A Strategy to Achieve Explanatory, Networked, Mechanistic Models that Link Phenomena within and Between Biological Scales
From E. Cornelius on March 26th, 2018
Friday, February 24, 2012 253 Rhodes Hall Goal: improved, scientific, modeling and simulation methods to be used in providing deeper, medically actionable insight into phenotypic consequences (pharmacological, toxicological) of mechanistically targeted interventions (e.g., a xenobiotic metabolic intervention) within mammalian systems. We need to achieve that goal knowing that there will be individual variability, incomplete system information, and multiple uncertainties. I will describe how achieving that goal requires several necessary and essential model uses. From those uses we specify requirements for engineered in silico devices capable of enabling those uses. Our approach employs formalism-agnostic, object- and agent-oriented methods. I will describe how we developed and used such a device to challenge competing hypotheses about ligand behaviors on leukocyte membranes during rolling and adhesion from molecular, leukocyte, and cell population perspectives. The approach provides a new, potentially important expansion of the scientific method: an independent, scientific means to challenge, explore, better understand, and improve any mechanism and, importantly, the assumptions on which it rests.