Current Research and Scholarly Interests
UNDERSTANDING SIGNAL TRANSDUCTION NETWORKS The fundamental problem in signal transduction research is to understand how different receptor-stimuli and other cellular inputs control particular cell functions with a high degree of specificity. Similar to the regulation of organ function by complex hormonal feedback mechanisms, it is believed that interactions between several hundred intracellular signaling proteins and many types of second messengers guarantee the specificity of particular cellular responses. The goal of the research is our laboratory is to identify the fundamental properties of such intracellular Signal Transduction Networks and to determine how perturbations in networks can cause disease. In particular, we are currently using three mammalian model systems to understand and model the signaling systems that control neuronal plasticity, chemotaxis and regulated secretion. Many signaling events for these and other cell functions occur as oscillations or all-or-none responses and the precise timing and localization between parallel signaling events is essential for the induction of downstream functions. Therefore, single cell measurements of signaling responses are essential to develop models of signal transduction networks. Over the last years, we have developed several new strategies to monitor signaling events in single cells using different fluorescent microscopy techniques and fluorescent probes and we are now in a unique position to be able to monitor in the same experiment signaling responses in each of many thousands of cells. By combining such imaging techniques with quantitative single cell perturbation strategies, we are pursuing a strategy for a genome-wide exploration on how signaling networks are wired in health and disease.
