Edward Twomey
Johns Hopkins University, MD·Biophysics
Nerve cells talk to each other through chemical signals. Many of those signals are received by ligand-gated ion channels: proteins in the cell membrane that open a pore when a specific chemical (the ligand) binds, letting charged ions flow into the cell.
- Fields
Biophysics
Neuroscience
Biochemistry
- Topics
ligand-gated ion channels
AMPA receptors
GluD2
- Grants
- 2 known grants, through May 2031
What they work on
- Determine how AMPA receptors, glutamate-activated channels that carry fast signals between neurons, open and close on a millisecond timescale, using time-resolved cryo-electron microscopy that captures rapid structural snapshots.
- Uncover how auxiliary subunits, helper proteins bound to AMPA receptors, regulate receptor gating and location in cells, using cryo-EM, biophysics and electrophysiology.
- Define how therapeutic molecules alter AMPA receptor function at the molecular level, combining cryo-EM structures with electrophysiological recordings of channel activity.
- Determine how cerebellar ataxia mutations in the amino-terminal and ligand-binding domains of human GluD2, a receptor needed for synapses in cerebellar Purkinje cells, alter its structure, function and pharmacology.
- Reveal how ataxia mutations in the GluD2 transmembrane domain, the part forming the ion pore, disrupt channel activity, using single-channel bilayer recordings, cryo-EM and biochemistry.
More about the research
These channels must open and close within milliseconds, and when they misbehave they contribute to many neurological diseases. The lab asks how these channels work at the level of their atomic structure, how partner proteins and drugs tune them, and how disease mutations break them. Two projects pursue this, one on AMPA receptors and one on the delta-2 receptor.
Why it matters
Faulty ligand-gated ion channels contribute to many neurological diseases. GluD2 mutations are linked to cerebellar ataxia, autism spectrum disorder and schizophrenia, yet no drugs target this receptor. Detailed structural pictures of how AMPA receptors and GluD2 work, how drugs act on them, and how mutations disrupt them could lay the groundwork for structure-based design of future therapies for these disorders.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Christopher Potter
Johns Hopkins University, MD·Neuroscience
Develop methods to harvest functional Ir8a chemosensory receptor complexes directly from roughly 10 million antennae of transgenic Drosophila expressing an EGFP-tagged Ir8a co-receptor.
Show-Ling Shyng
Oregon Health & Science University, OR·Biophysics
Solve cryo-EM structures of pancreatic, cardiac and vascular KATP channels in closed and open states, to build a complete set showing how the channels open in response to ATP and ADP.
Murali Prakriya
Northwestern University, IL·Neuroscience
Map the binding interface between the Orai1 channel and the calcium sensor STIM1. Use photocrosslinking with unnatural amino acids that can be locked in place by light.
The school
Johns Hopkins University: 100 labs on PI Pages, $4.1B a year on research, 622 research doctorates a year.
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