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Understanding gene expression: what is the mechanism of nonsense mediated mRNA decay?

Principal Supervisor: Dr Saverio Brogna - School of Biosciences

Co-supervisor: Dr Aditi Kanhee

PhD project title: Understanding gene expression: what is the mechanism of nonsense mediated mRNA decay?

University of Registration: Birmingham

Project outline:

We seek to understand how genes are correctly expressed in eukaryotes. This lab particularly focus on understanding nonsense mediated mRNA decay (NMD), an evolutionary conserved process that serves both as an mRNA surveillance mechanism and a means to regulate gene expression in eukaryotes1. NMD affects the expression of a large fraction of the genome from yeast to human, yet it is not clear what is the mechanism, or possibly multiple mechanisms, that link premature termination to reduced mRNA2. Understanding NMD will be key to a gaining a more satisfactory view of gene expression, moreover, long term it may also have an economic impact on society, specifically, as NMD is a promising drug target for a class of mutations that are linked to human diseases. We study the basic NMD mechanism in fission yeast, which as demonstrated by our earlier publications, the wealth of reagents we have generated and extensive preliminary results that we have (and can share with applicants), is a particularly suitable experimental system. This particular project focuses on understanding the cytoplasmic and nuclear functions of UPF1, and indirectly that of the other two conserved proteins UPF2 and UPF3 that are also required for NMD in essentially all eukaryotes.

References:

  1. Brogna, S. & Wen, J. Nonsense-mediated mRNA decay (NMD) mechanisms. Nat Struct Mol Biol 16, 107-113, doi:10.1038/nsmb.1550 (2009).
  2. Brogna, S., McLeod, T. & Petric, M. The Meaning of NMD: Translate or Perish. Trends Genet 32, 395-407, doi:10.1016/j.tig.2016.04.007 (2016).

BBSRC Strategic Research Priority: Molecules, cells and systems

Techniques that will be undertaken during the project:

  • The project will provide advance training in:
  • Molecular biology
  • Yeast molecular genetics
  • Genomics (analysis of next generation sequencing)
  • Proteomics (high-throughput mass spectrometry)

Contact: Dr Saverio Brogna, University of Birmingham