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Postdoctoral Research Scientist - Ref. SC-CRUK1-Resist Understanding and overcoming resistance to MEK1/2 inhibitors in tumour cells Job Description Tumour cells with RAS or BRAF mutations frequently adapt to be addicted to MEK1/2-ERK1/2 signalling making inhibitors of this pathway attractive anti-cancer therapeutics. Despite this tumour cells can quickly develop acquired resistance to such drugs, limiting their clinical benefit. Understanding mechanisms of acquired drug resistance is important for two reasons. First, it may allow the development of rational drug combination strategies that allow resistance to be delayed or overcome. Second, from a basic biology perspective, investigating mechanisms of acquired resistance to targeted signal pathway inhibitors often uncovers new information about key pathway control points and cross-talk with other pathways. Using novel and established models this project will define novel mechanisms of acquired resistance to MEK1/2 inhibitors and seek to develop strategies to delay or overcome it. This position is funded by Cancer Research UK, includes collaborations with AstraZeneca and the Wellcome Trust Sanger Institute and is a limited term contract with funding available for up to 19 months. For recent relevant references from the lab see:1. Wickenden JA et al (2008) Colorectal cancer cells with the BRAFV600E mutation are addicted to the ERK1/2 pathway for growth factor-independent survival and repression of BIM. Oncogene 27:7150-7161 2. Balmanno K et al (2009) Intrinsic resistance to the MEK inhibitor AZD6244 (ARRY142886) is associated with weak ERK1/2 signalling and strong PI3K signaling in colorectal tumour cell lines. Int J Cancer 125: 2332-2341 3. Balmanno K & Cook SJ. (2009) Tumour cell survival signalling by the ERK1/2 pathway. Cell Death Diff 16:368-377. 4. Little AS et al (2011) Up-regulation of the driving oncogene, KRAS or BRAF, drives acquired resistance to MEK inhibitors in colorectal cancer cells. Science Signalling. 4 (166) ra17. 5. Little AS et al (2012) Tumour cell responses to MEK1/2 inhibitors – acquired resistance and pathway remodeling. Biochem Soc Trans. 40:73-78 Postdoctoral Research Scientist - Ref. SC-CRUK1-Resist Person Specification Education/Qualifications/Knowledge PhD in biochemistry, cell biology or molecular biology Proven track record of success in publishing results Knowledge of cancer cell biology Experience Experience in good laboratory practice Experience of assaying signal transduction Experience of assaying cell proliferation and apoptosis Experience in RNAi Experience in proteomics or microarrays Essential Essential Desirable Essential Essential Essential Essential Desirable Skills/Abilities Able to comprehend and communicate in the English language to a level appropriate for the position Ability to work independently Good organisational skills Troubleshooting skills Good oral and written communication skills Essential Essential Essential Essential Essential Personal Characteristics Highly motivated researcher Reliability Ability to interact well within a team Keen interest in cancer studies Essential Essential Essential Desirable Special Requirements Able to work in a non-smoking environment Essential The Babraham Institute Postdoctoral Research Scientist – Ref: SC-CRUK1-LTC INFORMATION ON TERMS & BENEFITS The following is for information only and is not contractual statement of terms and conditions. Pay Grade BI 6 Salary £29,557 to £32,840 per annum Working Hours 37 hours per week Holiday Entitlement 25 days p.a. Public Holidays & Privilege Days 10½ days Length of Contract Funding available up to 19 months. Pension Scheme Babraham Institute is able to offer membership of a Group Personal Pension Scheme. You will be auto enrolled into the pension scheme from commencement of employment. Further details will be provided on your first day. The Institute does not make contributions to other personal pension schemes. Restaurant Facilities The Refectory serves hot meals and snacks and the Forum provides a selection of snacks and hot and cold beverages for coffee and tea breaks. Onsite Accommodation The Institute has a number of hostels, flats and houses which can be rented. (There is currently a waiting list for all types of accommodation.) Social Sports & Social Club Nursery Nursery and Holidays Playscheme on site. (Availability of places is dependent on demand.) Car Parking There is free car parking in the Institute Car Park. The Institute is committed to the implementation of a commuting strategy to try and reduce the growth in numbers of cars used to travel to work. Any offer of employment will be subject to security screening and may be subject to health screening. Any offer may also be subject to a general medical.