Understanding the consequences of aneuploidy in paediatric cancer

About the Project

Gains and losses of whole chromosomes (aneuploidies) are found in the majority of cancers and clearly influence cancer progression and prognosis. Nevertheless, how aneuploidy, which normally reduces cell fitness, provides a growth advantage for cancer remains paradoxical. In this project, you will use a unique set of cancer cell lines with specifically-engineered aneuploidies, coupled with state-of-the-art genome, proteome, and cell biology techniques, to understand the consequences of aneuploidy in paediatric cancer.

Non-random whole-chromosome aneuploidies are frequent in childhood cancer and, although some are known predictors of outcome, they rarely harbour known gene-specific aberrations that explain carcinogenesis. Understanding the features of gained chromosomes responsible for driving cancer is a key challenge, and it is now clear that cellular context is vital to understand how aneuploidy influences cancer development. Such knowledge should not only aid prognosis and patient treatment stratification, it is also likely to identify new vulnerabilities that can be targeted for the development of new therapies.

We hypothesise that cells with specific chromosome gains in childhood cancer alter DNA methylation, gene and protein expression and thus cell signalling networks to drive cancer, and that the nature of these changes will depend on both (i) the specific chromosome gained and (ii) the cell context. To address this, we have used microcell-mediated transfer to engineer isogenic cell lines containing specific gains of chromosome 7 or chromosome 21 in a variety of acute lymphoblastic leukaemia backgrounds. From these, we have obtained long-read genome, RNA-seq, proteome, 5 phosphoproteome, and drug sensitivity data that will provide an unprecedented comprehensive understanding of aneuploidy-induced changes. Here, you will analyse and build on these data to dissect the consequences of aneuploidy in this important childhood cancer.

The project will involve characterization of the properties of human cell lines by both cell biological and ‘omics methods, providing excellent training in the integration of both bench science and bioinformatics techniques. You will benefit from working in a multidisciplinary team embedded in the leading childhood cancer team in the Newcastle University Centre for Cancer. The supervisory team are committed to supporting your career development, and to promoting an inclusive and positive research culture.

Funding

Students who have, or are expecting to attain, at least an upper second-class honours degree (or equivalent) in a relevant subject, are invited to apply. Funding is available for Home (UK) students to cover tuition fees, a tax-free stipend at the UKRI rate (indicative amount in year 1 in 2026-27, £21,805) and research costs, for four years. Applicants normally required to cover International fees will have to cover the difference between the Home and the International tuition fee rates. There is no additional funding available to cover NHS Immigration Health Surcharge (IHS) costs, visa costs, flights etc.

Funding for this studentship is awarded on a competitive basis and is not guaranteed; availability will depend on the outcome of the selection process and subject to final approval by the University.