PhD studentship: Hexokinase 2 promotes brain tumour meningioma growth by metabolic rewiring

Applications are invited for a three-year PhD studentship. The studentship should start on 1 Oct 2022 but 1 April 2022 is possible.

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To apply please use the online application form. Simply search for PhD Medical Studies, then clearly state that you are applying for a PhD studentship and name the project at the top of your personal statement.

Online application

Before applying, please ensure you have read the Doctoral College’s general information on applying for a research degree.

For more information on the admissions process, please contact doctoralcollege@plymouth.ac.uk.

DoS Oliver Hanemann

2nd Supervisor Leandro José de Assis

3rd Supervisor Jane Carré


Project Description

The most common primary brain tumours are meningiomas, the analysis of hexokinase 2 (HK2) on grades II and III shows higher levels of HK2 compared to normal human meningeal tissue and meningioma grade I. [1] Tumour tissues due to uncontrolled growth rate overexpress HK2 and it is preferentially localised in the mitochondria interacting with proteins and controlling cell survival and masking cancer cells due to reduced interferon production that plays a role in cancer immune surveillance. [2,3] Thus, understanding how HK2 controls cancer development allows us to identify potential targets for drug intervention and cancer control. Our preliminary data showed meningioma presents higher levels of HK2. Indeed, HK2 showed higher expression in higher grade samples, II and III.

This PhD sits in the Brain Tumour Centre of Excellence with about 25 researchers working in state of the art facilities. The project aims to characterise the role of HK2 on meningioma and to understand the effect on meningioma development after HK2 depletion. This project proposes to understand the mechanistic regulation of HK2 on cancer metabolism identifying possible targets for drug development and cancer treatment. Training will be provided for the development of both knowledge and technical skills to enable the trainee to conduct high-quality and independent research. 

References:

1. Dunn, J. et al., Proteomic analysis discovers the differential expression of novel proteins and phosphoproteins in meningioma including NEK9, HK2 and SET and deregulation of RNA metabolism. EBioMedicine 40, 77–91 (2019).

2. Zhang, W. et al., Lactate Is a Natural Suppressor of RLR Signaling by Targeting MAVS. Cell 178, 176–189.e15 (2019).

3. Ciscato, F. et al., Hexokinase 2 displacement from mitochondria‐associated membranes prompts Ca 2+ ‐dependent death of cancer cells. EMBO Rep. 21, 1–13 (2020).

 

Eligibility

Applicants should have (at least) a first or upper second-class honours degree in an appropriate subject and preferably a relevant MSc or MRes qualification.

The studentship is supported for three years and includes full home tuition fees plus a stipend of £15,609 per annum (2021/22 rate, uplift will apply for 2022/23). The studentship will only fully fund those applicants who are eligible for home fees with relevant qualifications. Applicants normally required to cover overseas fees will have to cover the difference between the home and the overseas tuition fee rates (approximately £12,670 per annum for 2022/23).

If you wish to discuss this project further informally, please contact Professor C Oliver Hanemann at Oliver.Hanemann@plymouth.ac.uk.


For more information on the admissions process in general, please contact doctoralcollege@plymouth.ac.uk.

The closing date for applications is 12 noon on 18 February 2022. Shortlisted candidates will be invited for interview later in June. We regret that we may not be able to respond to all applications. Applicants who have not received an offer of a place should consider their application has been unsuccessful on this occasion.