Lalit Deshmukh
University of California-San Diego, CA·Biochemistry
Some proteins can switch between being dissolved, forming liquid-like droplets, and forming rigid fibers, and cells may use these switches to control what the proteins do. This project studies such a switch in ALIX (also called PDCD6IP), a human protein involved in cell signaling, programmed cell death, the budding of viruses from cells, and pinching off cell membranes.
- Fields
Biochemistry
Biophysics
Chemistry
- Topics
phase separation
biomolecular condensates
amyloid fibrils
- Grants
- 1 known grant, through Jul 2027
What they work on
- 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.
- Test how tyrosine phosphorylation and dephosphorylation and lipid membranes regulate ALIX condensates and fibrils, including which tyrosines trigger polymerization and how a kinase reaches its target sites.
- Examine whether ALIX polymerizes in mammalian cells and how polymerization changes ALIX's cellular functions.
- Uncover how liquid-like ALIX condensates harden into rigid fibrils over time, using mechanistic studies of this maturation process.
- Characterize how ALIX binds ubiquitin and how ubiquitination interacts with phosphorylation-driven polymerization, using structural and kinetic studies of purified ubiquitinated ALIX.
More about the research
ALIX's many jobs are controlled by chemical tags added after the protein is made, especially phosphate groups on tyrosine amino acids and the small protein ubiquitin.
Why it matters
ALIX helps run essential cell processes, including membrane pinching and the budding of enveloped viruses. This basic work will explain how chemical tags turn ALIX's droplet and fiber states on and off. It could also clarify more generally how liquid-like protein droplets mature into amyloid fibrils, a type of structure linked to disease.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
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.
David Eliezer
Weill Medical College of Cornell University, NY·Biophysics
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.
Wei Qiang
Binghamton University, NY·Biophysics
Test proposed mechanistic models of local membrane leakage caused by on-pathway beta-amyloid fibril intermediates in liposomes, using solid-state NMR and signal-enhancing dynamic nuclear polarization.
The school
University of California-San Diego: 84 labs on PI Pages, $1.9B a year on research, 637 research doctorates a year.
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