Exploring cancer transcriptomes with Nanopore long-read sequencing


   MRC DiMeN Doctoral Training Partnership

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  Prof D Lagos, Dr N Vasudev, Dr David Stoddart  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Are you interested in cancer gene expression, immunology, and cutting-edge genomics/transcriptomics? Do you want to pursue a PhD in an environment supported by a supervisory team including immunologists and RNA biologists (Lagos, Kourtzelis), clinical oncologists (Vasudev), and leading industry experts (Oxford Nanopore Technologies)? If yes, this is the perfect opportunity for you.

You will use the remarkable power of the long-read sequencing platforms developed by Oxford Nanopore Technologies (ONT), the project’s iCASE partner and global leaders in long-read and direct RNA sequencing, to explore and explore gene expression landscapes in kidney cancer. This will be a vehicle to transforming our understanding of cancer biology and  immunology, for example through identifying immune transcripts associated with disease relapse or response to treatment.

Here is the challenge this PhD will aim to address: The clinical use of immune checkpoint inhibitors (ICIs) has been transformative in oncology, but significant challenges remain, including lack of response by a substantial number of patients. Long-read and direct RNA sequencing methodologies are currently at the cutting-edge of clinical cancer research thanks to their superiority in assessing alternative transcript and 3’UTR usage, poly-A length and post-transcriptional RNA modifications, all at single transcript resolution from the same sequencing run.

Building on an ongoing collaboration, this project will apply this powerful technology in kidney cancer (>13,000 new diagnoses/year in the UK causing more than 4,700 deaths/year). Primary kidney tumours are surgically removed, however, 20-40% of patients experience relapse and are treated with either ICIs or receptor tyrosine kinase inhibitors (RTKis). Through application of Nanopore Sequencing, we have already discovered hundreds of novel cancer cell-intrinsic transcripts associated with disease relapse. In this project, you will combine this information with insight into the transcriptomes of immune cells within the kidney tumour microenvironment. You will spearhead innovative method development and applications, such as targeted direct RNA sequencing. This will allow you to discover drivers of disease progression and response to treatment, which can be the next generation immunotherapeutic targets.

To achieve this, you will be trained in both obtaining and analysing Nanopore sequencing data using protocols and bioinformatics pipelines already used in the Lagos group and ONT. The academic-clinical-industrial supervisor team will help you appreciate opportunities in translational research and make the most from applying novel methodologies to oncology, with tangible mechanistic and clinical benefits.

So, if you want to use ground-breaking new technologies to delve into the fascinating world of cancer immunology, and whether you already have experience with big data/bioinformatics analysis or just the enthusiasm and drive to acquire them, we would like to hear from you! We anticipate that by the end of your PhD you will have made significant discoveries and graduate with extremely strong quantitative skills and clear understanding of how these are applied to advance clinical oncology.

Benefits of being in the DiMeN DTP:

This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle, York and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.

We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.

Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: https://www.dimen.org.uk/blog 

Further information on the programme and how to apply can be found on our website:

https://www.dimen.org.uk/how-to-apply 


Biological Sciences (4)

Funding Notes

iCASE Award: Industrial partnership project
Fully funded by the MRC for 4yrs, including a minimum of 3 months working with an industry partner.

Funding will cover tuition fees and an enhanced stipend (£21,122 for 2023/2024). We also aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of full studentships to international applicants. Please read additional guidance here: https://www.dimen.org.uk/eligibility-criteria
Studentships commence: 1st October 2024

References

Long-read RNA sequencing redefines the clear cell renal cell carcinoma transcriptome and reveals novel genes and transcripts associated with disease recurrence and immune evasion
https://www.medrxiv.org/content/10.1101/2023.09.08.23295204v1.full
Checkpoint inhibitor immunotherapy in kidney cancer
https://www.nature.com/articles/s41585-020-0282-3
http://nanoporetech.com

Where will I study?