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Edwin Chapman

Faculty: Edwin R. Chapman, PhD

Dept: Professor, Neuroscience
Investigator, Howard Hughes Medical Institute
Contact: 203
Training Areas:
  • Molecular and Cellular Pharmacology
  • Neuroscience
  • Cellular & Molecular Biology
  • Biophysics
  • MD/PhD
  • Physiology
  • Biotechnology
Lab Page: Click Here

Lab Description

Image related to research.

Figure 1. Model of the molecular mechanism of
Ca2+-triggered exocytosis

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.

Image related to research.

Figure 2.Imaging synapses from hippocampal neurons

Our work is also focused on components of the "SNARE-complex", which is thought to form the core of the fusion apparatus. 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 combination of biochemical, biophysical, imaging, spectroscopic and genetic approaches to delineate the interactions/conformational changes that occur during this window of time.

Current experiments include the reconstitution of Ca2+-triggered membrane fusion in vitro, visualization of protein rearrangements and vesicle dynamics inside living cells, genetic manipulations to modulate the efficiency and kinetics of synaptic transmission, and time resolved optical and electrophysiological studies to dissect individual steps in the release pathway and to manipulate the properties of the exocytotic fusion pore.

More recently, we have expanded our efforts to study how changes in membrane trafficking underlie synaptic plasticity and to elucidate the molecular basis for asynchronous synaptic transmission.

Finally, we study the actions of the clostridial neurotoxins, which cause botulism and tetanus poisoning, with emphasis on identifying the pathways of entry, the receptors that mediate entry, and the translocation of the toxins across membranes.

Honors & Awards

Other Positions & Affiliations

Selected Publications: (Find recent publications on PubMed)