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Elucidating the role of lipid droplets in medulloblastoma tumours


   Department of Life Sciences

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  Dr Maria Niklison Chirou  No more applications being accepted  Funded PhD Project (UK Students Only)

About the Project

The University of Bath is inviting applications for the following funded PhD project commencing as soon as possible (and ideally by January 2023 at the latest).

Overview of the research

Group 3 and Group 4 medulloblastoma (G3/G4-MB), are among the most aggressive and highly metastatic paediatric tumours[1]. These tumours are resistant to surgery, radiotherapy and chemotherapy and sadly most affected children die within three years of diagnosis. The aim of my lab is to identify novel metabolic vulnerabilities of G3/G4-MB to enable us to find new therapeutic targets.

Metabolic adaptation processes are believed to provide cancer cells with proliferation and survival benefits over normal cells[2]. However, these processes can also make tumour cells selectively “addicted” to certain nutrients, offering an attractive therapeutic target. The most prominent metabolic adaptation in tumours is an increase in glucose uptake and the use of aerobic glycolysis. But other metabolic processes are also enhanced as part of tumour metabolic reprogramming[3].

Lipid metabolism plays a key role in cancer development and metastasis. Lipids are essential for membranes morphology and formation, energy storage, production of signalling molecules, and also as an important energy source to generate ATP[4]. Importantly, we know very little about the mechanisms by which cancer cells produced lipid droplet, cytosolic fat storage organelles present in most cells.

Increased lipid metabolism has been reported in medulloblastoma[5]. Our exciting preliminary data demonstrates that G3/G4-MB cells have increased lipid metabolism with enhanced deposit of lipid droplets. Importantly, treatment with lipid pathway inhibitors reduced cell migration and proliferation in primary G3/G4-MB cells.

The aim of this project is to elucidate the role of lipid droplets in aggressive MB, particularly the mechanism by which lipid droplets support metastasis of G3/G4-MB, with the final goal to understand if anti-lipid pathway drugs could be developed as novel therapeutic targets for these tumours.

This studentship will combine state-of-the-art quantitative cell imaging and advanced cell culture techniques. She/he will learn how to growth medulloblastoma cells and tumour organoids. She/he will also learn how to work with xenograft mouse model. The student will also be trained in other cutting-edge molecular biology techniques to study gene expression, protein-DNA interactions and protein-protein interactions.

Project keywords: Lipid droplets, medulloblastoma, paediatric tumours, metastasis, lipid metabolism. 

Candidate Requirements:

Applicants should hold, or expect to receive, a First Class or good Upper Second Class Honours degree (or the equivalent). A master’s level qualification would also be advantageous.

Non-UK applicants must meet our English language entry requirement.

Enquiries and Applications:

Informal enquiries are welcomed and should be directed to Dr Maria Niklison Chirou, email address [Email Address Removed].

Formal applications should be made via the University of Bath’s online application form for a PhD in Pharmacy & Pharmacology.

More information about applying for a PhD at Bath may be found on our website.

Note: Applications may close earlier than the advertised deadline if a suitable candidate is found. We advise you to contact Dr Niklison Chirou for an informal discussion prior to applying and to submit your formal application as early as possible.

Funding Eligibility:

To be eligible for funding, you must qualify as a Home student. The eligibility criteria for Home fee status are detailed and too complex to be summarised here in full; however, as a general guide, the following applicants will normally qualify subject to meeting residency requirements: UK and Irish nationals (living in the UK or EEA/Switzerland), those with Indefinite Leave to Remain and EU nationals with pre-settled or settled status in the UK under the EU Settlement Scheme. This is not intended to be an exhaustive list. Additional information may be found on our fee status guidance webpage, on the GOV.UK website and on the UKCISA website.

Equality, Diversity and Inclusion:

We value a diverse research environment and aim to be an inclusive university, where difference is celebrated and respected. We welcome and encourage applications from under-represented groups.

If you have circumstances that you feel we should be aware of that have affected your educational attainment, then please feel free to tell us about it in your application form. The best way to do this is a short paragraph at the end of your personal statement.


Funding Notes

A studentship includes Home tuition fees and a stipend (£16,062 per annum, 2022/23 rate) for up to 3.5 years. The successful student will also have access to funds for consumables and other research expenses. Eligibility criteria apply – see Funding Eligibility section above.

References

1- Northcott, P.A., et al., Medulloblastomics: the end of the beginning. Nat Rev Cancer, 2012. 12(12): p. 818-34.
2- Dang, C.V., Links between metabolism and cancer. Genes Dev, 2012. 26(9): p. 877-90.
3- Baenke, F., et al., Hooked on fat: the role of lipid synthesis in cancer metabolism and tumour development. Dis Model Mech, 2013. 6(6): p. 1353-63.
4- Luo X et al. Emerging roles of lipid metabolism in cancer metastasis. Molecular Cancer (2017) 16:76.
5- Tech K et al. Energy metabolism in neurodevelopment and medulloblastoma. Transl Pediatr, 2015. 4(1): 12–19.
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