Introductory Applied Lecture:

Dr. Ben Eiseman: 1958: faced patients with deadly pseudomembranous colitis
(inflamed colon, caused
by clostridium difficile that produce toxins to break down colon
membranes).
Pseudomembranous Colitus: Inflamed colon, caused by clostridium difficile that
produce toxins to
break colon membranes, and are antibiotic
resistant.
Cure: Used fecal enemas from donor family members through anus of
parents:
reintroduced normal bacteria to the individual with the clostridium
difficile
@Mac Dr. Paul Moayyed: A world leader in fecal enemas treatment.

Applied Lecture:
Theme 1 Lecture 1: Amazing Energy Reserves in Animals

Camel humps are filled with water

- False. Camel humps are filled with a giant mound of fat (80lbs), which allows
for ~2weeks with
limited resources ( C57H110O6)
-Fat is also a source of water (from metabolic processes), but not generally
used for this purpose.
-Allows for long endurance due to: Extreme water-loss tolerance (30-40%),
minimized loss by
condensing water in nostrils and dry feces.

Migrating Geese:
-In spring, they prime themselves 12hrs a day (and even more so before flying
season)
-Leads to increased muscle mass
-Babies do little flights to learn to use resources and fly (prime themselves)
-~50% body mass is lost during flight, most of which are stocked fat
-They somehow can track themselves like a gps would.
Bar Headed Geese:
-Can tap into energy resources in extreme environments
-Extreme high flighters
Dr. Grant McClelland and Doctor Graham Scott: (mac profs that study
high altitude adaptations)
-McClelland: Regulation of lipid oxidation with exercise and environmental
stress
-Exercise is costly, and animals are able to maintain locomotion even in
high altitude or hypoxic
(low oxygen) environments
-High altitude and prolonged flight can induce lipolysis (mobilized
fat transported by
circulation to muscle cells, where its then metabolized by mitochondria,
undergoing
beta-oxidation, turning into Acetyl CoA.
-Humans can break down fat after burning sugar overnight, but
this has consequences
Dr. Scott:
-In high altitudes, the airs thin, so flying requires greater energy
(consequence for aerobic
organisms include the lack of oxygen)

-Organisms must have high respiratory capacity, and breathe at a higher

rate. Their
hemoglobin can also hold more oxygen with larger surface area for
more diffusion, and
more vasculature around muscles (more blood vessels). Therere lots of
mitochondria too.
Energy for migration: Insects (locusts)
-Invasive species in Africa: they decimate agriculture, very high number
of eatings per day,
always consuming, migrate->eat->migrate->eat->migrate.
-They are a trans-atlantic problem that fly over from Africa over the sea.
-Locusts mobilize glucose during first 15 minutes of flight, and consume
them (large
mobilization of lipid is beta-oxydized by their mucles.)
Dr. Kieran Clarke: (oxford university)
-Found that ketone can be converted into acetyl CoA (made energy
drinks from ketone
which tasted like shit) for further catabolism in the krebs cycle.
(process of ketogenesis
includes the breaking down of fat cell into fatty acids)
-Ketone usage also triggers using fat as energy source
-Ketone also reduces hunger, and lessens carbohydrate consumption
Applied Lecture 2: Cystic Fibrosis
Cystic Fibrosis: The most common fatal genetic disease. Mostly affects
digestion and lungs
-Gene affects epithelial (skin-like) parts throughout the body (like
intestine)
-Cause of fatality is lung failure.
-Normally, mucus is a thin lining, but in CF, mucus is green and thick,
and blood is often

mixed from coughing. Males tend to be infertile due to clogging of

vas deferens and
females are infertile, as well. The airway can be seen with lots of
mucus and a lot of
inflammation. Doctors vacuum mucus as treatment, and viewed by
bronchoscopy
Mucus Clearance:
-A cell called cilia is needed to be able to cough mucus out, and
there need be an airway
surface liquid under the mucus (so cilia can beat away at the mucus)
-Goblet Cells: Produce mucus
CFTR genes:
-Discovered in 1989 at Sick Kids Hospital
-They took chunks of DNA and compared them to individuals who had
C.F. They found it
to be on chromosome 7, and by sequencing, found the CFTR genes.
-Protein coded by it moves to apical membrane of cells lining the
airways
-Facilitates transport of Cl- across epithelial membranes. If a
mutation is on the gene,
Cl- transport is messed up and water transport is in imbalance since
water follows the
Na+ (which is attracted by Cl-)
-Cl- isnt transferred, so instead, Na+ comes in, and water follows
the Na+, leading to lack
of water surface above the cilia, and cilia cant wave off the mucus.
CF is a mutation of
missing 3 nucleotides. (deltaF508)
-CFTR mutations affect the number and function of CFTR protein
channels at the cell surface.

-leads to: change in number of CFTR (they get

degraded in the ER, not even
transported), function of protein is compromised
because theyre misshapen
enough to malfunction, but not enough to break
down).
Attempted cures:
-Gene therapy: forcing new copies of genes to replace bad/unwanted
copies of the gene.
-Pharmaceutical Chaperones: drugs to help re-fold the protein, allowing
transport and
function again. (potentiators: fix the protein AT the cell membrane.
Correctors: fix them at
the ER before theyre left. Imagine that potentiators help reach cells
that are doing their
jobs poorly at the cell membranes reach their full potentials
Mac: Dr. Surette: Showed that even good bacteria in upper respiratory
system can lead to
bad consequences in CF patients.
Applied 3: Nearly Universal Genetic Code:
Exceptions: Some ciliates, like Paramecium, UAA and UAG are NOT stop
codons, but code for
glutamine.
-Plastids and mitochondria have their own DNA which code
for proteins
-CUA codes for threonine in yeast mitochondria, but codes
for leucine in
mammalian mitochondria.
Real Life Study: Retinoblastoma

-Disruption of Rb protein (failure to serve as cell cycle

break) leads to cancer on
retinas.
Metastasis: When cancerous cells spread in the body
How does DNA transcription relate to Genetic Abormalities?
-Transcription errors resulted in acquired mutations in the
RNA, which leads to
errors in protein formation. Can result in Diabetes,
Alzhemiers, Aging, and Cancer.
McMaster: Dr. Juliet Daniel:
-Studies transcription factor Kaiso which is a binding
partner for catenin p120ctn
which is abnormally expressed or absent in human breast,
colon, and skin
carcinomas (meaning, when theres cancer in
breast/colon/skin)
- Catenins may function as transcriptional regulators of
genes involved in
tumourigenesis
McMaster: Dr Andre Bedard:
-Studies cell proliferation (growth by multiplication of
parts) and regulatory
mechanisms involved in the maintenance for genome
stability and the
development of the cancer cell.