DESRIPTION (taken from the application): Genomic and biochemical approaches have yielded a wealth of information about cellular components that allow us to design experiments exploring integrated cellular functions. In order to understand the complexities in such integrated cellular functions we need develop in-depth knowledge of the spatio-temporal relationships in the regulation of cell function. At this level we view the cell as a coordinated system of machines capable of collectively producing complex behaviors such as cell motility or synaptic transmission. Interactions between the components of such machinery give rise to properties that only the system as a whole possesses. These properties are called emergent properties and define the capability of the system as a whole. Such systems approach could be useful in explaining complex cellular functions in which a bewildering number of individual molecules are involved. Analyses of complex systems require a combination of experimental and theoretical expertise in biological, mathematical and computer sciences and cannot be done in laboratories of a single discipline much less in individual laboratories. Hence we have formed a multidisciplinary consortium of some thirty laboratories. We need such a group to deal with the explosion of new information in a systematic manner while maintaining detailed expertise in specific areas, a hallmark of individual laboratories. This working group is coordinated at several levels to generate testable hypotheses, collect data, develop functional databases and generate predictive models of higher order cell functions. Eventually, we would like to understand the general design principles of a functional cell. Currently this is not feasible and as a first step towards this goal, we will focus on how specific signaling networks regulate three sets of interconnected functions that exemplify the spatial and temporal complexities in many different cell types. These functions are a) transcription and translation, b) cell movement, extension and contact and c) synaptic communication. These functions can be readily assayed quantitatively in a systematic manner by morphological, biochemical and electrophysiological measurements and members of our group have high expertise in such assays. We have created research laboratories to enable the rapid analysis of these functions in standardized formats. We will also have research facilities that will provide novel reagents and access to emerging technologies. Other members will conduct experiments to bridge the activities of the research laboratories and help develop an integrated model of how cellular machines are coordinately regulated.
