Christopher Fraser
University of California-Davis, CA·Biochemistry
Cells decide which of their messenger RNAs get turned into protein, and those decisions shift fast when conditions change. The step where a messenger RNA is first handed to the ribosome, the molecular machine that reads it, is a major control point, yet how that handoff happens and how it is regulated is still poorly understood.
- Fields
Biochemistry
Biophysics
Genetics
- Topics
translation initiation
mRNA recruitment
ribosome
- Grants
- 1 known grant, through Dec 2028
What they work on
- Determine which intermediate steps of translation initiation act as kinetic checkpoints controlling messenger RNA recruitment, using ensemble fluorescence assays that follow recruitment in real time in a reconstituted human system of purified ribosomes and initiation factors.
- Use single-molecule fluorescence measurements to watch individual messenger RNAs being recruited to the ribosome, resolving sub-second intermediates that are too short-lived for sucrose gradients or immunoprecipitation.
- Test how changing the availability of specific initiation factors, and their post-translational modifications, alters the rate and selectivity of messenger RNA recruitment and start codon selection.
- Validate kinetic models derived from the purified system using translation assays in cell-free extracts and in intact cells, and compare predictions with ribosome profiling measurements of messenger RNA selection.
More about the research
Genome-wide ribosome profiling, which sequences the RNA fragments ribosomes are sitting on, has revealed far more regulation of messenger RNA selection and of which start codon is chosen than was previously appreciated, without explaining the underlying mechanism.
Why it matters
Proteins carry out most of the chemistry life depends on, and faulty control of protein synthesis is linked to the progression of many diseases, including cancers. A mechanistic, quantitative picture of how human ribosomes choose which messages to translate could clarify how those diseases progress and reveal new points in the pathway that drugs could target.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Crystal Conn
University of Pennsylvania, PA·Biochemistry
Map the post-transcriptional layer of gene expression missing from annotated genomes by cataloging alternative ribosome initiation sites, combining unbiased ribosome sequencing with proteomic profiling to define the full oncogenic proteome including unannotated micropeptides.
Jeffery Coller
Johns Hopkins University, MD·Biochemistry
Determine how the mRNA degradation complex senses ribosome speed as it changes with codon optimality.
Fadia Ibrahim
Thomas Jefferson University, PA·Biochemistry
Measure how cellular conditions that stall ribosomes change the mRNA fragments produced by ribothrypsis, using transcriptome-wide sequencing methods that capture both ends of each mRNA.
The school
University of California-Davis: 49 labs on PI Pages, $1.0B a year on research, 647 research doctorates a year.
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