U.S. Department of Health and Human Services
Nicholas Guydosh
 

 Contact Info

 
Tel: 301-496-6261
Email: nicholas.guydosh@nih.gov
 

 Select Experience

 
  • Postdoctoral FellowJohns Hopkins University School of Medicine2009-2016
  • Ph.D.Stanford University2009
  • M.PhilUniversity of Cambridge2003
  • A.B.Harvard University2001
 

 Related Links

 

Nicholas R. Guydosh, Ph.D., Stadtman Tenure-Track Investigator

Acting Section Chief, Section on mRNA Regulation and TranslationLaboratory of Biochemistry and Genetics
Specialties
  • Biomedical Engineering/Biophysics/Physics
  • Computational Biology/Bioinformatics/Biostatistics/Mathematics
  • Genetics/Genomics
  • Molecular Biology/Biochemistry
  • Virology
Research Summary/In Plain Language

Research Summary

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.