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580.

444/644 BIOMEDICAL APPLICATIONS OF GLYCOENGINEERING,


Johns Hopkins BME Department (Spring 2018, 3 credits)
Monday and Wednesday: 12:00 – 1:15 PM; Bloomberg 274

INSTRUCTOR:
Kevin J. Yarema, Smith Building, Room 5029
Telephone: (410) 614-6835
E-mail: kyarema1@jhu.edu

TEACHING ASSISTANT:
Prateek Gowda
Email: pgowda1@jhu.edu

OFFICE HOURS: tbd.

COURSE DESCRIPTION:
This course provides an overview of carbohydrate-based technologies in biotechnology and
medicine. The course will begin by briefly covering basics of glycobiology and glycochemistry
followed by detailed illustrative examples of biomedical applications of glycoengineering. A
sample of these applications include the role of sugars in preventative medicine (e.g., for vaccine
development and probiotics), tissue engineering (e.g., exploiting natural and engineered
polysaccharides for creating tissue or organs de novo in the laboratory), regenerative medicine
(e.g., for the treatment of arthritis or degenerative muscle disease), and therapy (e.g., cancer
treatment). A major part of the course grade will be based on class participation with each
student expected to provide a “journal club” presentation of a relevant paper as well as
participate in a team-based project designed to address a current unmet clinical need that could
be fulfilled through a glycoengineering approach. Recommended Course Background:
EN.580.221 Molecules and Cells;
This course (i.e., 580.444) is recommended for students in the undergraduate BME Cell and
Tissue Engineering focus area; and 580.644 is appropriate for the BME masters Regenerative
and Immune Engineering track. Students from other majors and backgrounds are welcome
provided they have taken an introductory biology and / or biochemistry course.
580.444 and 580.644 meet concurrently; the difference in requirements for the courses is that
students enrolled in the 600-level course are required to serve as “Project Leaders” for grant
proposal preparation. Note that ALL graduate students MUST register for 580.644

COURSE WEBSITE: http://blackboard.jhu.edu


Login using your JHED ID. Note that the two courses are merged such that ALL students should
access the course through 580.444.

REQUIRED TEXT: NONE

REQUIRED READING: “Journal Club” articles (to be posted 2 days in advance of a student
presentation).
SUPPLEMENTAL TEXTS:
1. A. Varki et al., Essentials of Glycobiology (online at
http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=glyco)
2. H.-J. Gabius. The Sugar Code. Available in part at Google Books:
http://books.google.com/books?id=wST5C_JM91AC&lpg=PP1&ots=WmssHIyf3T&dq=the
%20sugar%20code%20gabius&pg=PP1#v=onepage&q&f=false

Note that these textbooks are not required (they’re available online in any event, so you don’t
have to buy them!) but provide good introductory information (Book 1) and more advanced
“basics” (Book 2).

CLASS SCHEDULE:
Date Topic

Jan. 29 Introduction, explanation of course organization and expectations

Jan. 31 Sugar metabolism – Part 1 (Dietary sugar – Glucose and Beyond)

Feb. 5 Sugar metabolism – Part 2 (& start ‘O-GlcNAc’[?])

Feb. 7 O-GlcNAc – Parts 1-3

Feb. 12 O-GlcNAc – Part 4; Student Presentation (tbd)

Feb. 14 O-GlcNAc – Part 5; Student Presentation (tbd)

Feb. 19 N-Glycans – Part 1; Student Presentation (tbd)

Feb. 21 N-Glycans – Part 2; Student Presentation (tbd)

Feb. 26 N-Glycans – Part 3; Student Presentation (tbd)

Feb. 28 N-Glycans – Part 4; Student Presentation (tbd)

Mar. 5 N-Glycans – Part 5; Student Presentation (tbd)

Mar. 7 N-Glycans – Part 6; Student Presentation (tbd)

Mar. 12 Student Presentation (tbd); Student Presentation (tbd)

Mar. 14 Student Presentation (tbd); Student Presentation (tbd)

Mar. 19 No class (Spring Break)

Mar. 21 No class (Spring Break)


Mar. 26 KJY topic: To be determined; Student Presentation (tbd)

Mar. 27 Student Presentation (tbd); Student Presentation (tbd)

Apr. 2 Student Presentation (tbd); Student Presentation (tbd)

Apr. 4 Mid-term exam (move to earlier?)

Apr. 9 KJY topic; tbd (O-glycans or GAGs)

Apr. 11 KJY topic; tbd (O-glycans or GAGs)

Apr. 16 KJY topic; tbd (O-glycans or GAGs)

Apr. 18 Grant presentations, Teams 1 & 2 (A & team) (B & team)

Apr. 23 Grant presentations, Teams 3 & 4 (C & team) (D & team)

Apr. 25 Grant presentations, Teams 5 & 6 (E & team) (F & team)

April 30 Grant presentations, Teams 7 & 8 (H & team) (I & team)

May 2 Grant presentations, Teams 9 & 10 (J & team) (K & team)

GRADING:
Class participation: 30% : (16 x 1%) + (7 x 2%) = 30% based on class attendance and turning in
questions/feedback. The scoring is based on 1% for providing feedback for a student presentation
and 2% for feedback on each grant presentation. Note that regular class attendance is expected
but there is leeway built in for unavoidable absences.
Mid Term exam: 20%
Student presentation: 20% (10% for a 30 minute presentation and 10% for 5 page written
report); students will work in groups of three for this assignment.
Grant application proposal: 20% (5% for LOI, 15% for the class presentation); students will
work in groups of up to five for this proposal (a typical group will have three undergrads and one
or two graduate level students).
Final exam: 10% (the final exam is submission of the written grant proposal by the end of the
day of the scheduled final exam).

