Redrawing cancer immune transcriptomic maps with Nanopore sequencing

你对癌症免疫学和前沿基因组学/转录学感兴趣吗？你想在一个由包括免疫学家(拉各斯、库尔策利斯)、临床肿瘤学家(瓦苏德夫)和行业专家(特纳)在内的监督团队支持的环境中攻读博士学位吗？如果是，这对你来说是一个完美的机会。您将使用由牛津纳米孔技术(ONT)开发的长读测序平台的非凡功能，牛津纳米孔技术(ONT)是该项目的iCASE合作伙伴和长读和直接RNA测序的先驱，以探索和重新发现肾癌的免疫基因表达图景。这将是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本。这是本博士将致力于解决的挑战：免疫检查点抑制剂(ICIS)的临床使用在肿瘤学中具有变革性，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，这要归功于它们在评估替代转录本和3‘非编码区使用、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个转录本分辨率上进行的。该项目将在持续合作的基础上，将这项强大的技术应用于肾癌(英国每年有13,000例新诊断，每年导致超过4,700人死亡)。原发性肾肿瘤可以通过手术切除，然而，20%-40%的患者会复发，并接受ICIS或受体酪氨酸激酶抑制剂(RTKis)的治疗。通过纳米孔测序的应用，我们已经发现了数百个与疾病复发相关的新的癌细胞内在转录本。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。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目标。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细胞耗尽模型)和临床样本中的免疫细胞转录本。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-行业指导团队将帮助您欣赏转化性研究中的机会，并从将新方法应用于癌症免疫学中获得最大限度的好处，并带来切实的机制和临床好处。因此，如果您想要使用新技术来探索令人着迷的癌症免疫学世界，无论您已经拥有大数据/生物信息学分析的经验，还是仅仅是想要获得它们的热情和动力，我们都愿意听取您的意见！我们预计，到你博士毕业时，你将在癌症免疫学方面取得重大发现，毕业时将拥有极强的量化技能，并清楚地了解如何将这些技能应用于先进的临床肿瘤学。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