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Research Associate in Antibiotic Discovery (Fixed Term)


Applications are invited for a postdoctoral computational biologist to join the Laboratory of Professor Sir Tom Blundell at the University of Cambridge, Department of Biochemistry, Central Cambridge. The successful candidate will work on a project, funded by the Fondation Botnar, to develop new antibiotics for two multidrug-resistant bacterial infections affecting children with Cystic Fibrosis, Pseudomonas aeruginosa and Mycobacterium abscessus. This is a collaborative grant led by clinician and scientist Professor Andres Floto, involving Cambridge scientists in the Chemistry Department (Professor Chris Abell) and Biochemistry (Professor Tom Blundell) and a scientist at the Wellcome Trust Genome Campus (Dr Julian Parkhill).

Research Summary:

The project will focus on developing new antibiotics for children with Cystic Fibrosis (CF) although these will clearly also benefit other children with multi-drug resistant infections. CF affects over 10,000 children and adults in the UK and results in defective ion and water handling by epithelial cells. Most importantly, this impairs muco-ciliary clearance in the lungs and leads to chronic respiratory bacterial infections and ultimately death.

M. abscessus is a multidrug-resistant, rapidly growing species of nontuberculous mycobacteria, which is a major threat to CF individuals and represents the most common and lethal drug-resistant mycobacterial infection in the developed world. Drs. Parkhill and Floto are doing population-level whole genome sequencing and functional phenotyping of clinical isolates of M. abscessus. In collaboration with the chemists and clinical scientists we have successfully begun to apply structure-guided fragment-based approaches to three protein targets of M. abscessus.

The post-doctoral research associate will investigate drug targets and resistance and tolerance mechanisms through computational proteomics. Less than 1% of the ~5000 proteins have structures determined experimentally. We have therefore begun to generate an M. abscessus proteome database - using modeling programs developed in the Blundell group over the past 30 years. The successful candidate will develop new approaches to assigning structural domains and generating models for sequences, corresponding to >60% of the proteome. He/she will identify potential binding cavities and predict hotspots and use our own software to predict the impacts of mutations on protein structure and function, and so identify possible mechanisms of drug resistance. This will provide crucial support for the drug discovery campaigns, and allow in silico chemical screening and cheminformatic predictions for various sub-species and strains of M. abscessus. We will, in parallel develop an equivalent in silico proteome for P. aeruginosa.

Fixed-term: The funds for this post are available for 36 months in the first instance.

To apply online for this vacancy, please click on the 'Apply' button below. This will route you to the University's Web Recruitment System, where you will need to register an account (if you have not already) and log in before completing the online application form.

Any enquires regarding the application process can be directed to Adriana Dote (personnel@bioc.cam.ac.uk).

Informal enquiries about the post can be made to Professor Sir Tom Blundell (tom@cryst.bioc.cam.ac.uk).

Please quote reference PH11884 on your application and in any correspondence about this vacancy.

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Further information

Apply online