DESCRIPTION OF COURSE REQUIREMENTS


Class participation: For student presentations, two twitter type questions/comments (i.e., 140
characters or less!) should be turned in before leaving class. Forms will be provided (or you can
use your own paper).
For the grant the “grant preparation” class sessions, expanded feedback will be required (by
filling in forms that will be provided).

Mid Term exam: Exam questions will be provided in advance (the exam will consist of a subset
of these questions). In a way this will be similar to a “take home” exam except that it will
actually be completed during a class period and answers will be provided w/o notes, reference
materials, etc at that time.

Student presentations:
 The topic should be relevant to ‘biomedical applications of glycoengineering’ (the scope
of the course is covered on the first day; additional guidance is available from the course
instructor or TA). The topic is of the student’s own choosing and should be distinct from
lecture material or grant application projects (it is OK if the topic elaborates on and/or
extends topics briefly covered in class lectures [note that most topics will fit this critera])
and other students’ presentations. Topics (and the choice of presentation data) will be
given priority on a “first come first served” basis.
 Please provide the primary article to the course instructor or TA 48 hours in advance of
your presentation (it will be posted on Blackboard so that your interested classmates can
read it in advance [and thus ask more highly-informed questions . . .. . seriously, one or
two people actually do that! {just kidding, considering that reading these articles is
“required’ everybody does it}]).
 The class presentation should be ~ 35 minutes and consist of (i) ~10 minutes of
background / “overview” material; (ii) ~10 minutes focusing on a specific research study
(i.e., the ‘primary article’ from the previous bullet point) and methods relevant to the
topic; (iii) ~5 minutes for a summary /conclusion; and (iv) ~10 minutes for class
discussion. Each component of the presentation will be graded so be sure to clearly
indicate / ensure that your presentation includes each section.
 The written report should be a maximum of 5 pages in length using 11 or 12 point font
(with single or 1.15 spacing) with figures included in the 6 page limit (it is expected that
about ~ 2 of the 6 pages will be figures); references will not count against the page limit
(note: you MUST cite and format references in a standard manner – i.e., as you would
find in a scientific journal; in addition features usually found in a scientific paper [ e.g.,
and abstract, section headings, etc should be incorporated into your paper]). The written
report will be due on April 17 (or three weeks after your presentation). The paper should
roughly follow the presentation criteria; i.e., ~ 40% introductory/background/big picture
information; ~40% presentation (and critique!) of the research paper; and ~20%
summary/conclusions/future directions. In addition to the report itself, a ½ to 1 page
summary of student feedback should be provided along with how the helpful
criticism/suggestions were incorporated into the report.
 Contributions of each team member should be indicated (as done in many research
articles, examples will be provided)

Grant application proposals: This requirement will produce NIH “R21”-type grants and involve
teams of students led by a 600-level student (i.e., a student enrolled in 580.644). The grant
preparation process will involve formation of teams and selection of a topic in the first two
weeks of the course and subsequently:
The Letter of Intent (LOI) should include a description of the “problem,” its biomedical
significance, and 5 or 6 options (each of which could be shaped into a specific aim) presented in
bullet point form to address this problem. The LOI is limited to one page (in Arial 11 point font;
note that “Arial is the preferred font of the NIH”).
Class Presentation. (guidelines will provided in the “R21” folder on Blackboard).
Written report. (guidelines will provided in the “R21” folder on Blackboard).

Teams (team leader(s) in bold)


Team 1:
Team 2:
Team 3:
Team 4:
Team 5:
Team 6:
Team 7:
Team 8:
Team 9:
Team 10:

Sample topics for student presentations:


Metabolism:
 “glyconutrients” – sham or lifesaver? (or something in between)
 “pharmacokinetics” of dietary sugar utilization by the body (e.g., sucrose vs. glucose vs
HFCS)
 disorders associated with sugar metabolism (e.g., lactose intolerance)
 cancer – the Warburg effect
 cancer – “does sugar feed cancer”?

O-GlcNAc:
 O-GlcNAc and cancer
 O-GlcNAc and epigenetics
 O-GlcNAc and neurological disorders
 O-GlcNAc and cardiovascular disease
 O-GlcNAc and immunity
 O-GlcNAc and diabetes
 O-GlcNAc and development

N-glycans:
 protein folding and quality control:
 implications for recombinant glycoprotein production and activity
 CDGs (congenital disorders of glycosylation)
 cancer (e.g., galectin lattice effects)
 N-glycan diversity (as applied to a specific disease or addressed by computational
modeling)

Miscellaneous
 Role of glycosylation in cell homing (e.g., therapeutic MSCs or HSCs)
 Role of glycosylation in virology
 Role of glycosylation in immunity
 Role of glycosylation in evolution
 Overcoming/avoid -Gal
 Sialic acid-based flu (viral) drugs
 Carbohydrate-based cancer drugs
 Exploiting sLeX therapeutically
 Carbohydrate-based blood thinners
 Role of sialic acid in blood products