Gheorghe Chistol
Stanford University, CA·Biochemistry·Early-career
Before a cell divides, it must copy its entire genome exactly once. In animals and humans, the genome is so large that copying starts at thousands of sites called replication origins at the same time, moving outward in both directions from each one.
- Fields
Biochemistry
Biophysics
Genetics
- Topics
DNA replication
replication initiation
replication origins
- Grants
- 2 known grants, through Aug 2027
What they work on
- Build a quantitative, real-time picture of how DNA replication starts at origins, using a single-molecule imaging platform that tracks individual replication proteins as they bind DNA.
- Determine the roles of replication initiation proteins and of the protein regions found only in animals, to learn why human factors are two to three times larger than their yeast counterparts.
- Test why disease-linked mutations in replication initiation factors disrupt replication, to understand rare genetic disorders and how cancer cells overactivate initiation.
- Dissect vertebrate replication initiation in Xenopus frog egg extract, combining single-molecule imaging with biochemical, genomic and proteomic methods to find previously unknown regulators.
More about the research
Controlling this start step, replication initiation, is essential for keeping the genome stable. When it goes wrong, the consequences can be serious. Cancer-promoting genes can overactivate initiation to fuel fast cell growth, and mutations in initiation proteins cause rare genetic disorders. Yet how initiation works remains poorly understood, especially in multicellular organisms. It depends on brief contacts between proteins and DNA that standard methods struggle to capture. Also, most detailed studies used yeast, whose key initiation proteins differ greatly from human ones. Some human versions are two to three times larger and contain extra regions of unknown function. Both projects use a single-molecule imaging platform the lab developed, which lets researchers watch individual molecules carry out replication initiation in real time.
Why it matters
Overactive replication initiation helps cancer cells divide rapidly, and mutations in initiation proteins cause rare genetic disorders. By showing how these proteins work and how disease mutations break them, this research could point to replication initiation factors as biomarkers or targets for new cancer therapies. It could also clarify the molecular causes of rare inherited replication disorders.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Joseph J. Loparo
Harvard University, MA·Biochemistry
Determine how core and accessory non-homologous end joining factors cooperate to tether broken DNA ends, using single-molecule imaging of the synaptic complex in a physiological cell-free system.
Yann Chemla
University of Illinois Urbana-Champaign, IL·Biophysics
Determine how contacts with DNA and non-canonical DNA structures control the unwinding activity of the UvrD, Rep and XPD helicases, using optical tweezers combined with fluorescence microscopy.
Craig L Peterson
University of Massachusetts Chan Medical School, MA·Biochemistry
Define the step-by-step mechanism by which the SWR1C remodeler places the histone variant H2A.Z into nucleosomes, using ensemble and single-molecule fluorescence assays.
The school
Stanford University: 87 labs on PI Pages, $1.6B a year on research, 739 research doctorates a year.
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