interactions that govern
and computing technologies. establish their electrical skyrmion properties by simply
detection, and control their varying the thickness of the
physical properties,” explains constituent layers, and provides
Soumyanarayanan. “We are skyrmion configurations tailored
Magnetic skyrmions offer the Only recently discovered, now examining skyrmions to the specific requirements of a
promise of next-generation skyrmions are tiny structures in nanoscale devices for range of different applications,”
memory and computing tech- that are formed in magnetic their potential as bits in says Soumyanarayanan.
nologies, such as cache memory materials and behave like memory applications.” The work demonstrated,
devices and cloud computing. nanoscale magnetic particles. By using a technique called for the first time, the electrical
Now A*STAR researchers have This means they can self- magnetron sputtering — a detection of ambient
developed an innovative tech- organize into ordered arrays process in which atoms are skyrmions, and could lead
nique for making tunable skyr- or lattices, and can be created, ejected from a source material to stable and highly scalable
mions that could help unlock moved, and erased using and then deposited on to a skyrmion-based memory
their potential.1 electrical currents. To become substrate — the researchers and computing technologies,
explained Soumyanarayanan.
These could then be easily
Schematic array integrated into microchips
of magnetic using existing manufacturing
skyrmions in a processes commonly used in the
uniformly magnetized
background. Arrows
electronics industry.
denote the orientation “Our next steps will be
of magnetic spins to stabilize the skyrmions in
forming the skyrmion
nanostructures at zero magnetic
structures.
field, and to demonstrate their
electrical reading and writing
© 2017 A*STAR Data Storage Institute
in electronic devices,” says

Soumyanarayanan.
1. Soumyanarayanan, A., Raju, M.,

Gonzalez Oyarce, A. L., Tan, A. K. C.,
Im, M. Y. et al. Tunable room-
temperature magnetic skyrmions
in Ir/Fe/Co/Pt multilayers. Nature
Materials 16, 898–904 (2017).

Improving the design of drilling process, it is necessary

drills capable of excavating to understand the coolant
deep holes should increase flow behavior.”
their performance and longevity. Tnay and co-workers started
MACHINE Scientists from A*STAR by experimentally measuring
TOOLS develop a computational the resistance exerted on a chip
model that can determine the falling through a tube filled with
ideal drill design, achieving the cooling fluid. The team then
significant savings. developed their computational
In designing a drill, a fluid dynamics model to recreate
crucial consideration is the the drag coefficients determined
effective removal of material, by these experimental results.
A BIT OF known as chips. A standard

drill bit, the part of the drill
Once they knew the model
worked, the researchers could
PERFECTION that excavates the hole, removes compute the fluid flow and
chips by having a spiral chip transport in gundrills with
The optimum drill geometry shape that carries the chips different geometries.
for creating deep, narrow up the length of the bit and
out of the hole entrance. But
holes is determined using a ‘‘Roughly a
there is a limit to the depth
computational model. that can be reached by spiral 30 per cent
drill bit, usually a distance improvement
between five to ten times the in tool life
bit diameter. is achieved
Computational An alternative approach, compared to
fluid dynamic known as gundrilling, can the current
simulations of a chip
create holes with a depth-to-
falling through a fluid commercial
diameter ratio of more than
enables optimization
three hundred. The unusual
gundrill design.’’
of gundrill design.
shape of the tip of a gundrill
bit gives it a single cutting They considered the overall
edge that enables the drill shape of the tip, referred to as the
bit to self-center and ensures nose grind contour, the number
deep and straight holes. Chips and shape of the coolant flow
in a gundrill are removed holes running inside the drill
by forcing a fluid through bit, and the angle of the cutting
the bit at high pressure. This edge. Their results indicated
fluid also acts as a coolant that the optimum design has a
to prevent damage to both kidney-shaped cooling holes, a
the cutting surface and the zero-degree shoulder angle and
drill bearings. a nose grind contour known
© 2017 A*STAR Singapore Institute of Manufacturing Technology
Guan Leong Tnay from the as N4. “With this optimization

A*STAR Singapore Institute of tool geometry, roughly a 30
of Manufacturing Technology per cent improvement in tool
and colleagues now achieve life is achieved compared to the
this by developing a novel current commercial gundrill
methodology to simulate design,” says Tnay.
gundrill coolant flow based on a
technique called computational 1. Woon, K.S., Tnay, G.L., Rahman, M.,
Wan, S. & Yeo, S.H. A
fluid dynamics. “Gundrill computational fluid dynamics
geometry is complicated; (CFD) model for effective
changing any single parameter coolant application in deep hole
gundrilling. International Journal of
could affect the coolant flow,” Machine Tools & Manufacture 113,
explains Tnay. “To improve the 10–18 (2017).

AUTOIMMUNITY
LUPUS LINK TO
STIMULATORY
PROTEINS Monocytes (pictured), or
white blood cells, play an
essential role in protecting
Lupus patients exhibit us from pathogens, but
altered cell proteins, can also overexpress
excitatory proteins
a discovery with associated with systemic
lupus. It’s yet to be seen
potential implications for whether this overexpres-
diagnostics and studies sion contributes to the
disease, or just indicates
into the disease’s origins. its presence.
Autoimmune diseases such and Cell Biology, recently responses upon recognizing showed no disparity in SLE
as lupus — in which the body discovered a link between SLE the body’s own molecules. disease severity/prevalence
attacks its own cells and tissues and the increased prevalence This is thought to be an innate between those with, or without,
— are on the rise, according to of a cell-surface protein that mechanism that prevents the the gene variant.
A*STAR’s Anna-Marie Fairhurst. modulates immune responses, body from attacking itself. This paper is the first
Her team is the first to observe called ‘Siglec-14.’ Siglec-14, however, differs in to explore the relationship
that patients with lupus exhibit that it’s an excitatory molecule between SLE and monocyte
an increased number of a specific that stimulates host defenses. Siglec expression, and Fairhurst
type of protein on the surface of ‘‘Every discovery “An increased expression hopes that other institutions
certain white blood cells. This in research is a of Siglec-14 would create a will start to look at the
finding may help diagnosticians stepping stone.’’ greater stimulatory signal,” relevance of Siglec proteins to
in detecting the disease, or reveal says Fairhurst. It’s not fully disease: “Every discovery in
new avenues of research into understood how much the research is a stepping stone, and
its causes. The team assessed increased protein contributes to since this study is the first of its
“Systemic lupus 39 patients with SLE and the disease: “The increase could kind, I’d like other researchers
erythematosus, or SLE, is the found that, compared to a either amplify inflammation or to be able to reproduce these
© ROGER HARRIS/SCIENCE PHOTO LIBRARY/Getty
archetypal autoimmune disease, cohort of healthy individuals, just be an indicator of disease,” results, and then build on
and affects the whole body,” says the patient group expressed says Fairhurst. them to find out why this
Fairhurst. Common symptoms significantly more Siglec-14 In a previous study happens, and better understand
include fever, swollen joints, proteins on a class of white blood into Siglec-14 and chronic human disease.”
and fatigue, though the exact cells, called monocytes. SLE obstructive pulmonary
presentation and severity vary disease severity also increased disease, a gene variation causing 1. Thornhill, S. I., Mak, A., Lee, B.,
Lee, H. Y., Poidinger, M. et al.
from patient to patient. in tandem with the monocyte the loss of Siglec-14 expression Monocyte Siglec-14 expression
Fairhurst’s research group, levels of Siglec-14 among the resulted in a reduced risk of is upregulated in patients with
including scientists from the study group. inflammatory response that systemic lupus erythematosus
and correlates with lupus disease
Singapore Immunology Network Most Siglec proteins are could exacerbate the disease. activity. Rheumatology 56,
and the Institute of Molecular inhibitory, dampening immune Fairhurst’s results on SLE 1025–1030 (2017).

