MODELING

University Of Virginia, Charlottesville VA

Investigators

Linked publications & trials

Abstract

In the first funding phase, the Modeling Initiative constructed a number of relational and biophysical models of[unreadable] mechanics and molecular phenomena related to cell migration and started to develop migration related[unreadable] capabilities within the Virtual Cell (VC) software. This activity can be considered as the last step in the[unreadable] reductionism agenda - in silico reconstitution of a simplified motile system using mathematical representation[unreadable] combining biological knowledge and hypotheses, with determination of the consequences of these hypotheses[unreadable] facilitated beyond human reasoning by means of computer-generated numerical calculations. These models[unreadable] and software development enabled the exciting possibility to make a large, critical step in our quantitative[unreadable] understanding of cell migration from the point of view of systems biology. The models will be standardized from[unreadable] the technical point of view, integrated, comprehensive and predictive. A crucial feature of our endeavor,[unreadable] absolutely required for validating such models and using them for hypothesis prediction-test efforts, is that no[unreadable] modeling is undertaken absent direct input from experimental collaborators. We will describe below the[unreadable] mechanism by which this requirement will be consistently met.[unreadable] The Modeling Initiative will investigate migration mechanisms at the systems-level with a long term goal[unreadable] of developing a comprehensive model of cell migration. This model will have a modular character combining[unreadable] deterministic and stochastic components. Our approach is to develop models for each of the component[unreadable] processes that drive cell migration, e.g.,[unreadable] development of polarity, protrusion,[unreadable] adhesion, and contraction and rear[unreadable] release, and then integrate them into a[unreadable] comprehensive model. For each of these[unreadable] processes, a 'Process Team' that includes[unreadable] both computational biologists and[unreadable] experimental biologists (in a few cases,[unreadable] these capabilities reside within the same[unreadable] laboratory ), will work together to develop[unreadable] a 'Process Model' capable of capturing[unreadable] dynamic behavior in terms of molecular[unreadable] properties (protein levels, states,[unreadable] locations, and activities). It is through this[unreadable] collaborative team that data will be[unreadable] produced, analyzed, and modeled[unreadable] iteratively with a goal of developing[unreadable] additional data from model predictions[unreadable] and using these data to refine the models.