Genes must be regulated to ensure that they are expressed at the right time and place and in the correct amounts. Failure in this process can lead to disease. Genes can be regulated at multiple steps including at the level of mRNA translation, the final step in producing proteins. Work in recent years has revealed that the mis-regulation of mRNA translation is important in the aetiology of a wide range of human diseases including reproductive, neurological and metabolic disorders. Our work examines how mRNAs are regulated at the level of translation and the consequences of their mis-regulation. Current projects in the laboratory investigate translational control events that contribute to reproductive health with a focus towards understanding normal and dysfunctional gametogenesis and early development. This is complemented by our work on host-viral interactions, since studying the mechanisms employed by viruses to subvert the host cell machinery has revealed many of the ways in which cells normally regulate protein production.
Current research projects
- Translational control by the multi-functional Herpes Simplex Virus 1 protein, ICP27.
- Translational regulation in germ cells, the DAZL family of RNA-binding proteins
- Contribution of the poly(A)-binding protein family, central post-transcriptional regulators, to human reproductive health.
2012-2015 BBSRC Project Grant: Elucidating the molecular and biological functions of mammalian-specific PABP5, a unique non-canonical PABP.
2012-2017 MRC Program Grant: Poly(A)-binding proteins highlight the importance of regulated mRNA translation and stability in determining a functional materno-fetal interface.
2011-2014 BBSRC Project Grant: mRNA-specific translational control: A novel mechanism.
2007-2013 Wellcome Trust Project Grant: Translational regulation in germ cells, the DAZL family of RNA-binding proteins
Selected Recent publications
- Friend K, Brook M, Bezirci FB, Sheets MD, Gray NK, Seli E. (2012) Embryonic poly(A)-binding protein (ePAB) phosphorylation is required for Xenopus oocyte maturation. Biochem J. Epub ahead of print
- Brook M, Smith RW, Gray NK. (2012) A Molecular Doorstop Ensures a Trickle through Translational Repression. Cell:149:13-5.
- Brook M, McCracken L, Reddington JP, Lu ZL, Morrice NA, Gray NK. (2012) The multifunctional poly(A)-binding protein (PABP) 1 is subject to extensive dynamic post-translational modification, which molecular modelling suggests plays an important role in co-ordinating its activities. Biochem J. 441:803-12.
- Dinour D, Gray NK, Ganon L, Knox AJ, Shalev H, Sela BA, Campbell S, Sawyer L, Shu X, Valsamidou E, Landau D, Wright AF, Holtzman EJ. (2012) Two novel homozygous SLC2A9 mutations cause renal hypouricemia type 2. Nephrol Dial Transplant. 27: 1035-41.
- Gorgoni B, Richardson WA, Burgess HM, Anderson RC, Wilkie GS, Gautier P, Martins JP, Brook M, Sheets MD, Gray NK. (2011) Poly(A)-binding proteins are functionally distinct and have essential roles during vertebrate development. Proc Natl Acad Sci U S A. 108:7844-9.
- Burgess HM, Richardson WA, Anderson RC, Salaun C, Graham SV, Gray NK. (2011) Relocalisation of cytoplasmic poly(A)-binding proteins 1 and 4 in response to UV irradiation reveals mRNA-dependent nuclear export of metazoan PABPs. J Cell Sci 124:3344-5
- Smith RWP, Anderson RC, Smith JWS, Brook M, Gray NK. (2011) DAZAP1, an RNA-binding protein required for development and spermatogenesis, can regulate mRNA translation. RNA. 17:1282-95.
- Salaun C, MacDonald AI, Larralde O, Howard L, Burgess HM, Lochtie K, Brook M, Malik P, Gray NK, Graham SV. (2010) Poly(A)-binding protein 1 (PABP1) partially relocalises to the nucleus during HSV-1 infection in an ICP27-independent manner and does not inhibit virus replication. J. Virol. 84: 8539-48.
- Vitart V, Rudan I, Hayward C, Gray NK, Floyd J, Palmer CN, Knott SA, Kolcic I, Polasek O, Graessler J, Wilson JF, et al (2008). SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout. Nat Genet 40:437-442
Edinburgh: Richard Anderson, Ian Adams, David Brownstein, Guillermina Girardi, Jane Norman, Alan Wright.
External: Nick Morrice (Glasgow), Sheila Graham (Glasgow), Micheal Sheets (Wisconsin), Emre Seli (Yale), Kent Duncan (Hamburg), Eli Holtzman (Israel)
2010 Post-transcriptional control: mRNA translation, localisation and turnover. Edinburgh, UK.
2009 Gene expression in neuronal disease. Cardiff, UK.
2008 Biochemical Society Triple Focus meeting: Post-transcriptional control. Manchester, UK.
2006 Translation UK. Newcastle, UK.
2001- Organiser of the Scottish RNA club.
2010- Biochemical Society, Member of the Travel Awards Panel.
2009- Biochemical Society, Member of Council.
2009- Biochemical Society, Member of the Meetings Board.
2009- Biochemical Society, Genes Theme panel, Chair.
2009 Site visit panel, Science Foundation Ireland, Dublin.
2009 Tenure panel, CNRS, Rennes.
2008-2009 Biochemical Society, Genes Theme panel, Deputy Chair.
2006-2008 Biochemical Society, Genes Theme panel, Member.
2005 Panel member ‘Women in Science’. Biosciences, Glasgow.
Editorial and Advisory Boards
2009- Biochemical Society Transactions (Editorial Board).
2009 Guest Editor of Biochemical Society Transactions.
2008- Biology of the Cell (Associate Editor).
2008 Guest Editor of Biochemical Society Transactions.
2006-2008 Biology of the Cell (Editorial Advisory Panel).
2006- Biochemical Journal (Editorial Advisory Panel).
2005-2010 Member of the MRC College of Experts.
2003- Faculty of 1000, Biology. Faculty Member for Developmental Biology/Developmental Molecular Mechanisms.