Lara Appleby

Logic-based computational modeling of C. elegans development


The first phase of this project consisted of construction of a computational model of C. elegans vulval precursor cell fate specification. The language of Live Sequence Charts and the Play Engine modeling software were used. This model captures mechanistic hypotheses derived from three seminal papers: Sternberg and Horvitz, 1982; Sternberg 1988; and Sternberg and Horvitz, 1989. Simulation of the rule-based model reveal its ability to reproduce essentially all of the experimental observations in the seminal papers. In particular, the model was useful in execution of a rigorous comparison of the long-debated Graded and Sequential signalling hypotheses of fate specification.

Currently the model is being revised so that it will be relatively easy to add details both vertically (i.e. regarding intracellular molecular interactions and dynamics) and horizontally (e.g. regarding gonad development). Developments include modeling the Ras/MAPK pathway components within vulval precursor cells and modeling of an increased variety of genetic perturbations and highly detailed information about molecular interaction during normal development.


References:
P. W. Sternberg, H. R. Horvitz, Cell 44, 761 (Mar 14, 1986).
P. W. Sternberg, Nature 335, 551 (Oct 6, 1988).
P. W. Sternberg, H. R. Horvitz, Cell 58, 679 (Aug 25, 1989).

This project is a collaboration among the following individuals and institutions:

Yale University, New Haven, CT, USA
Michael J. Stern
Lara R. Appleby
Ashish Agarwal

Weizmann Institute of Science, Rehovot, Israel
David Harel
Na'aman Kam

New York University, New York, NY, USA
E. Jane Albert Hubbard
Amir Pnueli
Hillel Kugler