The Oxford Single Cell Biology Consortium

我们研究单个细胞生物学的能力的局限性历来是一个主要障碍，它抑制了我们对生物医学研究中一些基本问题的理解，如癌症的发病、“自我”的免疫学决定以及纯化组织特异性干细胞的能力。单细胞基因组学领域的最新发展为揭示这种复杂组织中的单个细胞差异提供了前所未有的机会。拟议研究的目标是在牛津建立一个单细胞生物学中心（CSCB），该中心将利用这一开创性技术，以改进各种人类疾病的诊断、分层和治疗。CSCB将由Weatherall分子医学研究所（WIMM）协调，该研究所在单细胞研究方面具有长期的技术和战略专长。这笔资金将用于加强校园内多个关键领域的单细胞研究能力：数据分析：单细胞基因组学研究产生了大量数据，随之而来的是对这些复杂数据集的分析和正确解释的挑战。我们建议建立一个全新的研究小组，致力于开发单细胞生物学数据的统计和计算分析的新方法，并将其应用于医学。这个小组将设在WIMM即将开发的新空间，但由校园内的顶尖科学家共同领导。这项新计划将为整合牛津大学校园内单细胞生物学研究的多学科、科学和技术创新提供一条清晰的途径，并为英国医学提供这种方法的突破性应用。最先进的设施：我们将开发单细胞生物学研究实验室，让研究小组在校园内进行这些研究。这些设施将容纳尖端的技术平台，重要的是，将为进行单细胞实验创造“超清洁”的环境。这是必要的，因为非常低水平的背景“污染”使得单细胞实验的解释具有挑战性。项目：作为如何应用这项技术解决人类疾病的基本问题的一个具体例子，CSCB的主要研究方案将侧重于红细胞的遗传性疾病。这些疾病是全世界最常见的人类遗传疾病之一，估计每年有30万受影响的婴儿出生，英国受影响的患者总数约为16,000人。目前，受严重影响的个体接受支持性治疗，包括终身输血和治疗，以防止铁在体内的积累，这是昂贵的，负担沉重的，并引起严重的长期临床并发症。在这里，我们建议对患者自身血液干细胞中的受损基因进行“基因修复”。单细胞生物学将是该项目的核心：首先，单细胞基因组方法将用于识别血液干细胞，这是该疗法的最佳靶点。其次，单细胞分析将用于评估这种方法的安全性和有效性。这一方案的重点是发展一种治疗血红蛋白病的全新方法，有可能改变可通过干细胞移植治愈的所有人类遗传疾病的治疗方法。这是校园内许多正在开发的项目中的一个例子，这些项目将通过改进单细胞研究能力的发展而大大促进。牛津大学在单细胞生物学这一新兴领域处于世界领先地位，并将这些技术应用于大学内外的重要临床和基础生物学问题。

Limitations in our ability to study the biology of individual cells has historically been a major obstacle, inhibiting our understanding of some fundamental problems in biomedical research such as the onset of cancer, the immunological determination of 'self', and the ability to purify tissue-specific stem cells. Recent developments in the field of single cell genomics is now opening up unprecedented opportunities to uncover individual cell differences within such complex tissues. The objective of the proposed research is to establish a Centre of Single Cell Biology (CSCB) in Oxford that will take advantage of this pioneering technology in order to improve the diagnosis, stratification and treatment of a wide variety of human diseases. The CSCB will be coordinated by the Weatherall Institute of Molecular Medicine (WIMM) which has a long-standing technical and strategic expertise in single cell research. The capital development will be used to enhance single-cell research capabilities across the campus in a number of key areas:Data analysis: Single cell genomics studies generate an enormous amount of data, with consequent challenges for the analysis and correct interpretation of these complex data sets. We propose to establish an entirely new research group devoted to the development of novel approaches for the statistical and computational analysis of single cell biology data and its application to medicine. This group will be located in new space to be developed at the WIMM, but jointly led by leading scientists across the campus. This new initiative will provide a clear pathway to integrate multidisciplinary, scientific and technical innovation in single cell biology research across the Oxford University Campus and to provide ground-breaking applications of this approach to medicine in the UK.State of the art facilities: We will develop single cell biology research laboratories to allow practical access for research groups conducting these studies across the campus. These facilities will house cutting edge technology platforms and, importantly, will create "ultra clean" environments to carry out single cell experiments. This is necessary as very low levels of background "contamination" make the interpretation of single cell experiments challenging. Projects: As a specific example of how this technology will be applied to address fundamental problems in human disease, the lead programme of research in the CSCB will be focused on inherited disorders of red blood cells. These disorders are amongst the most common of all human genetic diseases worldwide with an estimated 300,000 affected babies born each year and a total number of affected UK patients of ~16,000. Currently, severely affected individuals are treated with supportive care, including lifelong blood transfusion and treatment to prevent accumulation of iron in the body, which is costly, burdensome, and gives rise to serious, long-term clinical complications. Here we propose to "genetically repair" the damaged genes in the patient's own blood stem cells. Single cell biology will be central to this project: First, single cell genomic approaches will be used to identify the blood stem cells which are the best target for this therapy. Second, single-cell analysis will be used to assess the safety and efficiency of this approach. This programme, focussed on developing an entirely new approach to treating the haemoglobinopathies, has the potential to transform the treatment of all human genetic diseases that can be cured by stem cell transplantation. This is one example of many projects in development across the campus which will be greatly facilitated by the development of improved single cell research capabilities.Oxford is in a very strong position to take a world-leading role in the up-and-coming area of Single Cell Biology and application of these technologies to important clinical and basic biology questions across the University and beyond.