Structure & Function of Biomolecules - Project Work

Along the Structure & Function of Biomolecules course, you will get the opportunity to
study a specific topic related to the course more in-depth in the form of a project work. The
work will be conducted in groups of four students, and include the search for related
information in scientific journals, books and on the internet, summarize your most important
findings in a written report and finally present your work orally to the other students and
teachers. Once you have formed a group, you select a topic based on the list below. Since
several groups may select the same topic, please also select two backup choices. Two groups
will be allowed to have the same topic. Once the topics have been divided between the
groups, you will be informed of your topic and each group will be given a mentor to assist
them throughout the project work.

Below you can find a table describing the different checkpoints in the project work and the
dates for when each part of the work should be finished. Further down you can also find a
description of what is expected from you when carrying out the different tasks.

First you need to form groups and select your projects. Please send an e-mail to Anna
Jansson (anna.jansson@icm.uu.se) at the latest Tuesday November 9, 17:00, containing the
following information:
• Complete names of all members in your group
• e-mail address that you check frequently to each group member
• Three project topics in the order that you prefer them

If you have not found a group by this time, send an e-mail and tell us, so that we can arrange
a group for you.

The topics will then be distributed between the groups, and before 10:00 on Wednesday
November 10, you will receive an e-mail informing you on which topic you have received,
which group you will be collaborating with in exchanging feedback as well as which mentor
you have been appointed.

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 Task what should be done? by when?
Project plan Write project plan, version one. Friday
12/11 17:00
Feedback from mentor on project plan. Monday
15/11 17:00
Final project plan should be approved. Wednesday
17/11 17:00
Written report Completed first draft of written report. Wednesday
1/12 18:00
Feedback on written report by mentor. Friday
3/12 12:00
Incorporate suggestions from mentor and send this version to Monday
both the mentor and opposing group. 6/12 17:00
Give constructive feedback on the written report that you have Wednesday
received from your opposing group. Then send a copy of the 8/12 17:00
report including your feedback to both your opposing group
and your mentor.
Incorporate the feedback from the opposing group into your Thursday
written report, and send to your mentor. 9/12 18:00
Second round of feedback from your mentor. Monday
13/12 17:00
Hand in final version of report to your mentor. Your mentor Wednesday
will make sure that the opposing group receives a copy of the 15/12 10:00
final report.
Presentation Go though oral presentation with your mentor. Wednesday
15/12 16:00
Send final version of your presentation to your mentor. Wednesday
15/12 17:00
Present your work to your fellow students, the mentors and Thursday
teachers. 16/12
Give oral feedback on the written report and the oral 10:15-15:00
presentation of your opposing group.

Project plan
The project plan should about one A4-page (absolute maximum two pages) and must
include:
Title of the project
Names of group members
Aim of the project or question(s) it tries to answer (1 or 2 sentences)
Brief background of the subject of your project
Plan of attack (how are you going to achieve the aim?)

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Report
The written report should be 4-5 A4-pages, but not longer than 5 pages. It should contain
similar information as the project plan, but also more in-depth information and an overview
of the results obtained, a discussion of these results and their interpretation, a set of
conclusions or recommendations, and a list of literature references. A few key figures or
tables can be included. The report should be written in Times New Roman 12pt, single line
space.

Presentation
The presentation on the final day should preferably be done PowerPoint saved in ppt-format.
Make sure you captivate your audience (with blinding science, that is - not with special
effects)! The presentation should not be longer than 15 minutes (to leave 5 minutes for
discussion and feedback from opponents). This means that your presentation should
probably have ~10-20 slides.
The seminar day with the presentations is mandatory! Yes, the whole day! You are not
allowed to bring personal laptops to the seminar day. You are expected to give your full
attention to the presenting group at all times during the day, be active in discussions and ask
questions to the group presenting.

Feedback on other group’s work

You are expected to give constructive feedback on the written report and oral presentation of
another group. When you evaluate the work, try to answer the following questions.
• Is the works clearly described?
• Are the aim, results and conclusions presented in a clear and convincing way?
• Is the language correct grammatically?
• What could be done different to improve the work?
During the project you will get a chance to give written feedback to another group. You will
get a second chance to read the same report just before the oral presentations. On the day of
the presentations you will be expected to give short but well thought through feedback on
both the written report and the oral presentation of your opponent group.

Assessment of you work

The quality of the written report and your oral presentation are very important, but you will
also be assessed on other things. These are: How well you perform as a group, your ability to
give feedback on another group’s work, and how well you incorporated feedback that you
received both from your mentor and from the other group into your report, and how well you
kept all your deadlines, and how you planed the work.

Grading and bonus points

You must obtain a pass on the project work to be able to complete the course. You have
passed when your mentor tells you so. You might need to do additional work on your report
that is not included in the time plan. However, there is also a possibility for you to earn two
bonus points for the exam if you complete the project with distinction. The focus for earning
the bonus points will be the oral presentation, but all parts of the project will be considered.

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Important!
You are most welcome to use any material to find information for your project. However,
two things are crucial
1. You must reference any source you have used for your report.
2. The written text should be your own words. To copy text or use identical wording is
plagiarism, which is strictly forbidden, and will lead to that you fail this part of the course.

Suggested project - Case studies

Objective: to study a subject in detail, with special emphasis on its structural biology
aspects.

