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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.
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