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3-year PhD Studentship (Fixed Term)

University of Cambridge - Department of Pathology

Qualification Type: PhD
Location: Cambridge, Hybrid
Funding for: UK Students, EU Students, International Students
Funding amount: See advert for details
Hours: Full Time
Placed On: 23rd February 2024
Closes: 5th March 2024
Reference: PK40360

Applications are invited for a fully-funded 3-year studentship based in the Department of Pathology at the University of Cambridge under the supervision of Prof Nicholas Coleman and Dr Anton Enright.

Project title: Investigating Alternative Splicing As A Driver Mechanism And Therapeutic Target In Squamous Cell Carcinoma

Squamous cell carcinomas (SCCs) are common malignancies that arise at sites including the skin, aerodigestive tract and genitourinary tract. Despite different SCCs being associated with at least one carcinogenic insult (e.g. tobacco, human papillomavirus infection and UV damage), the drivers of SCC carcinogenesis remain largely elusive. Our lab is testing the hypothesis that aberrant RNA splicing is a central mechanism of carcinogenesis in SCCs. We have recently shown that splicing dysregulation in SCCs is not a passenger phenomenon, but likely constitutes a critical driver of oncogenesis, reflected by splicing aberrations in hallmark- related genes across SCC subtypes and a difference in splicing regulation compared with healthy tissues and other tumour types.

This studentship will allow us to advance our understanding of how splicing contributes to oncogenesis in SCC and whether it is a vulnerability that can be targeted therapeutically.

Our objectives will be:

  1. Build an atlas of alternative splicing in SCC, using, single-cell RNA sequencing, bulk deep transcriptional profiling and bulk whole genome sequencing. All data will be processed using our bespoke splice-aware RNA-Seq pipelines. The datasets will be examined to characterize subtype-specific and cross-subtype splicing signatures, as well as signatures linked to known causative environmental factors, such as UV damage or human papillomavirus infection.

  2. Understand the co-evolution of aberrant splicing and progression of HPV16-associated SCC, using the unique cell line model W12.

  3. Characterise the role of the splicing factor serine/arginine-rich splicing factor 10 (SRSF10) in regulating oncogenic splicing in SCC, by tracking splicing changes following depletion of SRSF10 in SCC vs. adenocarcinoma and non-malignant cell lines.

This is a three year PhD studentship, funded by The Pathological Society of Great Britain and Ireland.

It involves a combination of computational and wet lab research.

Applicants should hold (or expect to obtain) the equivalent of a UK 2.1 or higher in an undergraduate honours or Masters degree in a relevant subject such as molecular biology, genetics or computational biology. The studentship is open to those eligible for the Home rate of University fees.

Applications should include academic transcripts, CV, statement of purpose and two references.

Applications are welcome from internal candidates who would like to apply for the role on the basis of a secondment from their current role in the University.

If you have any queries regarding the application process please contact postgrad@path.cam.ac.uk

Please quote reference PK40360 on your application and in any correspondence about this vacancy.

The University actively supports equality, diversity and inclusion and encourages applications from all sections of society.

The University has a responsibility to ensure that all employees are eligible to live and work in the UK.

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