Redrawing cancer immune transcriptomic maps with Nanopore sequencing

你对癌症免疫学和前沿基因组学/转录组学感兴趣吗？你想在一个由包括免疫学家（Lagos, Kourtzelis），临床肿瘤学家（Vasudev）和行业专家（Turner）在内的监督团队支持的环境中攻读博士学位吗？如果是，这对你来说是个绝佳的机会。您将使用牛津纳米孔技术公司（ONT）开发的长读测序平台的强大功能，该公司是该项目的iCASE合作伙伴，也是长读和直接RNA测序的先驱，探索和重新发现肾癌中的免疫基因表达景观。这将成为改变我们对癌症免疫学理解的载体，例如通过识别与疾病复发或治疗反应相关的免疫转录物。免疫检查点抑制剂（ICIs）的临床应用已经在肿瘤学领域发生了变革，但仍然存在重大挑战，包括大量患者缺乏反应。长读和直接RNA测序方法目前处于临床癌症研究的前沿，这得益于它们在评估替代转录物和3'UTR使用、poly-A长度和转录后RNA修饰（例如RNA甲基化）方面的优势，所有这些都是在同一测序运行的单转录物分辨率下进行的。在持续合作的基础上，该项目将把这项强大的技术应用于肾癌（英国每年有13000例新诊断，导致4700多人死亡）。原发性肾肿瘤通过手术切除，然而，20-40%的患者复发，并接受ICIs或受体酪氨酸激酶抑制剂（RTKis）治疗。通过应用纳米孔测序，我们已经发现了数百种与疾病复发相关的新型癌细胞内在转录本。在这个项目中，我们将把注意力转向肾肿瘤微环境中免疫细胞的转录组。这将使我们能够发现疾病复发的驱动因素和新的免疫治疗靶点。为了实现这一目标，您将使用纳米孔测序来确定体外（例如CD8+ T细胞衰竭模型）和临床样品中的免疫细胞转录组。您将接受使用拉各斯小组和ONT已经使用的协议和生物信息学管道获取和分析纳米孔测序数据的培训。学术-临床-工业导师团队将帮助您欣赏转化研究的机会，并最大限度地将新方法应用于癌症免疫学，具有切实的机制和临床效益。因此，如果您想使用新技术来深入研究癌症免疫学的迷人世界，无论您是否已经有大数据/生物信息学分析的经验，还是只是对获得它们的热情和动力，我们都希望听到您的声音！我们预计，到博士学位结束时，您将在癌症免疫学方面取得重大发现，毕业时具有极强的定量技能，并清楚地了解如何将这些技能应用于推进临床肿瘤学。http://nanoporetech.com

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.http://nanoporetech.com