This research centers on the application of engineering principles to a set of fundamental problems in cell biology: the biochemical and biophysical mechanisms used by mammalian cells to sense and respond to their environment. Coordinated mathematical modeling and experimental approaches will be used to address two general types of problems in the category of receptor-mediated cell phenomena. First, a quantitative understanding of the mechanisms and kinetics of the processing (transport/reaction/separation) of receptors and their ligands will be developed. Efforts in this area will focus on the intracellular processing of these molecules in endocytosis and the trafficking of these molecules during antigen presentation. Second, the mechanisms and kinetics of biological signal transduction, particularly the involvement of receptors in the inositol trisphosphate/calcium ion signal transduction pathway, will be investigated. An important aspect of cell function is the ability of cells to sense and respond to their environment. This communication between cells and their surroundings is critical to normal cell functioning, to the immune response, and to the action of pharmacologic agents, and is impaired in many disease states. An ability to quantitatively understand and manipulate these communication mechanisms is thus crucial to many areas of modern biotechnology and has application to the maintenance of cell cultures, the development of new pharmaceuticals, and the treatment of disease. In this research, engineering principles will be applied to these fundamental problems in cell biology, with the goal of discovering the relevant mechanisms and kinetics involved in these communication processes.