An electron
microscopy image
of the KNN thin
film showing
PIEZOELECTRICS the controlled
formation of the
crystalline domains
responsible for the
piezoelectric effect.
LEAVING LEAD
BEHIND
Thin films of a lead-
free piezoelectric
finally match the
performance of the 1µm
lead-bearing standard.
An advance in fabrication applications. However, PZT Now, Kui Yao and colleagues The interactions between the
technology greatly improves contains 60 per cent lead — a from the A*STAR Institute volatile alkali ions in solution
the material quality and toxic metal, which although once of Materials Research and and the stabilizing agent
performance of thin films commonly used in electronics, Engineering, in collaboration with suppressed volatilization,
of a lead-free ‘piezoelectric’ has been banned. National University of Singapore allowing the compositions
material1. This development by researchers, have shown that a of the resulting films to be
A*STAR researchers promises solution-based fabrication method well controlled.
to unlock a lead-free alternative ‘‘It has been using a painstakingly formulated “With the film composition
to the lead–zircon–titanate challenging cocktail of chemical agents can under control, we were
(PZT) standard. to achieve produce thin films of KNN with able to study the phase
Piezoelectrics are excellent a piezoelectric performance transitions in the material
remarkable materials that piezoelectric comparable to PZT. and their dependence on the
deform on application of an properties in “It has been challenging to chemical composition and stress
electric field and, conversely, KNN-based achieve excellent piezoelectric in the KNN-based thin films,”
produce an electric current thin films.’’ properties in KNN-based says Yao.
when compressed. They are thin films because the phase Through laser measurements
used in many electronics conditions needed for the combined with theoretical
© 2017 A*STAR Institute of Materials Research and Engineering
applications, including as An alternative material, piezoelectric effect depend very analysis from first-principles
electromechanical actuators which is based on a sensitively on composition,” simulations, the team confirmed
and as sensors for strain and potassium–sodium–niobate explains Yao. “In KNN, it has that the performance of their
acceleration. Thin films of composition and is known been difficult to suppress the loss piezoelectric films makes them
piezoelectric materials are as KNN, is being used as of volatile elements needed for a viable lead-free alternative
also being integrated into a replacement for PZT in these conditions.” to PZT.
microelectromechanical systems many bulk applications. Yet thin Yao and his team overcame
(MEMS) circuits and devices. films of KNN are problematic this problem by adding a 1. Wang, Y., Yao, K., Qin, X.,
Mirshekarloo, M. S., Liu, X., Tay, F. E. H.
For decades, PZT was because they are subject to a blend of chemical stabilizing High piezoelectric performance
the piezoelectric material of breakdown of composition agents — refined over more and phase transition in stressed
choice, since it offered the control and the atomic than ten years of research — to lead-free (1–x)(K,Na)(Sb, Nb)
O 3-x (Bi,Na,K)ZrO 3 thin films.
degree of deformation or ordering needed to produce the the precursor solution used to Advanced Electronic Materials 3,
sensitivity needed for practical piezoelectric effect. prepare the KNN thin films. 1700033 (2017).

INVISIBILITY IS
WITHIN SIGHT
PHOTONICS The theoretical discovery of transparent
particles that break the previously accepted
limit of visibility opens a new door in the
search for perfect transparency.
Transparent particles with light that hits them. It has long be suppressed in transparent transparent particles have
extraordinarily high refractive been accepted that all particles particles at wavelengths some degree of scattering. We
indices can become almost undergo Rayleigh scattering, longer than the particle scale have been able to reveal a new
invisible at wavelengths longer and that the minimum amount if their refractive index is phenomenon that could be
than the particle size, an of scattering occurs when the extraordinarily high. used to design ultra-transparent
A*STAR-led theoretical study refractive index — a measure optical materials.”
has shown1. The discovery of the ‘slowness’ of light passing Rayleigh scattering occurs
challenges the accepted wisdom through a medium compared ‘‘This phenomenon when light is absorbed by
around the limits of light with a vacuum — is less than two. could be used a molecule — producing a
scattering and visibility, and Water, air and glass all meet this to design ultra- separation of positive and
could lead to a new class of condition, suggesting that the transparent negative charges known as an
‘invisible’ materials. Rayleigh scattering that makes optical materials.’’ electric dipole — and re-emitted
The scattering of sunlight the sky blue is the least visible by the dipole at the same energy.
from gas molecules in the state physically achievable. This can occur at all wavelengths,
atmosphere is what makes Boris Luk’yanchuk and “There have been many but is more efficient at short
the sky look blue, allowing us colleagues from the A*STAR attempts to reduce scattering,” wavelengths, which is why the sky
to effectively see what would Data Storage Institute, in says Luk’yanchuk. “For is more blue (short wavelength)
otherwise be a transparent collaboration with researchers example, suppression of the than red (long wavelength).
medium. This process, known from the Australian National back reflection of radar signals “In our theoretical study
as Rayleigh scattering, occurs University, have now upset this has been widely studied as part we found that for very high
when molecules or particles are status quo with the discovery of the development of stealth refractive index materials, the
smaller than the wavelength of that Rayleigh scattering can technology. Yet even very small contribution of the electric
dipole becomes vanishingly
small,” explains Luk’yanchuk.
“Specifically, we found that
Rayleigh scattering,
the electric dipole mode
responsible for the
blue hue of the sky, in small particles of such
can be suppressed materials is suppressed by the
in subwavelength emergence of another dipole
particles with
mode, resulting in ultra-weak
extraordinarily high
refractive indices. scattering below the Rayleigh
limit. The challenge now is to
find or develop materials with
a high enough refractive index
© Dave and Les Jacobs/Blend Images/Getty
at the wavelength of interest to

suppress Rayleigh scattering.”
1. Luk’yanchuk, B., Paniagua-

Domínguez, R., Kuznetsov, A. I.,
Miroshnichenko, A. E. &
Kivshar, Y. S. Suppression of scat-
tering for small dielectric particles:
anapole mode and invisibility.
Philosophical Transactions A 375,
20160069 (2017).

Gout has been

associated with
© xxxxxxxxxxxxxx
overindulgence
– sometimes
unfairly.

fluids which act as first line of

immune defense.
One way of mimicking
what happens in gout is to inject
IMMUNOLOGY MSU crystals into the peritoneal
cavity of mice; this usually
triggers an influx of immune
cells and inflammation. It also
raises levels of two complement
proteins, C3a and C5a, the
team found.
Experiments revealed
THE ROLE OF that incubating immune

cells in the presence of C5a,
CRYSTALS but not C3a, increased levels
IN THE ‘DISEASE of the cytokines, IL-1β and

IL-1α. “This is a hallmark of
OF KINGS’ inflammasome activation,” says
Hanif Khameneh, one of the
Gout is associated with unhealthy lead investigators.
living, but its underlying Next, the team used mice
engineered without receptors
mechanism has been a mystery.
for either complement protein.
Those lacking C5a receptors,
but not C3a receptors, failed to
An attack of gout is said to cytokines. These rally immune show the usual infiltration of
be like your joint catching cells, which release further immune cells, and inflammation
fire, and someone slamming substances, resulting in excessive in response to MSU crystals.
it with a hammer to put out inflammation and pain. Treating mice with a drug that
the flames. Now A*STAR blocks C5a receptors produced
researchers have identified how a similar result. C5a most
the build-up of monosodium ‘‘Complement likely triggers inflammasome
urate (MSU) crystals in the is involved activation by boosting cellular
joints triggers such excruciating in initiating levels of reactive oxygen species,
pain, raising the prospect of inflammation,” which are toxic at high levels.
new treatments. says Khameneh, The discovery could
Gout has been dubbed the “targeting it have consequences for gout
disease of kings, because it is may benefit gout treatment. Current drugs merely
sometimes — but crucially, not sufferers.’’ dampen pain and inflammation,
always — associated with the rather than addressing its
overconsumption of alcohol root cause. “At least in our
and fatty or protein-rich foods. Inflammasomes can become mouse model, we’ve shown
These boost levels of blood activated in response to bacterial that complement is involved
uric acid, which crystalizes in or viral invaders, but they also in initiating inflammation,”
the joints: but it was unclear respond to particulate structures says Khameneh. “Targeting
how these crystals caused such as MSU crystals. To complement may therefore
severe inflammation. investigate how MSU activates benefit gout sufferers.
One clue came with the inflammasomes, a team led
discovery of inflammasomes, by Alessandra Mortellaro 1. Khameneh, H. J., Ho, A. W. S., Laudisi,
© Johnrob/iStock/Getty
F., Derks, H., Mortellaro, A. et al. C5a

complexes of molecules of the A*STAR Singapore
© xxxxxxxxxxxxxx
Regulates IL-1β Production and

within cells that respond to Immunology Network turned
leukocyte recruitment in a murine
environmental “danger signals” to the complement system, a model of monosodium urate crys-
by mediating the release of group of more than 20 proteins tal-induced peritonitis. Frontiers in
active message molecules called circulating in blood and tissue Pharmacology 8, 10 (2017).

