From csbi-events at mit.edu Wed Nov 2 08:29:36 2005 From: csbi-events at mit.edu (csbi-events@mit.edu) Date: Wed, 2 Nov 2005 08:29:36 -0500 Subject: [CSBi-events] None Message-ID: Dear CSBi Members: Mark your calendars! CSBi /Whitehead/MIT Symposium Analysis of siRNA data from Imaging-based High Content Screening Shuguang Huang, Ph.D. Eli Lilly Research Laboratories 10.30am Friday November 4th McGovern Auditorium, Whitehead Institute -- Linda K. Earle, Outreach Coordinator Computational and Systems Biology (CSBi) Phone: (617) 324-0074 Fax: (617) 324-0081 Massachusetts Institute of Technology 77 Massachusetts Avenue Building 68 - Room 459 Cambridge, MA 02139 From csbi-events at mit.edu Thu Nov 3 08:50:39 2005 From: csbi-events at mit.edu (csbi-events@mit.edu) Date: Thu, 3 Nov 2005 08:50:39 -0500 Subject: [CSBi-events] CSBi Seminar Series event on Friday, November 4 Message-ID: Dear CSBi Community, This note is being sent simply to remind you of the CSBi Seminar Series event on Friday, November 4. We hope you can attend. Thank you. Dr. Carla Mattos North Carolina State University Department of Molecular and Structural Biochemistry Deciphering Binding Sites on Ras GTPases Friday, November 4, 2005 Maclaurin Building (4-270) 3:00 - 4:00 p.m. Light refreshments served. Abstract Details of the surface of the RasGTPase bound to the GTP analogue GppNHp are studied using two main approaches. The first is through a new crystal form of the protein that presents the switch regions in a very different conformation than observed in the previously published crystal forms. In our new structure the conformation of Switch I superimposes well with the structure observed in the Raps/Raf complex, while the canonical form shows Switch I in the conformation found in the Ras/RasGAP interaction. Both of these forms can be correlated with structures observed in solution by 31P NMR spectroscopy and can be identified by having Tyr 32 in a closed or open conformation respectively. Our structure reveals that Switch II, which adopts multiple conformations in solution, is found in a conformation not previously seen in Ras, but which is similar to the non-catalytic conformation of Ran-GTP stabilized by importin-beta. The structure of the Q61L oncogenic mutant in the new crystal form reveals a network of hydrophobic interactions where Leu61 is stacked against Tyr32 on one side and Tyr64 on the other. These interactions appear to stabilize a non-catalytic form of Ras-GppNHp and may be an important factor in the oncogenic phenotype of the Q61L mutant. The second approach used to study the surface of Ras-GppNHp is called the Multiple Solvent Crystal Structures (MSCS) method. Crystals are crosslinked with gluteraldehyde and transferred to several distinct organic solvent solutions, resulting in a series of crystal structures that can be superimposed for analysis. Using this method we identify two putative sites of protein-protein interaction in Ras away from the Switch regions. The locations of these sites coincide with the clustering of conserved residues in the close family member Ral-GppNHp. Host: Dr. Bruce Tidor Department of Electrical Engineering and Computer Science and Biological Engineering Contact: Brenda Pepe, Biology, 452-3885 http://csbi.mit.edu/ Sponsored by CSBi Annual CSBi Seminar Series in Computational and Systems Biology The entire MIT Community is welcome at this event! -- From csbi-events at mit.edu Wed Nov 9 15:40:48 2005 From: csbi-events at mit.edu (csbi-events@mit.edu) Date: Wed, 9 Nov 2005 15:40:48 -0500 Subject: [CSBi-events] CSBi Seminar Series-Dr. Peter Sorger 11/18/05 Message-ID: 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 -- -- From csbi-events at mit.edu Wed Nov 16 10:29:35 2005 From: csbi-events at mit.edu (csbi-events@mit.edu) Date: Wed, 16 Nov 2005 10:29:35 -0500 Subject: [CSBi-events] (Reminder) CSBi Seminar - 11/18/05 - Dr. Peter Sorger Message-ID: Dear CSBi Community, You may want to take note of the upcoming CSBi Speaker Series Seminar, to be held on Friday, November 18. Please join us if your schedule permits. Thanks. ------------------------------------------------------------------------------------------------ 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 -- -- From csbi-events at