Timothy Elston

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Research Interests

• Signal Transduction
• Noise in Gene Expression
• Airway Surface Volume Regulation
• Motor Proteins

Research Synopsis

A main focus of our laboratory is to use computational and mathematical methods to discover and understand control mechanisms used to regulate signaling pathways. In general, signaling pathways are highly nonlinear and inherently noisy systems. They often contain multiple feedback and feedforward loops and share common functional components. Therefore, the broad questions we seek to address are: What biological functions do feedback and feedforward loops provide? Is noise reduction important for maintaining signaling integrity? How is pathway specificity achieved? To answer these questions, we have chosen to study the mating response pathway of yeast S. cerevisiae. This system is arguably the best- characterized signaling pathway of any eukaryote, and it has long served as a prototype for hormone, neurotransmitter, and sensory response systems in humans. We have developed an interdisciplinary research program that combines computational modeling with experimental analysis. Both deterministic and stochastic models of G-protein and protein kinase activity are being developed and validated against experimental data from the Dohlman Lab. The models are used to generate testable hypotheses that define the next generation of experiments.

Publications

Click above for PubMed publications.

• Strychalski, W., Adalsteinsson, D., and Elston, T.C. (2010) Simulating biochemical networks in complex moving geometries. SIAM Journal on Scientific Computing.  (in press).
• Tsygankov, D., Liu, Y., Sanoff, H.K., Sharpless, N.E., and Elston, T.C. (2009) A quantitative model for age-dependent expression of the p16INK4a tumor suppressor.  Proc Natl Acad Sci U S A. 106(39): 16562-16567. Abstract
• Behar, M., Hao, N., Dohlman, H.G., and Elston, T.C.  (2008) Dose-to-duration encoding and signaling beyond saturation in intracellular signaling networks.  PLoS Comput Biol. 4(10): e1000197. [Epub 2008 Oct 10] Abstract
• Zuo, P., Picher, M., Okada, S.F., Lazarowski, E.R., Button, B., Boucher, R.C., and Elston, T.C. (2008) Mathematical model of nucleotide regulation on airway epithelia: Implications for airway homeostasis.  J Biol Chem. 283(39): 26805-26819. Abstract
• Hao, N., Nayak, S., Behar, M., Shanks, R.H., Nagiec, M.J., Errede, B., Hasty, J., Elston, T.C., and Dohlman, H.G. (2008) Regulation of cell signaling dynamics by the protein kinase-scaffold Ste5.  Mol Cell. 30(5): 649-56. Abstract
• Behar, M., Dohlman, H.G., and Elston, T.C.  (2007) Kinetic insulation as an effective mechanism for achieving pathway specificity in intracellular signaling networks.  Proc Natl Acad Sci U S A. 104(41): 16146-51. [Epub 2007 Oct 3] Abstract

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