ny times 11-16-07. molecular sciences institute started in 1996 by dr. syndey brenner (2002 nobel...
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![Page 1: NY Times 11-16-07. Molecular Sciences Institute Started in 1996 by Dr. Syndey Brenner (2002 Nobel Prize winner). Opened in Berkeley in 1998. Roger Brent,](https://reader035.vdocuments.site/reader035/viewer/2022062713/56649f3f5503460f94c60426/html5/thumbnails/1.jpg)
NY Times 11-16-07
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Molecular Sciences Institute
• Started in 1996 by Dr. Syndey Brenner (2002 Nobel Prize winner). Opened in Berkeley in 1998. Roger Brent, President and Research Director.
• Create a novel interdisciplinary research environment - new approach not previously envisioned
• Bring together biologists, mathematicians, engineers, computer scientists, physicists, chemists to address fundamental biological problems
• Designated an NHGRI Center of Excellence in Genomic Science in 2002- Center for Genomic Experimentation and Computation and the Alpha Project
• 2006-Became the Center for Quantitative Genome Function
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• How do cells recognize and respond to stimuli or perturbations to produce specific biological outcomes?
CQGF Mission
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Examples
• Cold, drought, growth and development in plants
• Inflammatory response
• Cell proliferation/differentiation
• Others…?
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• Stimulus perceived (receptor)
• Signal propagation
• Physiological response (output)
How do cells to environmental stimulus
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Yeast mating response signaling pathway
• Use as a model system for obtaining a quantitative understanding of signaling systems
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Yeast (Saccharomyces cerevisiae)
• Bakers/brewers yeast• Eukaryote• Complete genome sequenced ~6000 genes• Experimentally tractable• Available genetic and molecular toolkit• Lots of natural genetic variation to exploit
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Yeast mating involves cellular responses to an external
signal• Unicellular organism with three different cell
types (a and haploids and a/ diploids)• During mating haploid cells of opposite
mating type must communicate with each other
• The signaling system through which the presence of mating partner is perceived and propagated is conserved across eukaryotes.
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Cell cycle arrest
Cell morphology
Gene expression
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Systems approach
• Systems biology as the study of the “behavior of complex biological organization and processes in terms of the molecular constituents” Kirschner Cell, 2005
• Interdisciplinary– Molecular genetics – Cell biology– Computational Biology– ‘Omics’ e.g. Proteomics, Transcriptomics, Comparative Genomics– Biochemistry– Modeling
• Systems can be small or large with complex or simple networks and many or few interactions
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Models and Simulations
• Aid our understanding, intuition and reasoning about complex systems
• Allow us to conduct virtual experiments before going into the lab
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•Numbers of molecules and species•Reaction rates•Interactions among protein species (what binds and with what affinity)• Changes in protein modification (e.g. phosphorylation due to activity of kinases and phosphatases)
Measure system-wide parameters
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Measuring system output
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• How does understanding yeast pheromone mating response pathway lead towards understanding of human health and disease?
• By our own estimates ca. 15% of vertebrate coding capacity is devoted to receptors, signaling system components and downstream transcriptional regulatory proteins
• Many diseases result from dysfunction in components of signaling systems
• Many diseases are polygenic and quantitative in nature (e.g. metabolic syndrome/insulin resistance leading to type II diabetes)
• Understanding system function may eventually lead to improved treatments (new drugs/therapies)