Description: There are many topics in the area of structural biology that are fascinating in
themselves but for which there is no time in the course to study them in great detail. In
addition, there are many issues in science, medicine and biotechnology where structural
studies of biomacromolecules play or have played an important role. In these case studies,
you select a topic from the list below and study that in more detail. Find out:
what the medical or scientific or technological importance of the topic is
which biomolecules are involved
what role they play
for which of them structures are known (or could be predicted)
how the molecules of known structure work at the atomic level
what studies have been done to alter their behaviour (mutations, inhibitors, ...)
etc.
The precise scope of your project and the questions you would like to answer depend stongly
on the topic that you choose to study, of course. In some cases, it may be opportune to do
some homology modelling to get a structural hypothesis for a protein whose structure is not
yet known. In others, you may need to do sequence analysis (database searches or multiple
alignments). In all cases, you will need to look at structures you get from the PDB,
determine their fold, active site residues, interaction surfaces, etc.

Snake toxins.
Snake venoms are complicated mixtures of toxins. What do they contain? How do they work
(physiologically and at the molecular level)? What structures are known and what can they
tell you? Which molecules do they interact with? Are any toxin-target complex structures
known?

p53 and cancer.

What is the normal role of this protein and how is it connected with the development of
cancer? What have all the structural studies of this protein taught us about its properties and
the possibilities for a cure?

Antibiotics
What biomolecules are targeted by antibiotics? Which structures are known? How do
antibiotics work at the molecular level? Increasing resistance to current antibiotics is a major
health threat. Why is this? Are new antibiotics being developed? How do they differ from
the current ones?

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Evolution of tRNA synthetases
The two classes of tRNA synthetases are specific for amino acids in a way that appears
symmetric. A hypothesis for their evolution has been presented in TIBS 26 (2001) 591-596.
Use available structures to present and discuss this hypothesis!

Ion and ligand channels

There are many different types of channel and structures are known for quite a few of these.
Select 2-4 different types of channel (e.g., sodium, potassium, mechanosensitive, ...) and
study their architecture and how the structure explains how the appropriate ion or ligand can
be transported. Compare the structures as well. Explain why some channels are highly
specific (e.g., potassium channel) while others are promiscuous (e.g., mechanosensitive
channel).

Clathrin
This is a prime example of form following function. What does clathrin do? What is known
about its structure, symmetry and assembly? What role do the various adaptor proteins play?
What is known about their structures?

Allergies
The PDB contains many structures with different allergens but very few with IgE antibody-
allergen complex. What is known about the cause of allergies and what information is
lacking? There was also one structure published in November 2007 including IgE and an
allergen for bovine milk hypersensitivity. What is new about this structure?

Influenza
One of the first applications of structure-based drug design involved influenza. Which
proteins are involved? What drugs are on the market? How were they developed? How do
they work? Could they play a role in the control of flu pandemics?

AIDS
How does the disease work at the molecular level? Which proteins are involved? What do
they look like? What is their mechanism? Which drugs have been developed? How do they
work? Why is resistance a problem?

Cellulose degradation
Which industrial applications do cellulose degradation have? Which enzymes are involved?
How are they classified? How do they work? How can they be improved?

Caspases - the executioners of apoptosis

Study the phenomenon of programmed cell death (apoptosis). What role do caspases play?
How are they regulated? Each student selects a different caspase structure and studies the
architecture, mechanism, specificity, role in apoptosis, etc.

Chemical warfare
Which agents have been developed? Which molecules do they interact with? How do they
work (physiologically and at the molecular level)? Are any relevant structures known? What
do they tell us?

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Cytochrome P450 enzymes - detoxification and synthesis
How do these enzymes help us stay healthy? How do they affect the effect of medication we
take? Can they harm us? What chemical reaction do they carry out? What useful compounds
do they help synthesize? Pick a few important members of this family (such as CYP3A4 and
P450cam; not necessarily human enzymes). What does the structure look like? What does
the active site look like? What do the structures teach us about the mechanism?

Ricin and the umbrella murder

"On 7 September 1978 the Bulgarian dissident Georgi Markov was stabbed in the leg in
public on Waterloo Bridge in the middle of London by a man using a weapon built into an
umbrella. The weapon embedded a small pellet in Markov's leg that contained ricin. Markov
died four days later." (Source: Wikipedia) Study the structure, function and toxicology of
ricin. How does it work? Find similarities and differences with various bacterial toxins
(cholera toxin, diphtheria toxin, enterotoxin, ...). Could ricin have medicinal applications?

Telomerases
The Nobel Prize in Physiology and Medicine in 2009 was awarded three scientists for their
studies of telomerase. What is the role of telomerases in the cell, and what is known about
the structure and function of the enzyme?

Caspases - the executioners of apoptosis

Study the phenomenon of programmed cell death (apoptosis). What role do caspases play?
How are they regulated? Each student selects a different caspase structure and studies the
architecture, mechanism, specificity, role in apoptosis, etc.

Project Green Light

Green Fluorescent Protein (GFP) is in the news due to the 2008 Nobel Prize in chemistry.
Describe the use of this protein in genetic engineering and in biosensing. Study the structure
and function of the protein and the chromophore.

GTPases in translation
Elongation factor G is a GTPase that catalyzes two steps in the translation cycle:
translocation and ribosome disassembly (good translation review is Schmeing &
Ramakrishnan (2009) Nature 461:1234-42). In human mitochondria, it has recently been
found that these two tasks are catalyzed by two different proteins (Tsuboi et al. (2009),
Molecular Cell 35(4):502-10).
How are these two proteins different? Compare the sequences of human mitochondrial
elongation factor G and ribosome-releasing factor 2 and analyze the differences based on the
available structures of bacterial EF-G and the complex of EF-G with the bacterial ribosome.
Can the differences suggest why these two proteins perform different tasks?

CRISPR - a bacterial immune system

It has recently been discovered that some bacteria and all archea have an inheritable RNA-
based immune system that can protect them against phage infection (reviewed by van der
Oost et al (2009), Trends in Biochemical Sciences 34( 8):401-407). How does this work?
What is structurally known about this system, and what do the available structures explain?