Professor Carl Smythe
School of Biosciences
Chair in Cell Biology
Director of the Mass Spectrometry Centre


+44 114 222 4643
Full contact details
School of Biosciences
E03a Florey Building
Firth Court
Western Bank
Sheffield
S10 2TN
- Profile
-
- 2002 – present: Professor of Cell Biology, School of Biosciences, СŷÊÓƵ of Sheffield
- 2004 – 2006: Head of Department, Department of Biomedical Science, СŷÊÓƵ of Sheffield
- 1992 – 2002: Principal Investigator at MRC Protein Phosphorylation Unit, СŷÊÓƵ of Dundee
- 1989 – 1992: American Cancer Society Senior Research Fellow, СŷÊÓƵ of California, San Diego
- 1985 – 1989: British Diabetic Association postdoctoral research assistant at MRC Protein Phosphorylation Group at СŷÊÓƵ of Dundee
- 1981 – 1985: PhD Department of Biochemistry, Trinity College, СŷÊÓƵ of Dublin
- Research interests
-
Chromosome integrity
Chromosomes in eukaryotes control their environment to ensure that genomic integrity is maximised. We are interested in understanding mechanisms of genomic integrity operating at the molecular and cellular level, and determining the consequences when they fail.
Cellular surveillance systems and their role in healthy aging
Research in our laboratory uses molecular cell biology approaches to understand quality control or surveillance mechanisms that operate in cells to ensure fidelity of function, the consequences when they fail, and how they may be exploited to ameliorate disease.
Examples include the replication checkpoint, which operates to ensure that cells experiencing replication stress, can evoke appropriate DNA damage responses, reschedule cell cycle events, or initiate apoptosis, and quality control systems regulating processes involving RNA homeostasis, such as nonsense-mediated decay (NMD), histone mRNA decay (HD), and telomere stability.
We utilise a variety of disease cell models in mechanistic studies and utilise whole genome and new chemical entity (NCE) screening together with mass spectrometry and imaging techniques, coupled with in vitro assays, to synergistically probe both biological and NCE function.
Our chemical biology work focuses on exploring the use of ruthenium co-ordination complexes to explore novel chemical space affecting pathways of interest, as well as novel indole polycyclic derivatives that block NMD.
Our focus is to identify potential new therapeutic targets in relevant disease models, and our work on the replication checkpoint has identified a number of proteins and /or pathways which are of interest.
Future directions
A key focus concerns the functional characterisation of the DNA /RNA helicase Upf1 which acts pleiotropically to regulate NMD, HD and telomere integrity. We have identified a novel NMD inhibitor which, importantly, does not affect histone mRNA regulation or telomere integrity.
We aim to utilise our expertise in genomic integrity and mass spectrometry to identify the target of this inhibitor as a potential therapeutic strategy for the treatment of nonsense mutation-associated disease.
- Publications
-
Show: Featured publications All publications
Featured publications
Journal articles
All publications
Journal articles
Chapters
Conference proceedings papers
- Research group
-
Key collaborators
- Prof Iain Coldham, Dept of Chemistry, СŷÊÓƵ of Sheffield
- Dr James Thomas, Dept of Chemistry, СŷÊÓƵ of Sheffield
- Dr Sarah Danson, Dept of Oncology, СŷÊÓƵ of Sheffield
- Dr Ferdinando Di Cunto, Department of Genetics, Biology& Biochemistry, СŷÊÓƵ of Torino.
- Grants
-
- Cystic Fibrosis Trust
- Yorkshire Cancer Research
- Royal Thai Higher Education Commission
- Malaysia Trust Council (Majlis Amanah Rakyat)
- Teaching activities
-
Undergraduate and postgraduate taught modules
Undergraduate:
- BMS109-106 Pathobiology
- BMS379 Cancer Biology (Co-ordinator)
Masters (MSc):
- BMS6057 Cancer Biology (Co-ordinator)