Inside the Cell Factory: Reverse Engineering of Singla Transduction Pathways
Posted June 01, 2007
Presented By
Overview
Systems biology combines computational or mathematical modeling and experimental analysis to build data-driven numerical representations of biological systems. It then subjects those representations to empirical verification. At a November 1, 2006 meeting of the Systems Biology Discussion Group, Peter Sorger explained how ordinary differential equations can be used to develop a mathematical model describing the signaling pathways of programmed cell death, or apoptosis. Andrea Califano described a novel method for computationally identifying genes that modulate the activity of transcription factors. And Martin Steffen presented an integrative genomic approach that his group is using to elucidate mechanistic information of cytokine signal transduction pathways implicated in chronic obstructive pulmonary disease (COPD).
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Journal Articles
Systems Biology of Life-Death Decisions
Aldridge BB, Burke JM, Lauffenburger DA, Sorger PK. 2006. Physicochemical modelling of cell signalling pathways. Nat. Cell Biol. 8: 1195-1203.
El-Ali J, Sorger PK, Jensen KF. 2006. Cells on chips. Nature 442: 403-411.
Janes KA, Gaudet S, Albeck JG, et al. 2006. The response of human epithelial cells to TNF involves an inducible autocrine cascade. Cell 124: 1225-1239.
Swedlow JR, Goldberg I, Brauner E, Sorger PK. 2003. Informatics and quantitative analysis in biological imaging. Science 300: 100-102.
Gene Modulation of Transcription Factors and the Identification of Drug Targets
Basso K, Margolin A, Stolovitzky G, et al. 2005. Reverse engineering of regulatory networks in human B cells. Nat. Genet. 37: 382-390.
Margolin AA, Wang K, Lim WK, et al. 2006. Reverse engineering cellular networks. Nat. Protoc. 1: 662-671.
Palomero T, Lim WK, Odom DT, et al. 2006. NOTCH1 directly regulates c-MYC and activates a feed-forward-loop transcriptional network promoting leukemic cell growth. Proc. Natl. Acad. Sci. USA 103: 18261-18266.
Wang K, Banerjee N, Margolin AA, et al. 2006. Genome-wide discovery of modulators of transcriptional interactions in human B lymphocytes. Lecture Notes in Computer Science, 3909: 348-362. (PDF, 1.72 MB) FULL TEXT
Coordinating Immune Cell Response in America's #4 Killer
Ahmad R, Nguyen DH, Wingerd MA, et al. 2005. Molecular weight assessment of proteins in total proteome profiles using 1D-PAGE and LC/MS/MS. Proteome Sci. 3: 6 FULL TEXT
Dudley AM, Aach J, Steffen MA, Church GM. 2002. Measuring absolute expression with microarrays with a calibrated reference sample and an extended signal intensity range. Proc. Natl. Acad. Sci. USA 99: 7554-7559. FULL TEXT
Steffen M, Petti A, Aach J, et al. 2002. Automated modelling of signal transduction networks. BMC Bioinformatics 3: 34. FULL TEXT
Speakers
Peter K. Sorger, PhD
Harvard University and Massachusetts Institute of Technology
e-mail | web site | publications
Peter Sorger is a professor of systems biology at Harvard Medical School and holds a joint appointment in MIT's Department of Biological Engineering and Center for Cancer Research. He received his PhD from Trinity College Cambridge, UK, and trained as a postdoctoral fellow with Harold Varmus and Andrew Murray at the University of California, San Francisco. Sorger was cofounder of the MIT systems biology program CSBi, Merrimack Pharmaceuticals, and Glencoe Software and serves on the scientific advisory and corporate boards of several other technology companies. He is currently chair of the CSF study section of the NIH and director of the NIH-NIGMS CDP Center for Systems Biology.
Andrea Califano, PhD
Columbia University
e-mail | web site | publications
Andrea Califano is professor of biomedical informatics at Columbia University, where he leads several cross-campus activities in computational and system biology. Califano is also codirector of the Center for Computational Biology and Bioinformatics, director of the Center for the Multiscale Analysis of Genetic Networks, and associate director for bioinformatics at the Irving Cancer Research Center.
Califano completed his doctoral thesis in physics at the University of Florence and studied the behavior of high-dimensional dynamical systems. From 1986 to 1990, he was on the research staff in the Exploratory Computer Vision Group at the IBM Thomas J. Watson Research Center, where he worked on several algorithms for machine learning, including the interpretation of two- and three-dimensional visual scenes. In 1997 he became the program director of the IBM Computational Biology Center, and in 2000 he cofounded First Genetic Trust, Inc., to pursue translational genomics research and infrastructure related activities in the context of large-scale patient studies with a genetic components.
Martin Steffen, MD, PhD
Boston University
e-mail | web site | publications
Martin Steffen is an assistant professor in the Department of Genetics and Genomics and the Department of Biomedical Engineering at Boston University. His lab works on developing the tools of systems biology for mammalian cells. Steffen received completed an MD/PhD at Stanford University, where he studied the initial photochemical events in photosynthesis. He was a postdoctoral fellow in the laboratory of George Church, where he worked on new technologies for microarrays, mass spectrometry identification of DNA-binding proteins, and the computational prediction of signaling pathways.
Kiryn Haslinger
Kiryn Haslinger is a science writer and editor with a masters in theoretical chemistry. Since working with James D. Watson on his book DNA: The Secret of Life as a research and editorial assistant, she has written freelance articles on science and scientific history.