Analysis of Biological Networks
MIT Course 20.440
Fall Term 2006
Ram Sasisekharan Room 16-561 258-9494 firstname.lastname@example.org John M. Essigmann Room 56-669 253-6227 email@example.com
James Mutamba Room 56-638 253-6751 jtmutamb@MIT.EDU
Wednesday and Friday, 10:00 – Noon, Room 56-614
3-1-8 H-LEVEL Grad Credit Prereq: 5.07 (or 7.05) or permission of instructors
Aim of the course:
The goal of this course to to provide a student with a view of how pathways network together to enable complex behavior or function. A series of topics are covered, some of which change from year to year, to illustrate the functioning of biological networks. The lectures present examples of complex pathways (chemotaxis, lactation, cytokine mediated intercellular signaling, apoptosis, etc.). In each case emphasis will be placed on how these pathways are regulated at the molecular, cellular and tissue levels.
There will be two examinations during the course, which have the goal of preparing BE graduate students for their qualifying examinations. The end product of the course will be a student team-generated grant proposal. The topic this year will be the design of experiments that probe the synergism between hepatitis viruses and liver diseases, in particular liver cancer. Students will prepare for their topic both out of class and in class during workshops. After each workshop, students will go to the literature and flesh out their ideas as topics for a grant proposal. They will present their ideas to the class in Power Point format during the workshops. After the ideas are fleshed out, the students will jointly write their grant proposal. Each student will write a section of the proposal that will be identified as their own.
Readings will be in the form of primary scientific papers, reviews, and selected chapters from texts.
The proposal will be written in the NSF format http://www.nsf.gov/pubs/2004/nsf042/start.htm or in that used by investigators applying for a grant from the National Institutes of Health.
A more detailed description of the course can be found at this link. The MIT Course Catalog entry is here.
Class participation 25% Examinations and Homework 25% Final written report 50%
Day Date Topic Lecturer Reading/Handout Wednesday September 6 Course introduction
Information flow from DNA to RNA to protein (the central dogma); Review of regulatory circuits and introduction to the concept of evolutionary genomics
JME Course Overview (in pdf format)
Problem Set 1 assigned (due 9/25) Work independently on this problem set
Friday September 8 Information flow and mutation JME
Wednesday September 13
Information flow and mutation. Loss of mismatch repair leads to a hyper-Rec phenotype, which facilitates horizontal gene transfer (antibiotic resistance, etc.)
McAdams, Srinivasan and Arkin, 2004 This paper on evolution of genetic regulatory systems will also introduce the third major topic of the course, chemotaxis
Palen 2006 This article was suggested by a student in the class. Read it for fun -- it shows an interesting twist to the flagellum
Please read the section on DNA structure and base hydrogen bonding properties from a good biochemistry book
Decoding information I (transcription regulation)
Denamur, ... and Radman, 2000 Read as a follow up to the previous paper; this paper shows how the principles in the McAdams paper could be implemented operationally; Also read section on transcription from a good biochemistry book Wednesday September 20
Decoding information II (continued)
JME Read the section on translation from a good biochemistry text Friday September 22 Answer questions regarding Problem Set 1; conclude discussion of translation JME
Kensler, 2003 (overview of liver cancer); Kew, 2001 (hepatitis B infection); Rehermann, 2005 (immunology of HBV and HCV)
Groopman, 2005 (background on aflatoxin and hepatitis as an aid to understanding the Handout below)
Wednesday September 27 Liver disease -- causes and pathway directed possible treatments JME Kuang, 2005 (HBV and aflatoxin as co-risk factors for HCC); Montesano, 2006 (HCC in Africa): Supene and Wain-Hobson, 2005 (HBV and APOBEC) Friday September 29 Examination I Wednesday October 4 Analysis of the interferon network (the JAK/STAT system)
Katze, 2002; Chen, Kuriyan et al., 1998; Look at this web page for a good introduction and great pictures
Read about the Signal Transduction Knowledge Environment;
Friday October 6 Analysis of the interferon network JME
Taniguchi et al., 2001
Wednesday October 11 Analysis of the interferon network
PDB file of STAT1 in a complex with DNA target
Friday October 13 Chemotaxis I -- The Che system; receptor methylation as a mechanism of control of chemotaxis JME Stock, 2003; Levit and Stock, 2002; Alon, Surette, Barkal and Leibler, 1999 Wednesday October 18
Workshop I discussion of student proposal ideas in the area of liver disease (cause, prevention or cure)
JME and RS
Handout (ppt format). Suggestions from a former TA on how to put together your grant application.
