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.
Recent Publications:
Guido, N., Wang, X., Adalsteinsson, D., McMillen, D., Hasty, J., Elston, T.C., and Collins, J.J. (2006) A bottom-up approach to gene regulation. Nature 439: 856-60. Abstract
Fricks, J., Wang, H., and Elston, T.C. (2006) A numerical algorithm for investigating the role of the motor-cargo linkage in molecular motor driven transport. J Theor Biol 239(1): 33-48. Abstract
Wang, X., Hao, N., Dohlman, H., and Elston, T.C. (2006) Computational and experimental analysis of biostability, stochasticity and oscillations in the mitogen activated protein kinase cascade. Biophys J 90(6): 1961-78. Abstract
Kaern, M., Blake, W., Elston, T.C., and Collins, J.J. (2005) Stochasticity in gene expression. Nat Rev Genet6(6): 451-64. Abstract
Goedecke, D.M., and Elston, T.C. (2005) A model for the oscillatory motion of single dynein molecules.
J Theor Biol 232(1): 27-39. Abstract
Yildirim, N., Hao N., Dohlman, H.G., and Elston T.C. (2004) Mathematical modeling of RGS and G-protein regulation in yeast.
Methods Enzymol 389: 383-98. Abstract
