Population genetic analysis based on the polymorphisms mediated by retrotransposons in the human genomes for cancer risk prediction (RDF25/HLS/APP/SHUKLA)

Cancer is a leading cause of death worldwide, and early detection is crucial for effective treatment. Despite various screening programs, many cancers are not caught early enough when curative treatments can be employed. Liver cancer, in particular, often develops in patients with chronic liver diseases like cirrhosis, but only a small percentage of these patients go on to develop cancer¹. Understanding why some people with chronic liver disease develop cancer while others don't is key to improving early detection and treatment.

Cancer risk depends on several factors including age, genetics, and lifestyle. Identifying individuals at higher risk can be of benefit as closer monitoring can then be performed. Cancer development is a multistep process and the key drivers of cancers arising on a background of chronic liver diseases remain elusive. We have demonstrated the activation and mutagenic consequences of retrotransposons- genetic elements that can "jump" around the genome - in liver cancer^2,3. These elements, when activated, can cause mutations and changes in gene expression⁴ that may influence cancer biology or increase cancer risk. Our studies have also highlighted cancer-relevant gene polymorphism⁵ and germline retrotransposon insertion polymorphisms (RIPs)². Hence, we hypothesise that when activated by the environmental agents associated with chronic liver disease, certain inherited germline retrotransposons predispose individuals to liver cancer development. The identification of RIPs associated with these factors in patients with liver cancer will enable the development of a risk prediction tool.

This project focuses on uncovering the genetic reasons why some people with chronic liver disease develop liver cancer with a specific focus on retrotransposons. We have already performed whole genome sequencing on 900 liver cancer patients and 150 controls. Now, you will help analyse this data to identify retrotransposon insertion polymorphisms (RIPs) that may be linked to cancer risk. A list of potential candidates is already available, which will be updated using in-silico functional prediction tools. By using advanced techniques such as CRISPR-Cas9, we will investigate how these genetic changes affect gene function in cell models and liver tissue samples.

This exciting project could lead to the development of new tools to predict who is at risk of liver cancer, improving screening and early detection. The work could also be expanded to study other types of cancer where retrotransposons play a role⁶.

As a PhD student, you’ll gain hands-on experience with bioinformatics, genome analysis, molecular biology techniques, and cutting-edge technologies like CRISPR. You’ll be involved in every aspect of the project, from data analysis to presenting your findings at conferences, helping you build essential skills for a career in scientific research.

Academic Enquiries

This project is supervised by Ruchi Shukla. For informal academic queries, contact ruchi.shukla@northumbria.ac.uk . For enquiries relating to eligibility or application process, email fc.pgr.admissions@northumbria.ac.uk

Eligibility Requirements:

•       Academic excellence i.e. 2:1 (or equivalent GPA from non-UK universities with preference for 1st class honours); or a Masters (preference for Merit or above); or APEL evidence of substantial practitioner achievement.

•       Appropriate IELTS score, if required.

•       Applicants cannot apply if they are already a PhD holder or if currently engaged in Doctoral study at Northumbria or elsewhere.

•       Must be able to commit to campus-based full-time or part-time study.

To be classed as a Home student, candidates must:

•       Be a UK National (meeting residency requirements), or

•       have settled status, or

•       have pre-settled status (meeting residency requirements), or

•       have indefinite leave to remain or enter.

If a candidate does not meet the criteria above, they would be classed as an International student.  

Applicants will need to be fully enrolled in the UK before stipend payments can commence, and be aware of additional costs that may be incurred, as these are not covered by the studentship, such as:

·        Immigration Health Surcharge

·        If you need to apply for a Student Visa to enter the UK, please refer to https://www.gov.uk/student-visa. Read this information carefully as it is your responsibility to ensure that you hold the funds required for your visa application, otherwise your visa may be refused.

·        Costs associated with English Language requirements (which may be required for students not having completed a first degree in English) will not be paid by the University.

·        International applicants (including EU) must have valid immigration permissions to live and study in the UK if they wish to study on a part-time basis. Northumbria University does not sponsor part-time student visas.

Apply now at https://www.northumbria.ac.uk/research/postgraduate-research-degrees/how-to-apply/   (Select Full-Time PhD or Part-Time PhD depending on your preference)

In your application, include a research proposal of approximately 1,000 words and also the advert reference (e.g. RDF25/…).

Application Deadline: 24 January 2025

Start date of course: 1 October 2025

Northumbria University is committed to creating an inclusive culture where we take pride in, and value, the diversity of our postgraduate research students. We encourage and welcome applications from all members of the community. The University holds a bronze Athena Swan award in recognition of our commitment to advancing gender equality, we are a Disability Confident Leader, a member of the Race Equality Charter and are participating in the Stonewall Diversity Champion Programme. We also hold the HR Excellence in Research award for implementing the concordat supporting the career Development of Researchers and are members of the Euraxess initiative to deliver information and support to professional researchers.