Postdoctoral Training Fellow – Gene Function (Prof Chris Lord) (ID:155) – London, United Kingdom

Research Lead: Professor Chris Lord 

This position is based in the Gene Function Team (PI Prof. Chris Lord) at the ICR in Chelsea, Central London.

We are seeking a creative and motivated Postdoctoral Training Fellow to study the emergence, prevention and treatment of PARP inhibitor resistance in breast and ovarian cancer. PARP inhibitor resistance can emerge via a number of routes, but the most well-described clinical mechanism is via reversion mutations that restore the function of BRCA1/2 (Pettitt et al., Cancer Discovery 2020; reversions.icr.ac.uk).

The proposed project aims to experimentally characterise BRCA reversion mutations, to determine whether certain pathogenic mutations confer different risks of reversion, and whether genetic background, treatment regime or other interventions can modify reversion risk. This will entail the use of high throughput “tiling” CRISPR mutagenesis (Pettitt et al. Nat Comms 2018), insights from computational analysis of reversions (Pettitt et al. Cancer Discovery 2021) and small molecule DDR inhibitors which may modulate reversion development (Zatreanu et al. Nat Comms 2021). Models used will include cell lines, PDX, PDO and syngeneic mouse models, as well as analysis of sequencing data from human biopsies and ctDNA. The post would suit a candidate with strong CRISPR functional genomics, high throughput cell culture and/or DDR experience.

The ICR has a workforce agreement stating that Postdoctoral Training Fellows can only be employed for up to 7 years as PDTF at the ICR, providing total postdoctoral experience (including previous employment at this level elsewhere) does not exceed 10 years

The Gene Function Laboratory, led by Prof. Chris Lord, focuses upon identifying and understanding tumour specific dependencies, such as synthetic lethal effects, as a means to design novel approaches to treating cancer. We have made major advances in identifying synthetic lethal interactions involving, for example, PARP inhibitors (Farmer et al Nature (2005), Edwards et al Nature (2008), Bajrami et al, Cancer Research (2014)), ATR inhibitors (Williamson et al, Nature Communications (2016)) and ROS1 inhibitors (Bajrami et al, Cancer Discovery (2018)). We aim to generate pre-clinical information that can inform the design of clinical trials and the identification of novel targets for drug discovery programmes.

The Breast Cancer Now Toby Robins Research Centre at the ICR is the first centre in the UK entirely devoted to breast cancer research. Our goal is to advance research into the causes, diagnosis and treatment of breast cancer.

We encourage all applicants to access the job pack attached for more detailed information regarding this role. For an informal discussion regarding the role, please contact stephen.pettitt@icr.ac.uk