Altered gene
promoters in gastric
cancer cells (blue)
helps them evade
CANCER detection by cells of
the immune system
(green).
HOW STOMACH
TUMORS HIDE
Alterations in gene
regulation make gastric
cancer cells less visible to
the immune system.
Gastric cancer cells are helped Institute of Singapore, primary wrapped around — to locate the reversible nature of
to evade the immune system by author of the study. “More and identify active gene promoter activity can be
alterations in gene regulation, than half of the genes in the promoters. Comparing exploited to modulate the
according to new work by human body have more than active promoters in gastric immunogenicity of gastric
A*STAR researchers. This one promoter controlling cancer cells with those in cancer tumors and make them
mechanism might apply to them, and cancer cells often healthy gastric cells enabled more sensitive to immunotherapy.”
a wide range of cancers, and exploit this by using abnormal identification of almost 2,000 Furthermore, analysis of
could be exploited to improve promoters to drive malignancy. promoters that are altered in a cancer genetics database
cancer treatments. We wanted to identify which gastric cancer. revealed many similar
Gastric cancer is promoters are abnormally The alterations in promoter alterations in other
among the most common activated or silenced in gastric promoters not only conferred cancers — colon cancer,
and deadly forms of the cancer cells.” cancerous properties, but kidney renal clear cell
disease and has limited treatment also reduced the expression carcinoma and lung cancer
options. The impact of of proteins in tumor cells — suggesting that similar
gastric cancer means that its ‘‘Studying the that would enable the mechanisms apply to many
genetics have been studied tumor promoter immune system to detect cancers. The researchers
extensively. Patrick Tan, from the profiles of them. This mechanism helps now aim to determine the
A*STAR Biomedical Research the cells evade the immune cellular pathways involved
gastric cancer
Council, and an international system, but also reduces the in the function of the
research team, now provide new
patients can effectiveness of immunotherapy, altered promoters. “Targeting
insight by studying variation in
help to identify which exploits the these pathways can
gene promoters, components suitable immune system to attack potentially increase the
of DNA that regulate candidates for the tumor. Ultimately, the response rates of gastric cancer
gene expression. immunotherapy.’’ findings could be used to patients to immunotherapy,”

“Promoters act as improve treatment. says Qamra.
multifaceted switches that “Studying the tumor
1. Qamra, A., Xing, M., Padmanabhan, N.,
turn genes on or off, regulate The researchers used promoter profiles of
Kwok, J. J. T., Zhang, S. et
the amount of gene expression a technique called Nano- gastric cancer patients can al. Epigenomic promoter
and control a gene’s output,” ChIP-Seq that uses molecular help to identify suitable alterations amplify gene isoform
and immunogenic diversity in
explains Aditi Qamra tags on histones — proteins candidates for immunotherapy,” gastric adenocarcinoma.
from the A*STAR Genome that DNA molecules are explains Qamara. “Also, Cancer Discovery 7, 630–651 (2017).

sublime under the high vacuum quite a surprise, as the common

conditions required for imaging understanding is that sulfur
techniques, such as transmission is highly insulating, and it is
electron microscopy. difficult to directly lithiate
NANOMATERIALS With an initial aim of getting sulfur particles.”
a better look at sulfur during lith- As well as gaining
iation, Guangyuan Wesley Zheng fundamental insights into
from the A*STAR Institute of lithium’s interaction with
Materials Research and Engineer- sulfur, the team showed the
ing co-led an international effort MoS2-wrapped hollow sulfur
to seal sulfur nanoparticles inside nanoparticles could become
sheets of a 2D nanomaterial to more than just a study tool.
UNLEASHING suppress sublimation. The team

selected nanoflakes of molybde-
Sealing the sulfur within MoS2
restricted the damaging volume
SULFUR’S POTENTIAL num disulfide (MoS2), a material change and the loss of lithiated
known to have a good binding in- sulfur into the electrolyte,
Sealed sulfur particles show teraction with sulfur and lithium avoiding the two key hurdles
promise for renewable energy sulfide, to encase the particles. blocking the use of sulfur in
lithium-ion batteries.
storage technology.
“I do believe there is
‘‘We are currently practical application for the
working with a technique in batteries, if we
Hollow sulfur nanospheres Sulfur does have drawbacks, battery company can further improve the MoS2
wrapped inside sheets of molybde- however. Once ‘lithiated’, it to develop a production process,” Zheng says.
num disulfide could form the ideal becomes soluble in the battery’s commercial “We are currently exploring
cathode material for the next gen- electrolyte, and so can break the scaled-up production
prototype.’’
eration of lithium-ion batteries, away from the cathode. Sulfur of the encapsulated sulfur
research from A*STAR suggests1. also swells by up to 80 per particles, and working with a
The amount of energy a cent when soaking up lithium. The researchers were battery company to develop a
lithium-ion battery can hold is Both processes shorten the then able to examine the commercial prototype battery,”
partly determined by the amount cathode’s life. nanoparticles using transmission he says.
of lithium ions its cathode can Complicating matters, electron microscopy. “The most
1. Tang, W., Chen, Z., Tian, B., Lee, H.-W.,
absorb. Sulfur’s high chemical the process by which sulfur significant insight we gained
Zhao , X., et al. In situ observation
affinity for lithium ions means a absorbs lithium is hard to related to the ‘lithiation kinetics’ and electrochemical study of
lithium-sulfur battery could hold study in situ. Sulfur has a of sulfur particles,” Zheng says. encapsulated sulfur nanoparticles
by MoS 2 flakes. Journal of the
five times the energy of today’s high vapor pressure, which “We observed relatively fast American Chemical Society 139,
lithium-ion batteries. means that its atoms rapidly lithium reaction kinetics — 10133−10141 (2017).
Reprinted with permission from Ref 1. Copyright 2017 American Chemical Society
1 μm 100 nm
Scanning electron microscopy image showing a sheet of the MoS2-wrapped sulfur nanoparticles.

GENETIC
DISEASE
MUTATION
DISCOVERED FOR
JOINT DISORDER
A rare genetic mutation
associated with a
developmental disorder
could be a treatment A nerve cell, with a
target for related protective myelin
sheath indicated
conditions in adults. in yellow.
The discovery of a rare genetic resulted in several fetuses dying for a molecule called LGI4. This in the early stages of pregnancy,
mutation associated with a dev- before birth or soon after. molecule is secreted by Schwann and people with a family history
astating developmental disorder “We knew that it was cells, which produce the fatty of the disease could be offered
called arthrogryposis multiplex probably going to be genetic sheath called myelin that covers genetic counseling before
congenita could also provide because many of these families and insulates nerve cells, and pregnancy. It also opens the
researchers with a new treatment had multiple individuals with enables them to conduct electrical door to research that could help
target for a group of related neu- this condition,” says Shifeng Xue impulses quickly and effectively. adults with degenerative diseases
rodegenerative diseases, including from the A*STAR Institute of It suggests that LGI4 plays a key such as multiple sclerosis, where
multiple sclerosis, in adults. Molecular and Cell Biology. role in the myelination process. the immune system attacks and
Arthrogryposis multiplex LGI4 and Schwann cells destroys myelin.
congenita is a common birth operate in the peripheral nervous “We’re hoping that by
defect, affecting around 1 in ‘‘We’re hoping system — the parts that don’t identifying LGI4 as being
3,000 live births. Babies with we can develop include the brain and spinal cord important for Schwann cell
the disorder have stiff joints and LGI4 as a — which controls movement and development, differentiation and
their limbs become locked into therapeutic sensory function. myelination, we can possibly
awkward positions because of a biologic to This new mutation develop it as a therapeutic
© ROGER HARRIS/SCIENCE PHOTO LIBRARY/Getty
lack of movement in the womb. stimulate stopped the LGI4 gene from biologic to stimulate myelination,”
The disorder can be caused by myelination.’’ functioning altogether, so those says Bruno Reversade, research
crowding in utero — for example affected by it didn’t have any director at the A*STAR Institute
with twin pregnancies — but it myelin on their peripheral of Medical Biology.
also occurs when genetic muta- But when the researchers nerve cells. This caused severe
tions affect the normal develop- looked at the families’ genomes, malformation of their limbs and 1. Xue, S., Maluenda, J., Marguet, F.,
Shboul, M., Quevarec, L. et al. Loss-
ment of muscles and nerves. they couldn’t find any of the also affected the muscles of the of-function mutations in lgi4, a
A study led by researchers known mutations associated diaphragm so their lungs didn’t secreted ligand involved in Schwann
from A*STAR looked at a group with arthrogryposis. develop properly. cell myelination, are responsible for
arthrogryposis multiplex congenital.
of families affected by a severe Instead they discovered a The discovery means the The American Journal of Human
form of arthrogryposis that new mutation in the gene coding mutation could be screened for Genetics 100, 659–665 (2017).

