We propose to generate a computer-based model of the development of the C. elegans egg-laying system using state chart-based modeling. The nematode C. elegans is one of the best-defined multicellular animals in existence- anatomically, genetically and molecularly. It is a powerful model system for many fundamental biological processes. The egg-laying system of C. elegans hermaphrodites has been intensively studied in the last two decades, helping to elucidate the development of its four major components as well as the interactions between them. These components include the gonad, the vulva, the egg-laying muscles, and the HSN neurons. The visual formalism of statecharts, within the general framework of """"""""object-oriented modeling"""""""" is a modeling language that is both legible to biologists as well as computer scientists and faithful to the logic of biological systems. Therefore, we will employ this methodology to to model the egg-laying system. Statechart-based formal modeling methods were originally developed by members of our collaboration for the field of system design. As a small-scale biological application of these methods was recently applied to T cell activation. This model served as a feasibility test and integrated phenomena associated with cell-cycle control, signal transduction, cell fate, cell behavior and location. We now propose to extend this to more complex biological phenomena, that will incorporate additional aspects of development including cell fate acquisition, cell migration, axon guidance, and apoptosis. In principle, our model will handle virtually all aspects of development, ultimately allowing our results to be extended to and used by the entire C. elegans community and to other systems as well. By this approach, we hope to pave the way to modeling larger biological events to eventually describe such complex phenomena as the development of all of C. elegans and aspects of human biology and disease progression.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Resource-Related Research Projects (R24)
Project #
1R24GM066969-01
Application #
6557501
Study Section
Special Emphasis Panel (ZRG1-SSS-H (01))
Program Officer
Greenberg, Judith H
Project Start
2003-06-01
Project End
2007-05-31
Budget Start
2003-06-01
Budget End
2004-05-31
Support Year
1
Fiscal Year
2003
Total Cost
$288,853
Indirect Cost
Name
New York University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
041968306
City
New York
State
NY
Country
United States
Zip Code
10012
Kam, Na'aman; Kugler, Hillel; Marelly, Rami et al. (2008) A scenario-based approach to modeling development: a prototype model of C. elegans vulval fate specification. Dev Biol 323:1-5
Sadot, Avital; Fisher, Jasmin; Barak, Dan et al. (2008) Toward verified biological models. IEEE/ACM Trans Comput Biol Bioinform 5:223-34
Fisher, Jasmin; Piterman, Nir; Hubbard, E Jane Albert et al. (2005) Computational insights into Caenorhabditis elegans vulval development. Proc Natl Acad Sci U S A 102:1951-6