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Regulation of cancer cell metabolism by mechanical tissue cues

  • Full or part time
  • Application Deadline
    Saturday, February 15, 2020
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

Stipend: £18,000 (inclusive of London allowance) per annum + Tuition Fees (Home/EU rate) for 3 years. A consumables budget is also provided.

Fully-funded PhD position in Cancer Biology and Biomechanics at Imperial College London. The Cancer Cell Protein Metabolism group in the Department of Immunology and Inflammation at Imperial College London (led by Holger Auner) is looking for a PhD candidate who is keen to investigate the interplay between tissue mechanics and metabolic rewiring in multiple myeloma, a common B cell malignancy. The group is largely funded by Cancer Research UK grants and is using state-of-the-art integrative approaches (‘omics’) to understand how the ubiquitin-proteasome system governs cellular metabolism to reveal druggable cancer cell vulnerabilities. They are part of the newly established Hugh and Josseline Langmuir Centre for Myeloma Research at Imperial College London, where a growing number of clinical researcher and basic scientists work on several aspects of myeloma biology.

You will also work closely with Eileen Gentleman’s lab at King’s College London whose research focuses on developing biomaterials to modulate the biophysical properties of the 3D cell niche to control cell fate for tissue engineering. The Gentleman lab have developed synthetic hydrogels that mimic many tissue properties and provide an excellent model to understand the role of 3D physical properties in regulating cellular behaviours.

Your PhD studies will define how mechanical tissue characteristics regulate key aspects of myeloma cell metabolism. Your findings will also support the development of in vitro tools that integrate mechanical and metabolic features of the tumour microenvironment for predicting drug sensitivity. The work may be best suited for a cancer cell biologist who is happy to engage with biomechanical approaches but candidates with a bioengineering background are also encouraged to apply.

Applicants are requested to send a full CV (including the names and email addresses of two academic referees), and personal statement detailing why you are interested in the research project (maximum 1 side A4, font size 12 Arial) to Jonathan Shepherd (). Suitable candidates will be asked to complete an electronic application form at Imperial College London in order for their qualifications to be addressed by College Registry.

Candidates are encouraged to contact Holger Auner () to discuss their application.

Funding Notes

The position, fully funded by Imperial’s Department of Immunology and Inflammation, is open to UK and EU nationals (recent or current residency in the UK is not a prerequisite). Applicants must have or expect to gain a First or Upper Second class undergraduate degree in the relevant subject. A Masters Degree is desirable but not essential.

A tax-free stipend and home UK/EU fees for 3 years will be awarded. Overseas students should be able to demonstrate adequate financial support to cover the difference between the home/EU and the overseas fee. Applicants must meet Imperial College’s English language requirements: View Website

References

The coordinated action of VCP/p97 and GCN2 regulates cancer cell metabolism and proteostasis during nutrient limitation. Parzych K, Saavedra-García P, Valbuena GN, Al-Sadah HA, Robinson ME, Penfold L, Kuzeva DM, Ruiz-Tellez A, Loaiza S, Holzmann V, Caputo V, Johnson DC, Kaiser MF, Karadimitris A, Lam EW, Chevet E, Feldhahn N, Keun HC, Auner HW. Oncogene 2019;38(17):3216-3231. doi: 10.1038/s41388-018-0651-z.

Bi-directional cell-pericellular matrix interactions direct stem cell fate. Ferreira SA, Motwani MS, Faull PA, Seymour AJ, Yu TTL, Enayati M, Taheem DK, Salzlechner C, Haghighi T, Kania EM, Oommen OP, Ahmed T, Loaiza S, Parzych K, Dazzi F, Varghese OP, Festy F, Grigoriadis AE, Auner HW, Snijders AP, Bozec L, Gentleman E. Nature Communications 2018;9(1):4049. doi: 10.1038/s41467-018-06183-4.

An engineered, quantifiable in vitro model for analysing the effect of proteostasis-targeting drugs on tissue physical properties. Loaiza S, Ferreira SA, Chinn TM, Kirby A, Tsolaki E, Dondi C, Parzych K, Strange AP, Bozec L, Bertazzo S, Hedegaard MAB, Gentleman E, Auner HW. Biomaterials 2018 Nov;183:102-113. doi: 10.1016/j.biomaterials.2018.08.041.

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