Edwin R. Chapman

Ed Chapman Prof Pic
Title
Professor, Department of Neuroscience; Investigator, Howard Hughes Medical Institute
Phone
(608) 263-1762
E-mail
chapman@wisc.edu

Education:

Ph.D. University of Washington

Lab Website:

http://neuro.wisc.edu/chapman/

http://www.hhmi.org/research/membrane-trafficking-neurons-and-presynaptic-aspects-synaptic-transmission

Research Focus:

Molecular Mechanisms of Ca2+-triggered Exocytosis

Research Strengths:

Membrane Excitability and Synaptic Transmission; Molecular Neuroscience

Research Description:

Our research is focused on understanding the structure, function and dynamics of the exocytotic membrane "fusion machine" that mediates the release of neurotransmitters from neurons and hormones from neuroendocrine cells. These studies have begun to reveal insights into how membrane trafficking contributes to neuronal plasticity.

Neuronal exocytosis is triggered by Ca2+ and occurs via the abrupt opening of a pre-assembled fusion pore. Subsequent dilation of the pore results in the complete fusion of the vesicle membrane with the plasma membrane. We are currently identifying and reconstituting the sequential protein-protein and protein-lipid interactions that underlie excitation-secretion coupling. To delineate this pathway, we have primarily focused on the Ca2+-binding synaptic-vesicle protein, synaptotagmin, which appears to function as the Ca2+-sensor that regulates release. Our work is also focused on components of the "SNARE-complex", which is thought to form the core of the fusion apparatus, and on a number of additional regulatory proteins. The rapid kinetics of exocytosis (<1 ms) indicate that only a handful of molecular rearrangements occur to couple Ca2+-synaptotagmin to the opening of the fusion pore. We are using a number of cell biology, genetic and biophysical approaches (chemical genetics, FRET, TIRF, AFM, optical imaging of tags ranging from quantum dots to pHluorins, patch clamp, amperometry, voltammetry etc.) to delineate the interactions/conformational changes that occur during this window of time. Current experiments include the modulation of fusion pores in cultured neurons and model cell lines, reconstitution of Ca2+-triggered membrane fusion in vitro, the visualization of protein rearrangements in vitro and inside living cells, tuning the kinetics of synaptic transmission to affect network function, and the trafficking and fusion of large dense core vesicles that modulate synaptic transmission. Other topics include the mechanism by which clostridial neurotoxins - the agents that cause botulism and tetanus poisoning - enter neurons to block exocytosis, how neuronal polarity is established, and how neurite outgrowth is regulated.

Publications:

Please see PubMed for most recent publications