Redrawing cancer immune transcriptomic maps with Nanopore sequencing

利用纳米孔测序重新绘制癌症免疫转录组图

• 批准号: 2889752
• 金额: --
• 依托单位: University of York
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2889752
• 关键词: Redrawing; cancer; immune; transcriptomic; maps

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

您对癌症免疫学和尖端基因组学/转录组学感兴趣吗？你想在一个由包括免疫学家（拉各斯，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？如果是的话，这对你来说是一个绝佳的机会。您将使用由牛津纳米孔技术（ONT）开发的长读测序平台的显着力量，该项目的iCASE合作伙伴和长读和直接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。这将是一个工具，以改变我们对癌症免疫学的理解，例如通过识别与疾病复发或对治疗的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（ICI）的临床使用已经在肿瘤学中发生了变革，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测序方法由于其在评估替代转录物和3 'UTR使用、poly-A长度和转录后RNA修饰方面的优势，目前处于临床癌症研究的前沿（例如RNA甲基化），所有这些都来自同一次测序运行的单个转录本分辨率。基于正在进行的合作，该项目将在肾癌中应用这种强大的技术（英国每年有超过13，000例新诊断，每年造成超过4，700例死亡）。原发性肾脏肿瘤通过手术切除，然而，20-40%的患者会复发，并接受ICI或受体酪氨酸激酶抑制剂（RTKis）治疗。通过纳米孔测序的应用，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物。在这个项目中，我们将把注意力转向肾脏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靶点。为了实现这一目标，您将使用纳米孔测序来确定体外免疫细胞转录组（例如CD 8 + T细胞耗竭模型）和临床样本。您将接受使用拉各斯组和ONT中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-工业主管团队将帮助您欣赏转化研究的机会，并充分利用将新方法应用于癌症免疫学的机会，并带来切实的机械和临床效益。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，无论您是否已经拥有大数据/生物信息学分析的经验，或者只是有热情和动力来获取它们，我们都希望收到您的来信！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，并以极强的定量技能毕业，并清楚地了解如何将这些应用于推进临床oncology.http://nanoporetech.com