yields considerable variability

in the cells, which can make it
PANCREATIC STEM difficult to interpret the results of
DIABETES
CELLS ON TAP different studies. It also involves
many time-consuming steps.
Growing pancreatic stem cells Researchers at the A*STAR
Institute of Medical Biology
will help research on diabetes. and the Genome Institute of
Singapore have developed a new
method that reduces the number
of steps and ensures a more
A new cell culture procedure glucose from the blood by the cells to explore what goes wrong consistent supply of beta cells, by
developed by A*STAR will body’s cells. Diabetes therefore in beta cells and to develop generating pancreatic stem cells
assist the study of diabetes and results in high blood glucose new ways to control or correct and expanding them.
facilitate better treatments1. “Our levels, which can be fatal if the problems. It has proved “We found a way to propa-
discovery will enable studies not controlled. The levels are difficult and time-consuming, gate pancreatic stem cells, which
of how the pancreas forms and controlled by administering however, to generate suitable are developmentally much closer
why certain cells malfunction in synthetic insulin, but if too much cell lines. Pluripotent stem to the beta cells we need,” says
diabetes,” says Jamie Trott from is given, there is a risk of low cells — those able to develop Trott. The researchers explored
the A*STAR team. blood glucose. These and other into a wide range of mature modifications to the cell culture
Type 1 diabetes occurs risks of diabetes can lead to long- cell types — can be guided conditions in which these stem
when insufficient insulin is term complications, including through stages that mimic cells developed, eventually dis-
released into the bloodstream problems with vision and the embryonic development, leading covering a cocktail of signals that
by the beta cells of the pancreas. circulatory system. to the formation of beta cells. enabled the cells to grow.
Insulin promotes the uptake of Researchers use cultured Unfortunately, this procedure “Seemingly minor differences
in culture conditions turned
out to be the difference between
success and failure,” says Trott.
“It took a while to identify the
importance of these variables
and to control their effects.”
A key feature of the new
procedure is that the pancreatic
stem cells are self-renewing, so
they can be expanded repeatedly
to generate an enormous supply
of beta-like cells, without the
frequent need to go through
the many stages of embryonic
development. This should make
it easier, faster and cheaper to
produce supplies of beta cells for
scientists investigating diabetes.
The researchers plan to
improve their technique and
investigate the molecular

factors controlling the
cells’ development.
1. Trott, J., Tan, E. K., Ong, S., Titmarsh,

Pancreatic stem
D. M., Denil, S. L. I. J. et al. Long-term
cells that could
culture of self-renewing pancreatic
aid diabetes
progenitors derived from human
research.
pluripotent stem cells. Stem Cell
Reports 8, 1675–1688 (2017).

An immobile mutant zebrafish developing fish embryos were

first described by scientists more without fast-twitch muscle fibers,
than 20 years ago turns out to bundles of long and slender cells
have defects in the same gene that are needed for bursts of
GENETICS as people with a rare muscle- rapid movement.
degenerating disorder called They named the mutated
nemaline myopathy, an A*STAR gene frozen. However, they had
study has found. no idea where the gene was in
The study points to a central the zebrafish genome or what
role of the faulty gene, known kind of protein it encoded.
as myo18b, in the assembly of Ingham and his team have
sarcomeres, the force-generating now filled in those missing
FISHING FOR component of the muscle cell.

It also helps explain the poor
details. They used a series of
genetic markers and fish breeding
A DISEASE GENE motor function seen in patients experiments to narrow down the
who have mutations in this gene location of frozen to a relatively
Mutant zebrafish help explain — an insight that mouse models short stretch of around 1.4 million
the cause of a rare muscle- could not provide, because DNA letters long on chromosome
mouse embryos that lack myo18b 10. The researchers then compared
degenerating disorder.
die before their skeletal muscle this small region with matching
has developed. DNA from other fish species,
including tilapia and pufferfish.
They found that what had
‘‘The zebrafish been called frozen is actually
mutant provides the zebrafish version of a
the only animal known gene, myo18b, which
model for encodes a poorly characterized
studying the member of the myosin motor
effects of the protein family. In the zebrafish,
myo18b mutation the protein-coding portion of
on skeletal the myo18b gene was about
50 per cent identical to its
muscle.’’
human counterpart, which
has been linked to rare genetic
As Philip Ingham, head muscle disorders.
of the Developmental and Detailed analyses of these
Biomedical Genetics Laboratory myo18b-deficient fish provide
at the A*STAR Institute of the first definitive evidence that
Molecular and Cell Biology, this motor protein is needed
points out: “The zebrafish for proper skeletal muscle
mutant provides the only animal development. Ingham says the
model for studying the effects fish can now serve “as a model
of the myo18b mutation on for better understanding the role
© 2017 A*STAR Institute of Molecular and Cell Biology
skeletal muscle.” of MYO18B in the assembly of

Ingham worked with the sarcomere,” and he hopes
postdoctoral fellows in Singapore they can help scientists find
and England to characterize ways to treat myopathy disorders
a particular strain of mutant in people.
zebrafish first identified by
German researchers in 1996. 1. Gurung, R., Ono, Y., Baxendale, S.,
Lee, S. L., Moore, S. et al. A zebrafish
At the time, the scientists were
model for a human myopathy asso-
looking for gene mutations that ciated with mutation of the uncon-
Fast-twitch skeletal muscle from normal zebrafish larvae (top) shows the characteristic
striated pattern formed by the long chains of sarcomeres within each fiber, whereas affect zebrafish motility, and ventional myosin MYO18B. Genetics
muscle from frozen mutant larvae of the same age (bottom) lacks any striation. they found one that meant the 205, 725–735 (2017).

BRAIN
FUNCTION
FINE-TUNING
EXCITATION
FOR SURVIVAL The fly central
nervous system
A small molecule plays a big showing a subset
of glia in blue. Mir-
role in protecting the nervous 263a protects
these cells from
system’s support cells from neurodegeneration.
excessive stimulation.
Glutamate is the primary in glia, mir-263a, protects flies They found that mir-263a Previous studies have shown
excitatory neurotransmitter from developing a movement depletion triggers glial cell that glia express all the major
of the central nervous system. defect associated with death and that restoring mir- types of glutamate receptors
In excess it causes cells to neurodegeneration. 263a expression in a subset and that they contribute to
become overexcited, which of glia not only promotes cell maintain neuronal function by
contributes to neuron death ‘‘A single survival, but remedies the flies’ clearing extracellular glutamate,
in neurodegenerative disease. impaired climbing. but little is known about the
microRNA
Now, a study of flies led by Mir-263a is a small effects of glutamate on glia
can target a
Sherry Aw, at the A*STAR non-coding RNA molecule themselves. This study shows that
Institute of Molecular and
family of genes (microRNA) that suppresses glia, like neurons, are susceptible
Cell Biology, highlights the with a similar the expression of multiple to glutamate overstimulation, and
importance of also curbing molecular target genes. In the brain of highlights a key role for mir-
glutamate stimulation in glia. function.’’ mir-263a mutant flies, the 263a in fine-tuning the levels of
Glia are generally considered authors detected an increase glutamate receptor expression in
the nervous system’s support Flies lacking the gene in the expression of over glia and thus, their sensitivity to
cells, although important encoding mir-263a were unable 70 genes, including several the neurotransmitter.
contributions to brain to climb up the walls of a encoding for glutamate It will be interesting to
signaling have also recently cylindrical vial when flipped receptors. When the authors determine whether a similar
© 2017 A*STAR Institute of Molecular and Cell Biology
been described. from a horizontal to vertical reduced the expression levels mechanism contributes to
Although glia account position. The climbing defect of these receptors in glia of neurodegenerative diseases
for 90 per cent of the cells in worsened with age, reflecting a flies lacking mir-263a, glia cell in humans and to explore the
the human brain, research on progressive decline in nervous numbers were restored and exciting possibility of developing
the molecular mechanisms system function. The authors the movement defects were microRNA-based therapeutics to
of neurodegenerative disease were surprised when they suppressed. “MicroRNAs can treat them, says Aw.
mainly focus on neurons. In examined the expression pattern be an efficient mode of gene
their article in Cell Reports, of mir-263a as they found that it regulation as a single microRNA 1. Aw, S. S., Lim, I. K. H., Tang, M. X. M.
& Cohen, S. M. A glio-protective role
Aw and colleagues show that is predominantly expressed and can target a family of genes with of mir-263a by tuning sensitivity
a small RNA that regulates functional in glia, rather than a similar molecular function” to glutamate. Cell Reports 19,
glutamate receptor expression in neurons. explains Aw. 1783-1793 (2017).

