Identifying metabolic perturbations that drive kidney cancer

Description

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal malignancies and is associated with poor survival. ccRCC is driven by the loss of the VHL gene, which results in the constitutive activation of signalling mediated by the hypoxia-inducible factors (HIFs). ccRCC often displays a complex metabolic reprogramming affecting glucose, glycogen, cholesterol, amino acid and glutathione metabolism.

It remains unclear what drives the abnormal cellular metabolism in ccRCC and what are the consequences of these changes on the molecular mechanisms that promote proliferation and carcinogenesis. As a way to find novel treatments, this project wants to understand how this metabolic rewiring leads to alterations in intracellular redox balance and explore cancer cell vulnerabilities.

This interdisciplinary project aims to systematically evaluate the pro-tumorigenic role of metabolic genes and identify metabolic vulnerabilities in renal cancer linked to redox imbalances, using novel highly-localised genetically-encoded redox biosensors.

To understand how metabolic processes drive endogenous redox properties, the project will utilise CRISPR screen libraries targeting metabolic genes, in normal and cancer cells. The expression of metabolic genes will be modulated and the effect that has on intracellular redox balance will be monitored using flow cytometry. The data generated will expand our understanding of metabolic differences between normal and cancer cells and will indicate potential genes, that when absent or upregulated, can promote cell death only in cancer cells but not normal cells. As these changes might occur directly or indirectly, this project will subsequently pinpoints the exact mechanisms that drive these differences.

The Kritsiligkou lab (www.kritsiligkou.com) is part of the Department of Biochemistry, Cell and Systems Biology. The Sciacovelli lab is part of the Department of Molecular and Clinical Cancer Medicine. There is excellent access to core facilities and great support for the development of researchers in a vibrant and dynamic international environment.

The application process is a two-step processes. Firstly, an application should be made with a full CV, transcripts and motivational letter, send to Dr Kritsiligkou (pari@liverpool.ac.uk). When a candidate has been selected following interview, a formal online application will be required. Deadline for applications is 31st July 2025. Applications will close earlier if a suitable candidate has been identified.

Requirements: A minimum of 2.1 degree is required in Cancer Biology, Biochemistry, Chemistry, Biological Sciences or related subjects and evidence of lab experience. Proof of English language knowledge requirements: IELTS minimum overall 8 with no component below 7. TOEFL iBT a minimum of 100/120