Overview
The Beckman Institute BNMC brings together researchers from many disciplines at Caltech to address problems in the mechanistic modeling of coupled genomic, intercelullar and intracellular processes. It represents an attempt to encourage closer interaction and collaboration between groups in Biology, Control and Dynamical Systems, and the Center for Advanced Computing Research.
Background and Motivations
Computational methods have found widespread use in many areas of biology, most visibly for applications such as bioinformatics that play to information technology’s strengths in aiding the acquisition, storage and processing of enormous amounts of data. However, quantitative modeling and analysis in cell and developmental biology have had more limited adoption. The principal reason is that modeling problems posed in the context of biology are intrinsically difficult: they often involve multiple time and spatial scales, severe nonlinearities, mixed continuous and discrete variables, mixed deterministic and stochastic processes, complex spatial characteristics, heterogeneous data types, a huge number of components, or various combinations of some or all of these characteristics. Further, biological systems often have a variable structure—the number of compound objects (such as cells or subcellular structures) can change over time, as can their network of relationships with one another, so that model equations change their structure dynamically as well. Perhaps most importantly, realistic models of biological processes will have large uncertainties of all types, from unknown kinetics to poorly characterized mechanisms. All these characteristics challenge existing methods and tools, which makes the application of existing methods a specialty and the development of new ones a priority. 
To address these issues, we formed the BNMC as a coordinated effort aimed at (1) applying existing capabilities to collaboratively solve biological modeling problems that arise in answering scientific questions in Caltech laboratories, (2) exploring a diversity of novel approaches in order to achieve fundamental advances necessary to address the classes of modeling problems biologists want to solve, and (3) organizing projects to better share human experience as well as common infrastructure to avoid duplication and maximize solution interoperability.
Center Vision and Aims
Our focus is biochemical phenomena occurring within and between cells, in particular the mechanistic modeling of molecular networks of all kinds (e.g., transcriptional, regulatory, metabolic, signal transduction, mechanical, etc.) with and without spatial variation and intercellular communication. This is at once one of the oldest areas of modeling in biology and one that continues to challenge theoreticians and biologists alike.
Our long-term vision for the outcome of the center’s work is a coherent theoretical and technological infrastructure supporting the entire cycle from experiment, to modeling, analysis, inference, back to experiment. Our goal is to provide biologists with an integrated computing environment in which they can easily define families of models at any level of structure or detail and then efficiently analyze their properties and relate them back to experimental data to help answer the question, “What is the next experiment that would best differentiate between the current alternative hypotheses?” This is an ambitious vision whose realization is years away, but it serves to set the course for the center.
Over the past fifteen years, we have established expertise and innovation in many areas: detailed modeling collaborations with biologists, development of new theory and mathematical methods, and development of software tools and infrastructure for modeling at the subcellular and multicellular levels. Building on these successes, the BNMC uses challenging biological modeling scenarios as driver problems and pursues simultaneous short-term and long-term strategies designed to exploit tools available now (to offer near-term solutions) and work towards making the long-term vision a reality.
Advisory Board
These ambitious goals would not be possible without involvement from a cross-section of faculty with broad and wide-ranging experience. Luckily, the BNMC has an outstanding Faculty Advisory Board: Barbara Wold, Richard Murray, Mark Stalzer, and Eric Mjolsness. Together they help guide the BNMC and help make its goals a reality.
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