Everyone who has ever had side-effects. With the number

to endure eczema knows just of cases increasing, scientists
how irritating the symptoms are searching for what causes
are. Now A*STAR researchers the condition.
IMMUNOLOGY have pinpointed a genetic Now, Olaf Rotzschke and his
predisposition to the condition, team at the A*STAR Singapore
opening possibilities for Immunology Network have
new treatments. uncovered a common genetic
The itchy, red and mutation which increases the risk
cracked skin typical of atopic of atopic dermatitis. As part of a
dermatitis, otherwise known large study aimed at identifying
as eczema, is an inflammatory drug targets for allergies and
NEW HOPE FOR condition which affects up

to one in five children, many
other immune conditions,
Rotzschke’s team collected blood
ECZEMA SUFFERERS of whom continue to suffer samples and clinical data from
into adulthood. 600 Singaporean residents.
Scientists have scratched the Topical corticosteroid The scientists analyzed
surface of the genetics behind creams and other medication the activity of more than
can treat persistent symptoms 30,000 genes in each of the
an irritating skin condition.
and severe cases, but can induce blood samples and compared
A*STAR scientists have

discovered a genetic
predisposition for
eczema which reduces
levels of the molecule
SIRL-1 present on
immune cells called
monocytes (pictured).
‘‘Lorem ipsum
dolor sit amet,
consectetur
adipiscing elit.
Lorem ipsum
dolor sit amet,
consectetur
adipiscing elit.’’
© Westend61/Getty

this to 5 million common The properties of surfactants, surfactants, those with more
genetic mutations, referred substances that lower the compact heads and longer tails
to as single nucleotide surface tension of a liquid, can remained in a flat layer, while
polymorphisms (SNPs), for be fine-tuned by tweaking their those with bulkier heads and
each individual. CHEMISTRY molecular structure, according shorter tails began to buckle into
After analyzing this to a recent A*STAR study1. This undulating waves. In general,
extensive database, the method could help researchers the behavior of the surfactant
researchers discovered that the develop better surfactants also depended on the position of
activity of the gene VSTM1, for a variety of applications, chemical groups around its head.
which encodes a protein called from aiding drug delivery, or
SIRL-1, was heavily dependent improving the efficiency of
on a specific SNP. This oil drilling, to boosting the ‘‘Our simulations
mutation, analysis revealed,
lowered SIRL-1 levels on a
SIMULATING cleansing ability of soap.
Surfactants are molecules
provide a guideline
on choosing the
subset of immune cells called SURFACTANTS with split personalities. They types of surfactants
monocytes and increased the typically have a hydrophilic depending on
risk of atopic dermatitis by 30 Small changes to a ‘head’ that attracts water, and a
the specific
per cent. surfactant’s structure hydrophobic ‘tail’ that prefers
applications.’’
SIRL-1 is a molecule oily molecules. Surfactants can
influence its ability
found on the surface of surround tiny oily droplets
monocytes, and other immune to encapsulate oily to form a structure called a The researchers then
cells, and functions to regulate molecules. micelle, which allows the oily continued to increase the
the defense against invading molecules to be dispersed and concentrations of surfactants in
pathogens. It is not currently stable in water. the intermediate layer. Those with
known which molecule, or Freda Lim and colleagues at more compact heads and longer
ligand, naturally docks to the A*STAR Institute of High tails formed bud-like structures
SIRL-1 inside the human Performance Computing have filled with decane, but did not
body, but identifying such a now shown that rearranging the release free micelles. In contrast,
molecule could result in new atoms in a common surfactant those with the bulkier heads and
intervention strategies for can have a big impact on its shorter tails formed buds that
eczema, Rotzschke explains. ability to form micelles. eventually broke free from the
Reprinted with permission from Ref 1. Copyright (2017) American Chemical Society.
“Our Dutch colleagues The team performed surfactant layer (see image).
are very active in the hunt of computer simulations of a “The selection of surfactants
the ligand,” he says. “Topical family of six different alkyl depends on the purpose for
application of this compound benzenesulfonate molecules, which it is used, so there is
through a cream or ointment surfactants that, due to really no ‘best’ surfactant,”
could help suppress rashes their cost-effectiveness and explains Lim. “Our simulations
and other symptoms.” biodegradability, are widely used provide a guideline on choosing
His own team is casting in the detergents and petroleum the types of surfactants
a wider net, investigating industries. These molecules depending on the specific
the genetic profile of VSTM1 sport alkyl ‘tails’ containing applications.” The team now
and how this gene could be 12, 14 or 16 carbon atoms, and plans to study how different
involved in other conditions. some have short alkyl groups stimuli trigger the rupture of the
“We have already looked in in various positions on their surfactant micelle structures,
a subset of potential diseases benzenesulfonate ‘heads’. and how the substances trapped
but the search is by no means The researchers first within these structures can be
exhausted,” he says. simulated how the surfactants released for applications.
behaved in a single-molecule
1. Kumar, D., Puan, K. J., layer, trapped between 1. Tan, J. S. J., Zhang, L., Lim, F. C. H. &
Andiappan, A. K., Lee, B., Cheong, D. W. Interfacial properties
Westerlaken, G. H. A., et al. A surfactant (shown in red, yellow and water and a colorless, oily and monolayer collapse of alkyl
A functional SNP associated turquoise) with a 14-carbon ‘tail’ forms hydrocarbon called decane. As benzenesulfonate surfactant
with atopic dermatitis controls an undulating layer between water monolayers at the decane-water
the concentration of surfactant
cell type-specific methylation (colorless) and decane (green), which interface from molecular dynamics
of the VSTM1 gene locus. develops into buds (middle) and then molecules increased to the point simulations. Langmuir 33,
Genome Medicine 9, 18 (2017). free micelles (lower). where the layer was packed with 4461−4476 (2017).

IMMUNOLOGY
NEW STRATEGY
FOR FIGHTING Lund University
and A*STAR
INVADERS researchers reveal

that fragments
of the blood
A surprise finding shows clotting enzyme
thrombin (shown)
in skin wounds fragments protect the body
of a blood clotting enzyme against infections
by aggregating
collect and consume bacteria.
bacteria and their toxins.
A previously unknown Using an array of infection,” says Petrlova. “We wounds is of evolutionary
mechanism used by the body to techniques, including believe this to be a fundamental significance to our survival.
prevent wound infections has been biophysical, biochemical, and mechanism for taking care of Compared to antibiotics,
discovered by team of researchers microbiological methods, both bacteria and their toxins innate immunity has been
from A*STAR, Lund University, fluorescence and electron during wound healing.” around for millions of years,
Nanyang Technological University, microscopy, and computer and we should consider the
and Copenhagen University1. modeling, the team found that application of these concepts
This finding could provide an enzyme secreted by immune ‘‘Compared in an era of increasing
scientists with a new way to fight cells such as neutrophils and to antibiotics, antibiotic resistance.”
infection, a critical development macrophages cuts up thrombin, innate immunity The team’s finding could
when many microbes are an enzyme that plays an has been around also have implications for dis-
becoming increasingly resistant important role in blood clotting, for millions of eases such as Alzheimer’s and
to antibiotics. into fragments. These thrombin years, and we Parkinson’s. “Various aggregat-
Skin wounds are open fragments then collect bacteria should consider ing proteins can cause amyloid
doors for bacteria to enter the and their toxins together. This the application diseases in the skin or internal
body and cause infections. The occurs rapidly in a wound, of these organs such as the brain,” says
body uses a range of different and the invaders are gobbled concepts in an Petrlova. “Such degenerative
strategies to protect itself up by inflammatory cells. This era of increasing diseases could be caused by
against this threat, including phenomenon was not seen in antibiotic over-activation of a mechanism
resistance.’’
© MOLEKUUL/SCIENCE PHOTO LIBRARY
blood clotting and immune normal blood plasma; it was that is supposed to protect us
responses. In a surprising find, observed only in wounds. from infections.”
Jitka Petrlova at Lund University, The discovery suggests a new
Sweden, together with Peter approach for fighting bacteria. Petrlova says: “Nature has 1. Petrlova, J., Hansen, F. C., van der
Plas, M. J. A., Huber, R. G., Mörgelin,
Bond’s team at the A*STAR “Perhaps, we don’t need to kill effectively created different M. et al. Aggregation of throm-
Bioinformatics Institute, have bacteria with antibiotics. Instead, defense mechanisms, and bin-derived C-terminal fragments
discovered a strategy that we could simply gather them wound healing provides a rich as a previously undisclosed host
defense mechanism. Proceedings of
the body uses to neutralize together and give the body a source of new discoveries. the National Academy of Sciences
invading microbes. helping hand in combating The ability to effectively heal USA 114, E4213–E4222 (2017).

