Project Research Scientist

The Francis Crick Institute

We seek a talented and motivated research scientist  who will train and work in the area of single molecule studies of protein-DNA interactions within Dr Molloy’s Single Molecule Enzymology Laboratory (www.crick.ac.uk/justin-molloy). Dr Molloy’s group pioneered the use of optical tweezers to measure the force and movement produced by individual biological molecules and TIRF microscopy to observe single molecules in living cells. The principal focus of the laboratory is to understand the interchange of chemical and mechanical energy in biological systems. Every living cell contains molecular machines that use chemical energy to drive processes like, cell motility, cell division and DNA replication, transcription and repair. Our ability to observe, track and manipulate individual DNA strands and proteins can give great insights into how the molecules work.

Molloy’s group consists of two scientific support staff, two post-doctoral training fellows and two PhD students. 

The purpose of the current research project is to further our understanding of how anticancer drugs interfere with DNA break repair by targeting poly(ADP-ribose) polymerase-1 (PARP 1). Since the approval of olaparib (AstraZeneca) by the European Medicines Agency in 2014, the inhibition of poly(ADP-ribose) polymerase-1(PARP-1), a key sensor/transducer for DNA damage response, has been shown to be clinically efficacious for the treatment of breast cancer. PARP-1 and other members of its family are involved to varying degrees in the repair of single-stranded and double-stranded breaks and influence various repair pathways, including base excision repair, homologous recombination, classical and altered non-homologous end-joining. By increasing our understanding of the molecular mechanism of PARP’s in the repair pathways, PARP inhibitors might be used more effectively in the clinic by helping to optimize treatment for different patient populations. To this end, we will identify and quantify the effect of these drugs on DNA-binding and poly(ADPribose) transferase (PARylation) activity at DNA break points, using single molecule techniques including total internal reflection fluorescence microscopy and magnetic tweezers (Francis Crick Institute) and atomic force microscopy with Prof Bart Hoogenboom (London Centre for Nanotechnology, University College London). The project will be conducted in partnership with Dr Maria Flocco and Dr Taiana Maia De Oliveira (Astra Zeneca R&D, Cambridge Science Park) and will involve working visits to the different partner laboratories.

The closing date for applications is 16th October 2017 at 23:30 pm.

Please note: all offers of employment are subject to successful security screening and continuous eligibility to work in the United Kingdom.

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