David Eliezer
Weill Medical College of Cornell University, NY·Biophysics
Many proteins work without settling into a single fixed shape. These intrinsically disordered proteins stay floppy and keep changing shape, yet they still carry out key jobs in the cell.
- Fields
Biophysics
Biochemistry
Neuroscience
- Topics
tau
Alzheimer's disease
frontotemporal dementia
- Grants
- 2 known grants, through Aug 2029
What they work on
- Determine the structure of a membrane-induced toxic tau oligomer, a small clump of the Alzheimer's-linked protein tau that forms on membranes, using solid-state NMR and ESR spectroscopy.
- Test how lysine succinylation, a chemical tag found on tau in Alzheimer's brains, and acetylation change tau binding to microtubules, tubulin and membranes, using direct and saturation-transfer NMR, cell models and cultured neurons.
- Examine how succinylation and acetylation affect the formation, structure and toxicity of membrane-induced tau oligomers.
- Define how disordered proteins such as alpha-synuclein, metabotropic glutamate receptors and complexins bind membranes, whether by folding into amphipathic helices or by staying disordered, using in vitro structural studies and in vivo functional assays.
- Determine how synapsin condensates, droplet-like protein assemblies, cluster and release synaptic vesicles, and how synucleins and Rab proteins regulate this clustering, combining in vitro and in vivo studies.
More about the research
Some of them also clump together in brain diseases. Their shifting structure makes them hard to study with standard methods. Two projects ask how disordered proteins work when healthy and when they turn toxic. One focuses on tau, a protein central to Alzheimer's disease. The other asks how disordered proteins organize the membranes and small sacs (vesicles) that move material around the cell.
Why it matters
Toxic tau clumps are thought to drive brain-cell death in Alzheimer's disease and related dementias, but their structure has been unknown. A structural picture of these clumps, along with knowing how chemical tags change tau, may reveal new targets for tau-directed drugs. Studying disordered proteins such as alpha-synuclein and synapsin could clarify how neurons store and release the vesicles that carry chemical signals between cells.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
John Straub
Boston University, MA·Biophysics
Identify factors that govern liquid-liquid phase separation and later amyloid aggregation of the disordered proteins tau and alpha-synuclein, combining experiments with computer simulations.
Galia Debelouchina
University of California-San Diego, CA·Biophysics
Determine how heterochromatin protein 1 (HP1), a protein family central to gene silencing, interacts with itself, with chromatin and with partner proteins to set the material properties of heterochromatin compartments.
Lalit Deshmukh
University of California-San Diego, CA·Biochemistry
Determine the structures of ALIX condensates and amyloid fibrils formed by its proline-rich domain, using a new NMR labeling strategy to map interaction hotspots and beta-sheet fibril architecture.
The school
Weill Medical College of Cornell University: 35 labs on PI Pages, $1.6B a year on research, 59 research doctorates a year.
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