The University of Southampton
Biological Sciences
Phone:
(023) 8059 4342
Email:
M.Coldwell@soton.ac.uk

Dr Mark J Coldwell BSc(Hons), PhD

Associate Professor, Principal Investigator (Cellular and molecular biosciences)

Dr Mark J Coldwell's photo
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Dr Mark J Coldwell is Associate Professor within Biological Sciences at the University of Southampton.

Career History

2008-Present: Lecturer in Biochemistry. University of Southampton, UK.
2008-Present: Biochemical Society Local Ambassador. University of Southampton, UK.
2001-2008: Postdoctoral Research Fellow. University of Sussex, UK.

Academic Qualifications

1997-2001: PhD in Biochemistry. University of Leicester, UK.
1994-1997: BSc (Hons) in Biological Sciences (Molecular Biology). University of Leicester, UK.

Research

Publications

Teaching

Contributions

Contact

Research interests

Throughout my research career, I have been investigating eukaryotic post-transcriptional control, in particular the initiation phase of translation. This key point in gene expression can rapidly alter the temporal and spatial expression of either the whole transcriptome or specific mRNAs, without requiring new transcription.


Central to translation initiation is the selection of the initiation codon, which is usually an AUG. However, other codons may be used for translation giving rise to N-terminally extended or truncated polypeptides. We are investigating the usage and regulation of these alternative initiation codons in order to examine the importance of alternative initiation codon selection in the generation of protein isoform diversity, a previously neglected aspect of gene expression. This work will modify and extend our understanding of the protein-coding potential of all eukaryotic genomes, as the underlying mechanisms of translational control are conserved across species.


Selection of the correct initiation codon is mediated by several initiation factors, and part of this project explores the regulation of AUG usage versus non-AUG initiation codons. It is clear that the selection of certain initiation codons may have beneficial or detrimental effects on the cell and it is important to establish in which stages of cell growth and/or disease progression that this form of translational control occurs. Deregulation of the appropriate selection of translation initiation codons may be important in the status of certain diseases, including cancer.

Research Projects

Mechanisms of alternative translation initiation codon selection in the regulation of eukaryotic gene expression
In a growing number of cases, initiation codons other than the canonical AUG triplet are used to initiate translation. We are investigating how widespread this phenomenon is, and what it means for current models of initiation.

Transcriptome-wide prediction of eukaryotic translation initiation
Combining bioinformatics searches with experimental data to broaden our knowledge of eukaryotic translation initiation.

Characterisation of BAG-1 as a therapeutic target in HER2 positive breast cancer
Working with colleagues in Medicine, this project aims to decipher the molecular mechanism for changes in BAG-1 expression HER2+ breast cancer.

PhD supervision

Lisa Perry Funded by the BBSRC
The role of alternative translation initiation codons in generating diversity in the proteome.

Alison Donlevy (joint with Prof Graham Packham, FoM), Funded by the Gerald Kerkut Charitable Trust.
Using chemical probes to investigate redox regulation of angiogenesis.

Jim Schofield (joint with Dr Ita O’Kelly, FoM) Funded by the Gerald Kerkut Charitable Trust
Mechanisms of generation and functional significance of novel isoforms of the two-pore domain potassium channel family.

Research group

Molecular and Cellular Biosciences

Research project(s)

Transcriptome-wide prediction of eukaryotic translation initiation

Combining bioinformatics searches with experimental data to broaden our knowledge of eukaryotic translation initiation.

Articles

Additional publications

Morley, S.J. and Coldwell, M.J. (2007) Matters of Life and Death: Translational aspects of apoptosis. in: Mathews, M.B. Sonenberg, N. and Hershey, J.W.B. (eds.) Translational Control in Biology and Medicine, Cold Spring Harbor Laboratory Press, pp 433-458.

