Michael Stowell

Molecular, Cellular & Developmental Biology; Member of the Center for Neuroscience

Department of Molecular, Cellular & Developmental Biology
Campus Box 347
Porter Biosciences
University of Colorado at Boulder
Boulder, CO 80309-0347

email: Michael.Stowell@colorado.edu
Phone: 303-735-2983
FAX: 303-492-7744
Website: http://spot.colorado.edu/~stowellm/

Dr. Stowell’s research is focused on molecular and supramolecular structures that facilitate communication between neurons at the chemical synapse. He is particularly interested in the architectual arrangement of signalling molecules and enzymes, and characterizing the ways in which such molecular assemblies are formed and undergo changes during synaptic transmission and modulation. His approach is to investigate individual proteins using x-ray and electron crystallographic methods and to combine this information with EM images obtained via 3-D reconstruction of supramolecular assemblies and tomographic analysis of the intact chemical synapse. His 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 plan of determining the 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 rapid affinity purification methods, along with x-ray crystallography and electron microscopy, Dr. Stowell’s goal is to illucidate the structural elements of these channels in various states.

Synaptic architecture, dynamics, and plasticity. Using electron tomographic methods Dr. Stowell has begun to study the architecture of the chemical synapse in cultured neurons. His first goal is to establish the common architectual elements present at the synapse and to identify the molecules involved using specific antibody labelling or genetic tagging. Subsequently, he will perform field potential stimulations coupled with cryogenic trapping to investigate the dynamic processes involved in synaptic transmission. Ultimately Dr. Stowell plans to study long-term, stimulation dependent, synaptic changes in the hopes of gaining insight into the architectual elements underlying synaptic plasticity.

Formation and mechanisms of supramolecular assemblies. Supramolecular organization and assembly of biomolecules occurs throughout biology. Dr. Stowell is interested in supramolecular protein assemblies such as the channel clustering proteins rapsyn and PSD95, the self assembling GTPase dynamin, as well as the viral coat protein of tobacco mosaic virus. 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.

Selected Publications:

Marks, B., M.H., Stowell, Y. Vallis, I.G. Mills, A. Gibson, C.R. Hopkins, and H.T. McMahon (2001) GTPase activity of dynamin and resulting conformational change are essential for endocytosis. Nature 410:231-235.

Stowell, M.H., B. Marks, P. Wigge and H.T. McMahon (1999) Nucleotide dependent conformational changes in dynamin: Evidence for a mechanochemical molecular spring. Nature Cell. Biol. 1(1):27-32.

Miyazawa, A., Y. Fujiyoshi, M.H.B. Stowell and N. Unwin (1999) Nicotinic acetylcholine receptor at 4.6 (tm) resolution: Transverse tunnels in the chanel well. J. Molec. Biol. 288(4):765-786.

Stowell, M.H.B., A. Miyazawa and N. Unwin (1998) Macromolecular structure determination by electron microscopy: New advances and recent results. Curr. Op. Struct. Biol. 8(5):595-600.