Prof T L Blundell
Applications accepted all year round
About the Project
Academic PhD Supervisor:
Professor Sir Tom Blundell FRS
Department of Biochemistry, Cambridge University, 80 Tennis Court Road, Cambridge CB2 1GA.
Email: [Email Address Removed].
OBJECTIVES: The project aims to describe the structural proteome of either human in relation to cancer or an infectious agent such as mycobacterium tuberculosis, abscessus (in cystic fibrosis) or leprae (leprosy) from prediction of structures, oligomers and complexes based on homology where not experimentally available. The protein structures will be used to define binding sites through definition of hot spots. We will be interested in identifying off-targets in the human infections and in the human proteome as well as the impacts of mutations, especially arising from drug resistance and somatic mutations in cancer using in house software. The research will be in parallel to experimental structure-guided drug discovery using fragment-based methods developed in the Blundell group.
REQUIREMENTS: Applicants must have at least a 2.1 B.Sc. or equivalent degree. Proficiency in programming languages is required. Knowledge of biological systems, structural biology, statistics and bioinformatics is preferred.
Applicants should contact Professor Blundell directly by email at [Email Address Removed], including a statement of why they are interested in this PhD project, a CV giving degree results, further information on IT skills and experience in working in bioinformatics and the names of three academic referees. Projects no longer available for 2017. First availability Oct 2018
Funding Notes
No funding for 2018. Self-funded applicants are welcome to apply.
References
1. Sibanda BL, Chirgadze DY, Ascher DB, Blundell TL (2017) DNA-PKcs structure suggests an allosteric mechanism modulating DNA double-strand break repair. Science 355 (6324), 520-524. [doi: 10.1126/science.aak9654] PMID: 28154079
2. Pires DE, Blundell TL & Ascher DB (2016) mCSM-lig: quantifying the effects of mutations on protein-small molecule affinity in genetic disease and emergence of drug resistance. Sci Rep 6: Art No, 29575 doi:10.1038/srep29575
3. Radoux CJ, Olsson TSG, Pitt WR, Groom CR, Blundell TL (2016) Identifying Interactions that Determine Fragment Binding at Protein Hotspots J. Med. Chem., Article ASAP DOI: 10.1021/acs.jmedchem.5b01980
4. Ochoa-Montano B, Mohan N and Blundell TL (2015) CHOPIN: a web resource for the structural and functional proteome of Mycobacterium tuberculosis Database, 2015, 1–10 doi: 10.1093/database/bav026
5.Pires DEV, Ascher DB, Blundell TL (2013) mCSM: predicting the effects of mutations in proteins using graph-based signatures. Bioinformatics 30(3):335-342 01 Feb 2014 Author URL DOI
6. Surade S, Blundell TL (2012) Structural biology and drug discovery of difficult targets: the limits of ligandability. Chem Biol 19(1): 42-50
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