Student presentations are here
Friday October 20 Systems biology from the cell to tissue to organism levels of complexity RS Hunter and Borg, 2003; Pawson and Nash, 2003 Wednesday October 25
Workshop II More discussion of student ideas
Chemotaxis II -- How CheY(P) signals to the flagellar motor; chemiosmotic coupling
JME and RS
Also please look at this web site. There is a terrific animation on assembly of the rotary flagellar motor. Friday October 27 Chemotaxis III. How salvage pathways supplement core biochemical pathways; proton pumps JME
Wednesday November 1 Introduction to the extracellular matrix
RS Schmeichel and Bissell; Davies; Dow and Davies (2003); Pamar and Cunha (2004) Friday November 3
Overview of Grant Proposal Process
JME Public Handout from BE Seminar; Other Handout Wednesday November 8 Extracellular matrix 2 RS Friday November 10 NO CLASS Examination 2 handed out on Wednesday-- Due 24 hours later. You must work independently on this assignment RS Wednesday November 15 Epithelial cell morphogenesis signaling hierarchy I RS Taddei (2003); Liu (2004); Brisken (2002); Friday November 17
Epithelial cell morphogenesis signaling hierarchy II
RS Taddei (2003); Liu (2004); Brisken (2002); Wednesday November 22 Epithelial cell morphogenesis signaling hierarchy III RS Taddei (2003); Liu (2004); Brisken (2002);
MMPs Review; Integrin super family; Historical perspective integrin signaling; Cytoskeleton; Apoptosis review; Ram's American Scientist review; Ridley (2003); Lest (2001)
Wednesday November 29
RS and JME Friday December 1 Workshop IV RS and JME Wednesday December 6 Workshop V RS and JME Friday December 8 Workshop VI RS and JME Friday December 15 Final Papers Due
Papers Posted by/for Students:
HB-X protein Tang, 2006 from Luke
Loechler aflatoxin sequence selectivity Benesutti and Loechler, 1988 for Leigh
Smela et al. General review on aflatoxin biology and chemistry
Grant Application Guidelines:
12/3/06 Note: Here are the revised expectations for the final proposal:
The teaching staff proposes the following format for the grant proposal:
1. Ten page written document (not including references), single spaced.
This document would include: One meaty paragraph of Abstract in which you
lay out your vision. One page of Specific Aims. About three pages of
Background. The rest would be Methods and a final paragraph of Perspective.
2. You will then append to your written report the PowerPoint slides
updated from your final presentation. That is, update them to take into
account the questions that were raised in class from your presentation.
3. Please submit your proposals as both Word and pdf documents. To
provide uniformity to the final document, please use 12 point Times
New Roman font.
http://www.nsf.gov/pubs/2004/nsf042/start.htm Final Papers
http//pubs.acs.org/isubscribe/journals/cen/81/i20/html/8120biology.html Good review of Systems Biology from Chemical and Engineering News http://BioCyc.org/ This site is a good way to find out about the pathways we discuss in class. As an example, here is the link to the relevant CheB/CheR steps in the chemotaxis network: http://biocyc.org:1555/new-image?type=ENZYME&object=PHOSPHO-CHEB http://stke.sciencemag.org/ This site links you to the "Signal Transduction Knowledge Environment" (STKE) of Science magazine. This week (9/15) there is a particularly good section on IFNs. You have to enter this site through the MIT Libraries. http://www.cellomics.com/products/hitkit_reagents/related_resources.asp This site has a good animation of chemotaxis. Search for the word chemotaxis. This link will lead you to grant opportunities in the area of Bio-Networks http://grants1.nih.gov/grants/guide/2003/03.10.03/index.html Great link on DNA structure and history Excellent web site by concerning the work of Keiichi Namba -- The flagellar motor Ram Test 1 2 3 4 5 6 7 Very interesting movie from Yoshida and Hisabori on ATP synthase
Last modified: December 05, 2006