Eric J Bennett
University of California-San Diego, CA·Biochemistry
Cells constantly make mistakes while copying DNA and building proteins, so a fraction of newly made proteins are defective and potentially toxic. Dedicated quality control systems must recognize these faulty products and destroy them.
- Fields
Biochemistry
Biology
Neuroscience
- Topics
protein quality control
proteostasis
ubiquitin
- Grants
- 1 known grant, through Feb 2028
What they work on
- Determine how terminally stalled and collided ribosomes, the protein-making machines, are sensed and resolved by the spatially restricted quality control pathway the lab identified.
- Test how ribosome-associated quality control pathways can be manipulated to alter overall protein homeostasis, including degradation of defective translation products and recycling of ribosomal complexes.
- Dissect the function of HUWE1, a ubiquitin ligase that tags proteins for destruction, using genome-edited cell lines, engineered HUWE1 variants and the lab's full-length HECT-domain structure.
- Identify HUWE1 substrates and the cellular stress conditions under which cells require HUWE1 for survival and proliferation, establishing how quality control ligases recognize targets under stress.
More about the research
When that surveillance weakens, misfolded proteins accumulate, a hallmark of neurodegenerative disease; when it is unusually strong, it can help cancer cells tolerate heavy mutation loads. The goal here is to work out the molecular rules by which quality control machinery picks out its targets, so that its capacity could eventually be dialed up or down on purpose.
Why it matters
Failures in the systems that remove damaged proteins are tied to neurodegenerative disorders, whose prevalence has doubled over twenty years and is projected to affect more than 13.8 million people in the US by 2050. Understanding how cells recognize defective proteins could point to ways to enhance their clearance in degenerative disease, or to limit quality control capacity in cancer cells that depend on it, and more broadly to extend healthy lifespan.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Michael James Emanuele
University of North Carolina at Chapel Hill, NC·Biochemistry
Define the wave of protein destruction occurring in G2 and at the G2-to-mitosis transition, determining which proteins are degraded and when, and how the phosphate-adding enzyme PLK1 controls this program, using proteomics and cell-based assays.
Stephanie Gates
University of Missouri-Columbia, MO·Biochemistry
Dissect how the Hsp70/CHIP/BAG-1 chaperone complex affects each step of proteasomal degradation, including ubiquitin tagging, substrate binding and breakdown, using in vitro assays with purified proteins.
Jennifer Kong
University of Washington, WA·Biochemistry
Define the principles by which membrane-tethered E3 ubiquitin ligases, enzymes that tag proteins for destruction, recognize and target cell-surface receptors, mapping their target networks with mass spectrometry and biochemistry.
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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