Nicholas R. Guydosh, Ph.D.

Stadtman Investigator

Section on mRNA Regulation and Translation, Laboratory of Biochemistry and Genetics

NIDDK

Building 8A, Room 2A04
8 Center Drive
Bethesda, MD 20814

301-496-6261

nicholas.guydosh@nih.gov

Research Topics

Research Goal

We seek to discover how cells control the expression of genes during translation by the ribosome. We’re interested in both the mechanisms that underlie the basic steps of translation—particularly termination and recycling—and how these processes are regulated to carry out cellular functions.

Current Research

The translation of the genetic code is a highly regulated process that is fundamental to life. All cells have evolved elaborate mechanisms for determining which RNA messages get translated, how frequently and where they are translated, and whether errors occur. We employ multi-disciplinary approaches such as ribosome profiling, biochemical techniques, and computational tools to investigate how translation is regulated to control the expression of genes in yeast and mammalian cultured cells. We’re also developing single-molecule fluorescence methods to address mechanistic questions about ribosome function.

We recently discovered that failure of the ribosome recycling factor ABCE1/Rli1 to properly remove ribosomes from mRNAs at stop codons leads to reinitiation of translation in 3’UTRs and the production of short peptides. We’re now investigating the mechanism of this non-canonical process and potential functions for the peptide products in helping cells respond to stress, such as nutrient starvation and viral infection. We’re also interested in the “rescue” process that takes place when ribosomes arrest after translation of particular sequences, such as the poly(A) tail of prematurely polyadenylated mRNAs.

We’re also pursuing general questions of how translation is coupled to mRNA decay and protein localization.

Applying our Research

The ribosome is central to gene expression so our basic work on ribosome function is critical for developing models of disease. In particular, we are examining how changes in the translational machinery during viral infection lead to the production of non-canonical peptides that can be used during the innate immune response. We are also looking at how environmental stress and changes in nutrient levels alter the translational program of a cell. Outcomes of this research will help guide the development of new therapies in the areas of infectious disease, aging, and cancer.

Open Positions

We are interested in hiring motivated and highly talented post-doctoral and post-baccalaureate fellows, particularly those with expertise in protein or nucleic acid biochemistry, mammalian cell culture, genomics and other high-throughput methods, or single-molecule microscopy.

Biography

  • Postdoctoral Fellow, Johns Hopkins University School of Medicine, 2009-2016
  • Ph.D., Stanford University, 2009
  • M.Phil, University of Cambridge, 2003
  • A.B., Harvard University, 2001

Selected Publications

  1. Guydosh NR, Green R. Translation of poly(A) tails leads to precise mRNA cleavage. RNA. 2017;23(5):749-761.

  2. Young DJ, Guydosh NR, Zhang F, Hinnebusch AG, Green R. Rli1/ABCE1 Recycles Terminating Ribosomes and Controls Translation Reinitiation in 3'UTRs In Vivo. Cell. 2015;162(4):872-84.

  3. Woolstenhulme CJ, Guydosh NR, Green R, Buskirk AR. High-precision analysis of translational pausing by ribosome profiling in bacteria lacking EFP. Cell Rep. 2015;11(1):13-21.

  4. Guydosh NR, Green R. Dom34 rescues ribosomes in 3' untranslated regions. Cell. 2014;156(5):950-62.

  5. Guydosh NR, Kimmig P, Walter P, Green R. Regulated Ire1-dependent mRNA decay requires no-go mRNA degradation to maintain endoplasmic reticulum homeostasis in <i>S. pombe</i>. Elife. 2017;6.


This page was last updated on October 3rd, 2017