Edwin R Chapman
University of Wisconsin-Madison, WI·Neuroscience
Nerve cells talk to each other by releasing chemical messengers called neurotransmitters, which are stored in tiny membrane bubbles called synaptic vesicles. To release them, a vesicle's membrane must merge with the cell's outer membrane, a process called membrane fusion.
- Fields
Neuroscience
Biophysics
Biochemistry
- Topics
membrane fusion
synaptic vesicles
exocytosis
- Grants
- 2 known grants, through Nov 2032
What they work on
- Measure opening, closing, widening and ion selectivity of single SNARE-formed fusion pores at microsecond resolution, using nanodiscs fused to an artificial lipid membrane and electrical recording.
- Determine the structure of fusion pores between SNARE-bearing nanodiscs by cryo-electron microscopy, using DNA nanostructures to make samples uniform and to control SNARE arrangement.
- Size synaptic vesicle fusion pores in neurons with dyes of different radii to test whether vesicles always fully collapse or sometimes undergo kiss-and-run release.
- Define how each proposed calcium-binding residue in the C2A and C2B domains of synaptotagmin 1 contributes to calcium binding and to release, using isothermal titration calorimetry and iGluSnFR glutamate imaging.
- Test whether synaptotagmin 9 on dense core vesicles controls substance P release in striatal neurons and thereby modulates dopamine release, using knockout neurons, reconstituted fusion assays and striatal slices.
- Compare how synaptotagmin 1 and synaptotagmin 7 drive fast versus slow activity-dependent vesicle docking, using a zap-and-freeze instrument with cryo-electron tomography.
More about the research
The same basic process also drives fertilization, virus entry into cells, and hormone release. How proteins physically force two membranes to merge, and how calcium signals tell them when to do it, are still not fully understood. Two projects address both sides: the mechanics of the fusion pore, and the calcium sensors called synaptotagmins that trigger and tune release.
Why it matters
Neuronal communication is impaired in many mental disorders, and the grants note that dopamine signaling in the striatum plays a key role in addiction and schizophrenia. Clarifying how vesicle fusion works and how its calcium sensors operate could reveal new targets and approaches for conditions where neurotransmitter release goes wrong, and may also inform understanding of membrane fusion in viral entry and fertilization.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Yongli Zhang
Yale University, CT·Biophysics
Reconstitute the full primed SNARE complex, adding complexin and the calcium sensor synaptotagmin-1 to Munc18-1, syntaxin-1, VAMP2 and Munc13-1, and characterize its stability, structure and dynamics on membranes.
John Peters
University of Richmond, VA·Neuroscience
Determine what the poorly characterized N-terminal and linker regions of SNAP-47, a SNARE membrane-fusion protein, contribute to vesicle fusion during AMPA receptor delivery, using an in vitro fusion assay with purified components.
James Robertson
Middle Tennessee State University, TN·Neuroscience
Create new transgenic Drosophila lines that tag the flies' own neuropeptides with fluorescent markers such as mScarlett3, using tissue-specific CRISPR, to confirm that neuropeptides are sorted into dense core vesicles at the mRNA level.
The school
University of Wisconsin-Madison: 91 labs on PI Pages, $1.9B a year on research, 854 research doctorates a year.
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