have the added benefit of being Constrained groove pressing

more dent resistant and more involves repeated pressing of a
machinable, and better able to thin sheet of metal, such as the
shield electromagnetic radiation magnesium alloy, between heat-
MATERIALS and dampen vibrations, than ed, finely corrugated dies. This
aluminum alloys. stretches — or strains — the ma-
The trade-off with magnesium terial over very narrow domains,
is that it is notoriously difficult causing plastic deformation
to work with, requires high while preventing damage and
temperatures for formability and inducing the microscopic crystal
has generally lower strength. grains to recrystallize into a finer
Finding a way to improve the microstructure. By turning the
BETTER PROPERTIES mechanical properties and

workability of magnesium alloys
sheet by 90 degrees between each
pressing step, the material is re-
FOR A MAGNESIUM could open many new applications peatedly strained until the entire
ALLOY for the material with real-world

benefits like improved fuel
sheet has been processed.
Optimized processing improves the economy in aircraft, watercraft

and land vehicles, and lighter ‘‘This processing
mechanical strength and workability mobile phones. led to improved
of magnesium alloy as a lighter Kai Soon Fong and colleagues mechanical
alternative to aluminum alloy. from the Singapore Institute of strength and
Manufacturing Technology and ductility, making
Nanyang Technological Univer- it tougher
sity have now devised a pre-pro- and easier to
Magnesium alloy can be made the go-to light metal for many cessing method that significantly shape at room
stronger and more workable by structural applications, from improves the mechanical strength temperature.’’
hot pressing under optimized aircraft fuselages to smartphone and ductility of AZ31, the most
conditions to produce an bodies. It is light, corrosion- widely used magnesium alloy.
ultra-fine crystalline structure, resistant and is relatively easy “We have shown that the The material is then heated,
A*STAR researchers have to shape, weld and work. Alloys properties of commercial AZ31 or annealed, to remove residual
shown1. The improved material of magnesium are up to one- magnesium sheet can be enhanced stress, but at a faster heating
means magnesium alloy will third lighter than alloys of by severe plastic deformation rate and shorter time than
have broader applications as an aluminum, and are particularly using an orthogonal constrained usual, to prevent the grains from
ultra-light structural material. promising for applications groove pressing technique with enlarging again.
Aluminum alloy is currently where weight is critical: they fast post-annealing,” says Fong. “By optimizing the pro-
cessing temperature and strain
rate, we were able to achieve an
ultrafine-grained microstruc-
ture, which does not physically
Reprinted from Ref. 1, Copyright (2017), with permission from Elsevier.
change the alloy, but improves its

mechanical properties through
grain refinement,” says Fong.
“This processing led to improved
mechanical strength and ductil-
ity, making it tougher and easier
to shape at room temperature.”
1. Fong, K.S., Danno, A., Tan, M.J., &

Chua, B.W. Tensile flow behavior of
AZ31 magnesium alloy processed
by severe plastic deformation and
100μm 20μm post-annealing at moderately high
temperatures. Journal of Materials
Orthogonal groove strain pressing and fast annealing dramatically shrinks the grain size of AZ31 magnesium alloy, resulting in increased Processing Technology 246,
strength and room temperature ductility. Before processing (left), after processing (right). 235–244 (2017).

energies at the bacterium

Bacillus pumilus, a spore-
forming bacterium common
in soil.
STERILIZATION The first results threw
up a troubling surprise.
“When we looked at the
data we couldn’t understand
why we ended up with more
bacteria than we started with,”
says Yong. The researchers
assumed there must have
BETTER WAYS been some error in the

experiment, but when they
WITH X-RAYS repeated the process, the same
thing happened.
Low-energy X-rays are “This got us excited,”
surprisingly effective at killing adds Yong.
Further investigation
bacterial spores, offering revealed that short
improved sterilization techniques. duration exposure was ‘waking
up’ the spores rather than
killing them. But then came
a second and much more
Low-energy X-rays are manufacturers, who seek useful surprise. In runs of
able to sterilize materials, improved sterilization processes longer duration the lower
offering a potentially cheap and during the production and use energy X-rays were more
effective alternative to current of medical equipment and in the effective at killing the spores
techniques, A*STAR researchers food industry. than higher energy rays. This
have shown. was the crucial breakthrough
The effect of the X-rays that allows the new, safer
on bacteria when they are ‘‘If the exposure and more convenient
in a spore state, a dormant is long enough sterilization system.
condition in which they are able we can kill all More work is needed
to survive harsh conditions, of the spores, to learn how to keep the
was examined by Derrick Yong including X-ray energies as low as
and colleagues at the Singapore those that we possible, while adjusting the
Institute of Manufacturing unintentionally length of exposure to ensure
Technology, in collaboration that all bacterial spores and
wake up.’’
with researchers from other free-living bacteria are killed.
Singapore universities. Yong reports that they have
They showed that “We typically picture already run trials of the system
surprisingly low doses of X-rays sterilization as involving on dried food products and
can kill spores: but that the extreme conditions such small medical devices. “We are
X-rays can also activate spores1. as high temperatures, toxic also working on new ways to
Fine-tuning the procedure is chemicals or deadly radiation generate the X-rays and methods
© Shannon Fagan/DigitalVision/Getty
key. “If the exposure is long sources,” says Yong. An to accelerate and scale up the
enough we can kill all of the alternative, the research whole process,” he adds.
spores, including those that suggests, is that a small and
we unintentionally wake up,” low-hazard tabletop X-ray 1. Ha, T. M. H., Yong, D., Lee, E. M. Y.,
© xxxxxxxxxxxxxx
Kumar, P., Lee, Y. K. & Zhou, W.

says Yong. source could do the job more
Activation and inactivation of
Yong explains that the conveniently and at lower cost. Bacillus pumilus spores
investigations were prompted The researchers began by by kiloelectron volt X-ray irradiation.
by conversations with local firing X-ray beams of different PLoS ONE 12, e0177571 (2017).

This new technique

may offer an
alternative to the
sterilization process-
es needed during
the production
and use of medical
equipment, and in
the food industry.
© xxxxxxxxxxxxxx

rely on a mechanism in phases are defined by specific

quantum physics by which patterns of electrons ‘dancing’
an object can simultaneously around each other.”
exist in a fuzzy superposition Different ‘dancing
QUANTUM of multiple states. This patterns’ produce different
MATERIALS
and other complementary two-dimensional states, or
quantum processes could ‘topological order’, in the
theoretically be utilized to same manner that pin pricks
perform complex operations in a piece of paper produce
many times faster than in different patterns. And
classical computers. Yet while quantum mechanical
despite significant research properties are generally very
A GUIDEBOOK and investment, quantum

