Tuesday, November 3, 2009
101 Stanley Thomas Hall
Tulane University (Uptown)
Refreshments will be served
Tom Bartol, Salk Institute, UCSD
Realistic Modeling of Neuronal Cell Signaling with MCell
Biochemical signaling pathways are integral to the information storage, transmission, and transformation roles played by neurons in the nervous system. Far from behaving as well-mixed bags of biochemical soup, the intra- and inter-cellular environments in and around neurons are highly organized reaction-diffusion systems, with some subcellular specializations consisting of just a few copies each of the various molecular species they contain. For example, glutamtergic dendritic spines in area CA1 hippocampal pyramidal cells contain perhaps 100 AMPA receptors, 20 NMDA receptors, 10 CaMKII complexes, and 5 free Ca++ ions in the spine head. Much experimental data has been gathered about the neuronal signaling pathways involved in processes such as synaptic plasticity, especially recently, thanks to new molecular probes and advanced imaging techniques. Yet, fitting these observations into a clear and consistent picture that is more than just a cartoon but rather can provide biophysically accurate predictions of function has proven difficult due to the complexity of the interacting pieces and their relationships. Gone are the days when one could do a simple thought experiment based on the known quantities and imagine the possibilities with any degree of accuracy. This is especially true of biological reaction-diffusion systems where the number of discrete interacting particles is small, the spatial relationships are highly organized, and the reaction pathways are non-linear and stochastic. Biophysically accurate computational experiments performed on cell signaling pathways is a powerful way to study such systems and to help formulate and test new hypotheses in conjunction with bench experiments.
MCell is a 3D Monte Carlo simulator designed for the purpose of simulating exactly these sorts of cell signaling systems. Here I will present an introduction to the computational algorithms employed in MCell Version 3, and how to use MCell's Model Description Language to build 3D models of virtually any biochemical signaling pathway in the context of its cellular ultrastructure. Finally, I will introduce fundamental concepts of cell signaling processes in organized, compact spaces that have been studied using MCell including: 1) glutamatergic synaptic transmission and calcium dynamics in hippocampal area CA1 dendritic spines; and 2) Presynaptic calcium dynamics and modulation of release probability in Schaffer collateral multisynaptic boutons.
Center for Computational Science, Stanley Thomas Hall 402, New Orleans, LA 70118 email@example.com