Redrawing cancer immune transcriptomic maps with Nanopore sequencing

Are you interested in cancer immunology and cutting-edge genomics/transcriptomics? Do you want to pursue a PhD in an environment supported by a supervisory team including immunologists (Lagos, Kourtzelis), clinical oncologists (Vasudev), and industry experts (Turner)? 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 pioneers in long-read and direct RNA sequencing, to explore and rediscover immune gene expression landscapes in kidney cancer. This will be a vehicle to transforming our understanding of cancer 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 (e.g. RNA methylation), 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, we will switch our attention to the transcriptomes of immune cells within the kidney tumour microenvironment. This will allow us to discover drivers of disease relapse and novel immunotherapeutic targets.

To achieve this, you will use Nanopore sequencing to determine immune cell transcriptomes in vitro (e.g. models of CD8+ T cell exhaustion) and in clinical samples. 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 cancer immunology, with tangible mechanistic and clinical benefits.

So, if you want to use 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 in cancer immunology and graduate with extremely strong quantitative skills and clear understanding of how these are applied to advance clinical oncology.

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