mit.edu Wed Nov 23 09:26:25 2005 From: csbi-events at mit.edu (csbi-events@mit.edu) Date: Wed, 23 Nov 2005 09:26:25 -0500 Subject: [CSBi-events] CSBi Speaker Series - Dr. Dan Herschlag 12/2/05 Message-ID: Dear CSBi Community, You may want to take note of the upcoming seminar on Friday, December 2. Thank you. Dr. Daniel Herschlag Stanford University Department of Biochemistry, Beckman Center The Logic of Gene Expression: A Global View of RNA Processing Friday, December 2, 2005 Maclaurin Building (4-270) 3:00 - 4:00 p.m. Light refreshments served. Abstract In the post-genome era, understanding the gene expression program looms as a central fundamental challenge in unraveling the complexities and organization of biological systems. Considerable efforts utilizing whole-genome approaches have revealed complex yet elegant mechanisms for control and coordination at the transcriptional level. Yet a multitude of RNA processing steps occur post-transcriptionally, and these steps, involving both association with RNA-binding proteins and covalent modifications of mRNA and other RNAs, must be dissected to develop and a comprehensive and deep understanding of the mechanisms of gene expression. I will describe our initial global studies of RNA processing events that reveal and suggest aspects of the logic that underlies the gene expression program. References Wang, Y., Liu, C. L., Storey, J. D., Tibshirani, R. J., Herschlag, D. and Brown, P. O. (2002) "Precise and Functional Specificity in mRNA Decay." Natl. Acad. Sci. USA 99, 5860-5865. Arava, Y., Wang, Y., Storey, J. D., Liu, C. L., Brown, P. O. and Herschlag, D. (2003) "Genome-wide Analysis of mRNA Translation Profiles in Saccharomyces cerevisiae." Proc. Natl. Acad. Sci. USA 100, 3889-3894. 106. Gerber, A. P., Herschlag, D. and Brown, P. O. (2004) "Extensive Association of Functionally and Cytotopically Related mRNAs with Puf-family RNA-binding Proteins in Yeast." PLoS Biology. 2, 0342-0354. Host: Dr. David Bartel Biology Department Contact: Laura Resteghini 617.258.7778 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 -- From csbi-events at mit.edu Wed Nov 30 10:17:30 2005 From: csbi-events at mit.edu (csbi-events@mit.edu) Date: Wed, 30 Nov 2005 10:17:30 -0500 Subject: [CSBi-events] (Reminder) CSBi Seminar-Dr. Daniel Herschlag-12/2 Message-ID: Dear CSBi Community, You may want to take note of the upcoming CSBi Speaker Series seminar on Friday, December 2. Please join us if your schedule permits. Thank you. Dr. Daniel Herschlag Stanford University Department of Biochemistry, Beckman Center The Logic of Gene Expression: A Global View of RNA Processing Friday, December 2, 2005 Maclaurin Building (4-270) 3:00 - 4:00 p.m. Light refreshments served. Abstract In the post-genome era, understanding the gene expression program looms as a central fundamental challenge in unraveling the complexities and organization of biological systems. Considerable efforts utilizing whole-genome approaches have revealed complex yet elegant mechanisms for control and coordination at the transcriptional level. Yet a multitude of RNA processing steps occur post-transcriptionally, and these steps, involving both association with RNA-binding proteins and covalent modifications of mRNA and other RNAs, must be dissected to develop and a comprehensive and deep understanding of the mechanisms of gene expression. I will describe our initial global studies of RNA processing events that reveal and suggest aspects of the logic that underlies the gene expression program. References Wang, Y., Liu, C. L., Storey, J. D., Tibshirani, R. J., Herschlag, D. and Brown, P. O. (2002) "Precise and Functional Specificity in mRNA Decay." Natl. Acad. Sci. USA 99, 5860-5865. Arava, Y., Wang, Y., Storey, J. D., Liu, C. L., Brown, P. O. and Herschlag, D. (2003) "Genome-wide Analysis of mRNA Translation Profiles in Saccharomyces cerevisiae." Proc. Natl. Acad. Sci. USA 100, 3889-3894. 106. Gerber, A. P., Herschlag, D. and Brown, P. O. (2004) "Extensive Association of Functionally and Cytotopically Related mRNAs with Puf-family RNA-binding Proteins in Yeast." PLoS Biology. 2, 0342-0354. Host: Dr. David Bartel Biology Department Contact: Laura Resteghini 617.258.7778 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 --