[CSBi-events] CSBi Seminar Series-Dr. Peter Sorger 11/18/05

[csbi-events@mit.edu]

Dear CSBi Community,

You may want to take note of the upcoming seminar on Friday, November 
18.  Thank you.

Dr. Peter Sorger
Massachusetts Institute of Technology
Biology Department

Systems Biology of Cytokine Signaling

Friday, November 18, 2005
Maclaurin Building (4-270)
3:00 - 4:00 p.m.
Light refreshments served.

Abstract
Cytokines and their receptors activate complex signaling cascades 
that regulate cell proliferation, death and differentiation. We are 
developing quantitative, mechanistic models that describe 
cytokine-induced signaling with an eye towards understanding 
cell-type variation and the differences between normal and diseased 
states. We focus on decisions controlled by pro-apoptotic cytokines 
such as Tumor Necrosis Factor (TNF) and TRAIL and pro-survival 
cytokines such as EGF and the insulin-like growth factors (IGF).  By 
mining a compendium comprising ~10,000 measurements of protein 
activities elicited by cytokines individually and in combination we 
have constructed both statistical and physicochemical models of cell 
signaling. Classifier-based regression, in combination with 
experimentation, has established that cells respond to TNF directly, 
via activated TNF receptor, and indirectly via a tri-partite 
autocrine cascade involving transforming growth factor alpha (TGF- 
a), interleukin-1a (IL-1a) and IL-1 receptor antagonist (IL1-ra). 
These cytokines participate in a cell decision processes that plays 
out over 24 hr and adds sequential layers of pro and anti-apoptotic 
signaling to set the level of cell death in a self-limiting fashion.

Experimental work to date has been performed in human tumor cells. 
However, it seems highly likely that TNF-triggered autocrine cascades 
will differ from one cell type to the next.  In this regard, it is 
intriguing that the logic of the TNF-TGF-IL-1a- IL-1ra cascade can be 
re-wired by inflammatory cytokines such as interferons.  

Clinically, it is easier to modulate the activities of extra-cellular 
receptors and their ligands than to inhibit intracellular signaling 
proteins, thanks in part to the development of protein-based 
therapeutics.  By comparing the functions of autocrine cascades in 
normal and diseased cells we believe that it will be possible to 
develop improved strategies for anti-inflammatory and anti-cancer 
therapy.

Host: Dr. Christopher B. Burge
Biology and Biological Engineering
                      
Contact: Brenda Pepe, Biology,
617-452-3885 or pepebe at mit.edu

http://csbi.mit.edu/

Sponsored by  CSBi
Annual CSBi Seminar Series in Computational and Systems Biology
The entire MIT community is welcome to attend!

Directions can be found at the following url:
http://whereis.mit.edu/map-jpg
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