The cycle of cell growth, DNA synthesis, mitosis and cell division is the fundamental process by which cells grow, develop, and reproduce. Hence, it is of crucial importance to science and human health to understand the molecular mechanisms that control these processes in eukaryotic cells. The control system is so complex that mathematical and computational methods are needed to reliably track the interactions of dozens of genes, mRNAs, proteins, and multiprotein complexes. Deterministic models (ordinary differential equations) are adequate for understanding the average behavior of groups of cells, but to understand the far-from-average behavior of individual cells requires stochastic models that accurately account for noisy events in the growth-division cycle. Noise stems from small numbers of participating molecules within a single cell, and from vagaries of the division process (i.e. unequal partitioning of molecular components between daughter cells). Our group is responsible for the experimental component of a NIH-funded project led by John Tyson (Dpt of Biological Sciences, Virginia Tech) to develop a stochastic model of the cell cycle.
We develop time-lapse microscopy methods to quantify with a single cell
resolution, the abundance of the mRNA and proteins involved in the cell
cycle machinery along with protein-protein interactions. We also
develop data reduction algorithms to extract statistical models that
can be compared to the stochastic model of the cell cycle control.
We also participate in another NIH-funded project led by T.M. Murali (Dpt of Computer Sciences, Virginia Tech). The goal of this project is to develop a framework for generating hypotheses from top-down models, test these hypotheses by integrating them into bottom-up models, and validating the hypotheses using experiments. We are using the control of the cell cycle in yeast as a test case. With an improved understanding of cell cycle regulation in budding yeast, we should be able to suggest novel experiments that provide a better understanding of molecular control systems. We are expecting that the methods developed in this project should be relevant to the study of any complex cellular system, including the development of cancer and the spread of infectious diseases. If we are successful, our project will result in significant advances in computationally driven experimental biology. |