computers are still undeveloped,
fragile, those manifested through
topological order are very
FOR EXOTIC STATES with only a handful of robust and could theoretically
rudimentary computing be utilized for practical
A theoretical model will platforms demonstrated applications such as topological
allow systematic study of experimentally. One of the quantum computers.
principal reasons for the lack of
a promising class of
progress is the fragility of the
peculiar quantum states. quantum states that support
‘‘Unlike
mechanisms like superposition. conventional
Electrons and light, phases of
Research on the fragile states of theoretical tools developed by the typical ‘information matter such as
matter that could give traction to A*STAR researchers1. carriers’ of quantum computing liquids or solids,
the many promises of quantum Long theorized but systems, both have quantum these phases
computing has been given a notoriously difficult to achieve properties that could be are defined by
boost by a comprehensive set of in practice, quantum computers exploited, but the trick is to specific patterns
create a physical material system of electrons
V1,2
that provides the interactions ‘dancing’ around
needed to make the quantum
each other.’’
phenomena appear. This takes
researchers into uncharted
physics territory. By analyzing the algebraic
Bo Yang and Ching structures of various simple
Figure adapted with permission from Ref. 1. Copyrighted by the American Physical Society.
Hua Lee from the A*STAR models and validating their
Institute of High Performance results against large-scale
Computing, in collaboration numerical computations, Yang
0.2 with researchers from China and and his team developed a model
the UK, have now developed a that allows physicists to study
general theoretical framework these topological states over
0 for a promising class of a wide range of conditions,
quantum material systems including states that are common
that will provide a universal in real materials.
-0.2 language for researchers in this “Our work can help both
pioneering field. theorists and experimentalists
“Our framework describes to understand and realize
a class of exotic phases of highly interesting new phases of
matter consisting of a very thin matter,” says Yang.
-4 -2 0 2 4 sheet of electrons subject to a
qx strong perpendicular magnetic 1. Yang, B., Hu, Z. X., Lee, C. H., Papić, Z.
Generalized pseudopotentials for
field,” explains Yang. “Unlike
A universal theoretical framework will help guide research on exotic topological states, the anisotropic fractional quantum
shown here in terms of the spatial distribution of electron states, which could be used to conventional phases of matter Hall effect. Physical Review Letters
realize practical quantum computers. such as liquids or solids, these 118, 146403 (2017).

HOW A COMMON
CANCER HIJACKS A
CANCER BIOLOGY WOUND-HEALING SWITCH
Understanding how head and neck squamous
cell carcinomas takes over wound-healing
processes could yield new treatments.
A*STAR researchers have 2013, Prabha Sampath’s group tongue cells from healthy of the defective switch. They
identified the molecular means by at the A*STAR Institute of patients, but absent from those revealed the precise molecular
which a common form of cancer Medical Biology discovered a from HNSCC patients. Their mechanism involved.
hijacks wound-healing processes molecular switch that triggers finding of elevated FSTL1 Sampath’s group further
to help it spread. The team hope the production of a microRNA expression in HNSCC samples showed that blocking FSTL1 and
their findings could lead to more called miR-198 in healthy skin, suggested the molecular switch DIAPH1 individually not only
effective treatments. and, upon injury, of the protein was indeed defective. In the thwarts the ability of HNSCC
Head and neck squamous cell follistatin-like 1 (FSTL-1). absence of miR-198, they also cancer cells to migrate, but also
carcinoma (HNSCC) is the sixth Given that uncontrolled found increased expression limits the spread of metastatic
most frequently-occurring cancer cell growth and migration of Diaphanous-1 (DIAPH1), tumors in immunodeficient
worldwide. It is caused by the are hallmarks of cancer and a another protein elevated mice. Notably, knocking out both
uncontrolled growth of squamous primary cause for metastasis, following skin wounding. genes simultaneously prevented
cells — thin, flat, scale-like cells Sampath’s team set out to test Using biochemical and formation of metastatic tumor
— in the outer layer of skin called their hypothesis that a defective cell culture experiments, the nodules. Analysis of The Cancer
the epidermis. wound-healing switch could researchers went on to show Genome Atlas (TCGA) data
Upon injury, epidermal cells facilitate HNSCC. that a protein that triggers cell base showed the survival of
called keratinocytes proliferate They used a technique called growth and differentiation HNSCC patients who expressed
and migrate toward wounds, fluorescent in situ hybridization called epithelial growth factor elevated levels of both FSTL1 and
a process that normally stops to show that miR-198 was (EGF), which is often elevated DIAPH1 was significantly shorter
when healing is complete. In expressed in abundance in in HNSCC, acts as a regulator than those who expressed them at
lower levels.
Further investigation
revealed FSTL1 and DIAPH1
promote HNSCC metastasis by
blocking the actions of other
proteins that normally prevent
cell migration.
The findings provide
new targets for therapeutic
intervention. “Additionally, we
are trying to identify biochemical
modulators of this defective
molecular switch which could
serve as novel and alternative

drugs to effectively treat this
deadly disease,” says Sampath.
1. Sundaram, G. M., Ismail, H. M.,

Bashir, M., Muhuri, M., Sampath, P.,
et al. EGF hijacks miR-198/FSTL1
wound-healing switch and steers
a two-pronged pathway toward
metastasis. Journal of Experimental
Elevated expression of DIAPH1 protein (shown in red) in a squamous cell carcinoma patient. Medicine 214, 2889–2900 (2017).

Scientists from A*STAR The shell utilizes

have developed a system eight alternating layers of
to transport a functional bovine serum albumin and
protein to the tissues of tannic acid grouped into
MICROCAPSULES the digestive tract where it four ‘bilayers,’ which, aside
may confer a range of health from offering protection,
benefits. This overcomes are also safe and cheap.
previous obstacles where Tannic acid also has its own
the molecules broke down antioxidant properties.
before they could reach their
target receptors.
Lactoferrin, found ‘‘We’re in
discussions
GETTING A naturally in breastmilk, is a
biologically active protein with several
FUNCTIONAL that provides vital support companies with
PROTEIN during early infancy. It
also has antimicrobial,
regard to how
we can move
FROM A TO B anti-inflammatory and our technology
cancer-fighting properties, forward.’’
A milk protein contained and can even help with
in gastro-resistant weight loss. Adults, however,
cannot benefit from dietary Kiryukhin’s team
microcapsules could be used
lactoferrin because the then performed both in
to give foods cancer-fighting, digestive enzymes and acid vitro and in vivo studies,
immune-boosting properties. in their mature stomachs first using simulated digestive
degrade the protein before it enzymes to verify the
can reach the small intestine. capsules’ desired properties,
It’s there, says A*STAR’s before testing them in mice. In
Maxim Kiryukhin, that their mouse model, the scientists
Reproduced from Ref. 1 and licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/) © 2017 E. Kilic et al.
lactoferrin’s receptors are fluorescently labeled the
thought to absorb the protein protein so they could track
and transport it to the lymphatic it through the stages of
system, where it provides its digestion, finding high
beneficial effects. levels of lactoferrin in the small
Kiryukhin, from the intestine and liver. Lactoferrin’s
Institute of Materials Research presence in the liver verifies
and Engineering and his team the protein’s ability to survive
have succeeded in protecting gastric digestion and be
lactoferrin molecules on their absorbed into the tissues of
journey through the stomach the intestine.
by coating them in layers of Kiryukhin says that
gastric-resistant casing. “We his team is now assessing
start with calcium carbonate whether their process is
microparticles. These are commercially viable: “We’re
porous and absorb lactoferrin to in discussions with several
produce a ‘core’ around which companies with regard
we can build our protective to how we can move our
shell,” says Kiryukhin. “Then, we technology forward.”
dissolve the calcium carbonate,
leaving the lactoferrin contained 1. Kilic, E., Novoselova, M. V., Lim, S. H.,
Pyataev, N. A., Pinyaev, S. I. et al.
within micrometer-sized shells, Formulation for oral delivery of
Microcapsule-protected functional proteins could one day form a key part of human
designed to be stable within lactoferrin based on bovine serum
nutrition. Pictured: Calcium carbonate microparticles. After absorbing a functional albumin and tannic acid multilayer
molecule such as lactoferrin, these microparticles act as the core around which layers of gastric fluid, but to degrade in microcapsules. Scientific Reports 7,
gastro-protective coating can be built. intestinal fluid.” 44159 (2017).

www.research.a-star.edu.sg
The Agency for Science, Technology and Research A*STAR Research is a publication of
(A*STAR) is Singapore’s lead government agency dedicated the Agency for Science, Technology
and Research (A*STAR) — Singapore’s
to fostering world-class scientiﬁc research and talent for a
lead government agency for fostering
vibrant knowledge-based economy. worldclass scientific research.
A*STAR actively nurtures public-sector research and A*STAR Research is published quarterly,
development in biomedical sciences, physical sciences and presenting research highlights and feature
engineering, and spurs growth in Singapore’s key economic articles. All articles are first published
online on the A*STAR Research website
clusters by providing human, intellectual and industrial
and app, and available free to all readers.
capital to our partners in industry and the healthcare sector. Register online to receive the table of
contents by email as each biweekly online
A*STAR currently oversees the following research institutes, issue is published.
consortia and centers and supports extramural research
with universities, hospital research centers, and other local © 2018 A*STAR. This publication may be
reproduced in its original form for personal
and international partners.
use only. Modification or commercial use
without prior permission from the copyright
holder is prohibited.
A*STAR Research is published for A*STAR

