Michael Stowell - Assistant Professor

Research Profile: Structure and Mechanism at the Chemical Synapse Our research is focused on molecular and supramolecular structures that facilitate communication between neurons at the chemical synapse. We are particularly interested in the architectural arrangement of signaling molecules and characterizing the ways in which such molecular assemblies are formed and undergo changes during synaptic transmission and modulation. Our approach is to investigate individual proteins using x-ray and electron crystallographic methods, and combine this information with 3-D reconstructions of large assemblies along with tomographic analysis of the intact chemical synapse. Our long-term goal is to construct a dynamic molecular and architectural map for the chemical synapse that will help to understand synaptic formation, transmission and plasticity. Ion channel structure and mechanism. Several ion channels are being studied with the goal of determining their molecular mechanism of their action. These include voltage gated channels responsible for propagation and termination of action potentials, calcium channels involved in signal amplification and ligand gated ion channels involved in signal detection and modulation. Using x-ray crystallography and electron microscopy, our goal is to elucidate the high resolution structural elements of these channels in various states. Synaptic architecture, dynamics, and plasticity. Using electron tomographic methods we have begun to study the architecture of the chemical synapse in cultured neurons. Our first goal is to establish the common architectural elements present at the synapse and to identify the molecules involved using specific antibody labeling or genetic tagging. Subsequently, we will investigate the dynamic processes involved in synaptic transmission by stimulating individual neurons and cryogenic trapping them at defined time points post excitation. Ultimately we plan to study long-term, stimulation dependent, synaptic changes in the hope of gaining insight into the architectural elements underlying synaptic plasticity. Formation and mechanisms of supramolecular assemblies. Supramolecular organization and assembly of biomolecules occurs throughout biology. We are interested in supramolecular protein assemblies such as the channel clustering proteins rapsyn and PSD95, and the self assembling GTPase dynamin. The interests and goals of these projects are twofold. First, to understand the role of supramolecular organization and assembly in maintaining and modulating synaptic transmission. And second, the potential of such biomolecular systems to serve as templates for nanomolecular assembly and patterning of materials.