Hinton, T.M., Coldwell, M.J., Carpenter, G.A., Morley, S.J. and Pain, V.M. (2007) Functional Analysis of Individual Binding Activities of the Scaffold Protein eIF4G. J. Biol. Chem. 282: 1695-1708.

Coldwell, M.J., Morley, S.J. (2006) Specific isoforms of translation initiation factor 4GI show differences in translational activity. Mol. Cell. Biol. 26: 8448-8460.

Morley, S.J., Coldwell, M.J. and Clemens, M.J. (2005) Initiation Factor Modifications in the Pre‑Apoptotic Phase. Cell Death Differ. 12: 571-84.

Coldwell, M.J. , Hashemzadeh-Bonehi, L., Hinton, T.M., Morley, S.J. and Pain, V.M. (2004) Expression of fragments of translation initiation factor eIF4GI reveals a nuclear localisation signal within the N-terminal apoptotic cleavage fragment N-FAG. J. Cell Sci. 117: 2545-2555.

Mitchell, S.A., Spriggs, K.A., Coldwell, M.J., Jackson, R.J. and Willis, A.E. (2003) The Apaf‑1 internal ribosome entry segment attains the correct structural conformation for function via interactions with PTB and unr. Mol. Cell. 11: 757-771.

Mitchell, S.A., Brown, E.C., Coldwell, M.J., Jackson, R.J. and Willis, A.E. (2001) Protein factor requirements of the Apaf-1 internal ribosome entry segment: roles of polypyrimidine tract binding protein and upstream of N-ras. Mol. Cell. Biol. 21: 3364-3374.

Coldwell, M.J. , deSchoolmeester, M.L., Fraser, G.A., Pickering, B.M., Packham, G. and Willis, A.E. (2001) The p36 isoform of BAG-1 is translated by internal ribosome entry following heat shock. Oncogene 20: 4095-4100.

Coldwell, M.J. , Mitchell, S.A., Stoneley, M., MacFarlane, M., and Willis, A.E . (2000). Initiation of Apaf‑1 translation by internal ribosome entry. Oncogene 19: 899-905.

Stoneley, M., Subkhankulova, T., Le Quesne, J.P.C., Coldwell, M.J., Jopling, C.L., Belsham, G.J., and Willis, A.E. (2000). Analysis of the c-myc IRES; a potential role for cell-type specific trans-acting factors and the nuclear compartment. Nuc. Acids Res. 28: 687-694.

Module Coordinator

BIOL3031 Literature-based research project
BIOL3032 Literature-based research project
BIOL3034 In-depth research project
BIOL3050 Short research project
BIOL2011 Molecular and Cellular Biochemistry: Molecular Cell Biology (Joint coordinator with Dr Matthew Bellamy)

Lecturer

BIOL1007 Macromolecules of Life
BIOL1010 The molecular basis of life
BIOL1005 Cellular & genetic mechanisms
BIOL1006 Cell Biology & Genetics
BIOL2011 Molecular and Cellular Biochemistry
BIOL3015 Regulation of Gene Expression
BIOL3022 Cell Signalling in Health and Disease

Tutor

BIOL1020 Bioanalysis
BIOL2011 Molecular and Cellular Biochemistry: Molecular Cell Biology

Participant in Biological Sciences school outreach and University of Southampton “LifeLab” programmes.

 

 

University of Southampton

Academic Lead for Level 3 open-plan research laboratories in Life Sciences Building 85
Joint coordinator of Biological Sciences external seminar series with Prof Vincent O'Connor
Biochemical Society Local Ambassador for the University of Southampton

Professional responsibilities

Organiser of Translation UK 2012 meeting
Active member of the South Coast RNA Network

Dr Mark J Coldwell
Biological Sciences
Faculty of Natural & Environmental Sciences
Life Sciences Building 85
University of Southampton
Highfield Campus
Southampton
SO17 1BJ

Room Number:85/3051

Telephone:(023) 8059 4342
Email:M.Coldwell@soton.ac.uk

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