Jeffery Coller
Johns Hopkins University, MD·Biochemistry
To make proteins, cells copy genes into messenger RNA (mRNA), which ribosomes, the cell's protein-making machines, then read. How much protein a cell makes depends both on how fast mRNA is produced and how fast it is destroyed.
- Fields
Biochemistry
Genetics
Biology
- Topics
mRNA stability
mRNA decay
mRNA degradation
- Grants
- 1 known grant, through May 2027
What they work on
- Determine how the mRNA degradation complex senses ribosome speed as it changes with codon optimality.
- Define the molecular events that occur when ribosomes hesitate on slowly read, non-optimal codons and that lead to mRNA decay.
- Investigate how chemical modifications of mRNA change codon optimality and, as a result, mRNA stability.
- Examine how cells change codon optimality by controlling which tRNAs they make, and how this shapes mRNA stability.
More about the research
Some mRNAs last minutes and others hours, and the reasons for this have long been unclear. Coller's lab has shown that the genetic code itself carries part of the answer, through codon optimality. Codons are three-letter 'words' in mRNA, and each is read with the help of a matching transfer RNA (tRNA). Codons whose tRNAs are plentiful, or that pair stably with them, are read quickly ('optimal'). Codons whose tRNAs are scarce are read slowly. The lab found that the mRNA-degrading machinery senses when ribosomes move slowly and destroys those messages. This makes codon optimality a major factor in mRNA stability in yeast and in early development.
Why it matters
Learning how the genetic code controls how long and how fast mRNA messages are read helps explain how cells coordinate gene expression. The grant suggests that cancers and viruses such as H1N1 influenza and SARS-CoV-2 may exploit this hidden layer of the code to take over cell functions. Understanding it could therefore point to new ways of studying these diseases.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
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.
Susan Schroeder
University of Oklahoma, OK·Plant Science & Agriculture
Map dihydrouridine (DHU) on mRNAs at single-nucleotide resolution across tissues and stress conditions in Arabidopsis, using Oxford Nanopore direct RNA sequencing with machine-learning detection algorithms.
Joshua T Mendell
University of Texas Southwestern Medical Center, TX·Biochemistry
Determine how altering dihydrouridine synthase (DUS) activity changes D modifications on tRNAs, overall tRNA metabolism and the PTMD mRNA-decay pathway in human and mouse ccRCC cells.
The school
Johns Hopkins University: 100 labs on PI Pages, $4.1B a year on research, 622 research doctorates a year.
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