Advanced Remanufacturing and Technology Centre (ARTC) by the Partnership and Custom Media unit
Bioinformatics Institute (BII) of Nature Research, part of Springer Nature.
Bioprocessing Technology Institute (BTI)
Editorial
Clinical Imaging Research Centre (CIRC) Agency for Science, Technology
Data Storage Institute (DSI) and Research
Experimental Power Grid Centre (EPGC) 1 Fusionopolis Way, #20-10 Connexis North
Tower Singapore 138632, Singapore
Experimental Therapeutics Centre (ETC)
Genome Institute of Singapore (GIS) Editor-in-Chief David Lane
Institute of Bioengineering and Nanotechnology (IBN) Editorial Board Huck Hui Ng
Institute of Chemical and Engineering Sciences (ICES) Colin Stewart
Evan Newell
Institute of High Performance Computing (IHPC)
Keith Carpenter
Institute for Infocomm Research (I2R) Chandra Verma
Institute of Materials Research and Engineering (IMRE) David Wu
Institute of Medical Biology (IMB) Boris Luk’yanchuk
Patrick Cozzone
Institute of Microelectronics (IME)
Reginald Tan
Institute of Molecular and Cell Biology (IMCB) Nicolas Plachta
National Metrology Centre (NMC) Arseniy Kuznetsov
Singapore Bioimaging Consortium (SBIC) Florent Ginhoux
Managing Editor Adeline Sham
Singapore Institute for Clinical Sciences (SICS)
Administrative Assistant Lay Hoon Tan
Singapore Institute of Manufacturing Technology (SIMTech)
Singapore Immunology Network (SIgN) ISSN 2010-0531
www.research.a-star.edu.sg

A STAR Research October 2017 - December 2017

Transféré par

Informations du document

Titre original

Copyright

Formats disponibles

Partager ce document

Partager ou intégrer le document

Options de partage

Avez-vous trouvé ce document utile ?

Ce contenu est-il inapproprié ?

Droits d'auteur :

Formats disponibles

A STAR Research October 2017 - December 2017

Transféré par

Droits d'auteur :

Formats disponibles

Issue 9 | October - December 2017

Clear. Concise. Convenient.

8 Diagnostic tools in the fast lane

14 Eyes open to a protective mutation

IMAG E HIG H LIG HT

18 A dengue treatment that is one

19 Producing top-notch 2D materials

22 Making HIV drugs work longer

12 20 24 Seeing the big picture

www.research.a-star.edu.sg  A*STAR RESEARCH 1

27 Unraveling the complexity

30 Heavy legacy of Mum’s

31 Unlocking magnetic skyrmions

38 How stomach tumors hide

28 39 Unleashing sulfur’s potential

41 Pancreatic stem cells on tap

48 Better ways with X-rays

2 A*STAR RESEARCH  Issue 9 | October – December 2017

A*STAR Research for 2018, of which have important implications on

A*STAR’s commercialization arm, which A couple of interesting innovations in

www.research.a-star.edu.sg A*STAR RESEARCH 3

4 A*STAR RESEARCH  Issue 9 | October – December 2017

“This all-star cast is

The Asian neTwork for

www.research.a-star.edu.sg A*STAR RESEARCH 5

THE TWO TYPES OF

© intueri/ Getty images

A scan shows reduced

6 A*STAR RESEARCH  Issue 9 | October – December 2017

network also collaborates with is active in diseased heart tissue

www.research.a-star.edu.sg A*STAR RESEARCH 7

to doctors and patients. existing IP that has sufficient check-ups could

8 A*STAR RESEARCH  Issue 9 | October – December 2017

“It is expensive and

www.research.a-star.edu.sg  A*STAR RESEARCH 9

Here a technician does

MAKING BETTER Cutting-edge research

10 A*STAR RESEARCH  Issue 9 | October – December 2017

The DxD Hub is careful to

www.research.a-star.edu.sg  A*STAR RESEARCH 11

12 A*STAR RESEARCH  Issue 9 | October – December 2017

— SUN1 — which locks on

CHROMOSOMES the University of Oklahoma to

MATCH DNA in living sperm precursor

www.research.a-star.edu.sg  A*STAR RESEARCH 13

A leading cause of glaucoma the ocular nerves and tissues.

MUTATION has never been

development of XFS. In XFS, cells association study of exfoliation syn-

14 A*STAR RESEARCH  Issue 9 | October – December 2017

signify a stronger creature than

www.research.a-star.edu.sg A*STAR RESEARCH 15

hair bulb stained with lamin B1 (green),

16 A*STAR RESEARCH  Issue 9 | October – December 2017

— microlissencephaly — carry puzzle.’’ cell cycle, and Pomp was amazed

www.research.a-star.edu.sg  A*STAR RESEARCH 17

A vaccine candidate that blocks an intentionally mutated version

A DENGUE confined to Southeast Asia, the

IS ONE ‘FOUR’ ALL Indonesia, Australasia, Latin

patient that is able to bind to investigate the mechanism

18 A*STAR RESEARCH  Issue 9 | October – December 2017

Molybdenum trioxide (MoO3)

www.research.a-star.edu.sg  A*STAR RESEARCH 19

looked at how the child’s size

www.research.a-star.edu.sg A*STAR RESEARCH 1

2 A*STAR RESEARCH Issue 9 | October – December 2017

www.research.a-star.edu.sg A*STAR RESEARCH 3

4 A*STAR RESEARCH Issue 9 | October – December 2017

www.research.a-star.edu.sg A*STAR RESEARCH 5

6 A*STAR RESEARCH Issue 9 | October – December 2017

www.research.a-star.edu.sg A*STAR RESEARCH 7

8 A*STAR RESEARCH Issue 9 | October – December 2017

www.research.a-star.edu.sg A*STAR RESEARCH 9

10 A*STAR RESEARCH Issue 9 | October – December 2017

www.research.a-star.edu.sg A*STAR RESEARCH 11

12 A*STAR RESEARCH Issue 9 | October – December 2017

www.research.a-star.edu.sg A*STAR RESEARCH 13

14 A*STAR RESEARCH Issue 9 | October – December 2017

www.research.a-star.edu.sg A*STAR RESEARCH 15

16 A*STAR RESEARCH Issue 9 | October – December 2017

www.research.a-star.edu.sg A*STAR RESEARCH 17

18 A*STAR RESEARCH Issue 9 | October – December 2017

www.research.a-star.edu.sg A*STAR RESEARCH 19

20 A*STAR RESEARCH Issue 9 | October – December 2017

www.research.a-star.edu.sg A*STAR RESEARCH 21

22 A*STAR RESEARCH Issue 9 | October – December 2017

www.research.a-star.edu.sg A*STAR RESEARCH 23

24 A*STAR RESEARCH Issue 9 | October – December 2017

www.research.a-star.edu.sg A*STAR RESEARCH 25

26 A*STAR RESEARCH Issue 9 | October – December 2017

www.research.a-star.edu.sg A*STAR RESEARCH 27

28 A*STAR RESEARCH Issue 9 | October – December 2017

www.research.a-star.edu.sg A*STAR RESEARCH 29

30 A*STAR RESEARCH Issue 9 | October – December 2017

www.research.a-star.edu.sg A*STAR RESEARCH 31

32 A*STAR RESEARCH Issue 9 | October – December 2017

www.research.a-star.edu.sg A*STAR RESEARCH 33

34 A*STAR RESEARCH Issue 9 | October – December 2017

www.research.a-star.edu.sg A*STAR RESEARCH 35

36 A*STAR RESEARCH Issue 9 | October – December 2017

www.research.a-star.edu.sg A*STAR RESEARCH 37

38 A*STAR RESEARCH Issue 9 | October – December 2017

www.research.a-star.edu.sg A*STAR RESEARCH 39

40 A*STAR RESEARCH Issue 9 | October – December 2017

www.research.a-star.edu.sg A*STAR RESEARCH 41

42 A*STAR RESEARCH Issue 9 | October – December 2017

www.research.a-star.edu.sg A*STAR RESEARCH 43

44 A*STAR RESEARCH Issue 9 | October – December 2017