Single Cell-Level Functional Proteomics and Genomics exemplified in Cancer and Immunology

癌症和免疫学中的单细胞水平功能蛋白质组学和基因组学实例

• 批准号: MR/M022927/1
• 负责人: Mark Peakman
• 金额: $ 304.11万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FM022927%2F1
• 关键词: Single; Cell; Level; Functional; Proteomics

We propose to create a state-of-the-art facility for studying the function and nature of single human cells involved in disease processes, combining the latest developments in cell isolation and analysis of genes and proteins. The system will be developed in collaboration with industrial partners, and exemplified via cohesive research programmes in immune-mediated disease, regenerative medicine and cancer. These provide distinct challenges but have significant cross-talk, making them ideal for exploring the full potential of the facility. For example, cancer growth and spread are characterised by variants of cells from "self" developing ways of evading the immune system; whilst autoimmune and inflammatory disease (diabetes, arthritis) arises because the immune system targets self. Moreover, in transplantation and regenerative medicine, responses to self and neo-self cells are a major barrier to graft acceptance. Through the synergistic development of new technology platforms that analyse complex cellular processes in cancer, inflammation, autoimmunity and transplantation on a single site that houses all of the relevant expertise and related infrastructure already, we aim to resolve complex disease processes at the single cell level. The expertise and methodologies brought together by the consortium create an opportunity to share technological benefits in an overlapping set of systems. Our goal is that the Single Cell-Level Functional Proteomics and Genomics system, once developed, will accelerate clinically important discoveries about disease processes, their treatment and monitoring, and act as a model for the establishment of similar facilities in centres of excellence across a range of clinical arenas.

我们建议创建一个最先进的设施，结合细胞分离和基因和蛋白质分析的最新发展，研究参与疾病过程的单个人类细胞的功能和性质。该系统将与工业合作伙伴合作开发，并通过在免疫介导性疾病、再生医学和癌症方面的协调研究计划加以示范。这些都带来了不同的挑战，但具有显著的串扰，使它们成为探索设施全部潜力的理想选择。例如，癌症的生长和扩散的特点是“自身”的细胞变异，形成逃避免疫系统的方式；而自身免疫和炎症性疾病(糖尿病、关节炎)的出现是因为免疫系统以自身为目标。此外，在移植和再生医学中，对自我和新自我细胞的反应是移植接受的主要障碍。通过协同开发新的技术平台，在一个已经拥有所有相关专业知识和相关基础设施的单一网站上分析癌症、炎症、自身免疫和移植中的复杂细胞过程，我们的目标是在单细胞水平上解决复杂的疾病过程。该联盟带来的专门知识和方法创造了在一套相互重叠的系统中分享技术利益的机会。我们的目标是，一旦开发出单细胞级功能蛋白质组学和基因组学系统，将加快关于疾病过程、治疗和监测的临床重要发现，并成为在一系列临床领域的卓越中心建立类似设施的典范。

项目成果

Spatiotemporal segregation of human marginal zone and memory B cell populations in lymphoid tissue.

• DOI: 10.1038/s41467-018-06089-1
• 发表时间: 2018-09-21
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Zhao Y;Uduman M;Siu JHY;Tull TJ;Sanderson JD;Wu YB;Zhou JQ;Petrov N;Ellis R;Todd K;Chavele KM;Guesdon W;Vossenkamper A;Jassem W;D'Cruz DP;Fear DJ;John S;Scheel-Toellner D;Hopkins C;Moreno E;Woodman NL;Ciccarelli F;Heck S;Kleinstein SH;Bemark M;Spencer J
• 通讯作者: Spencer J

Semi-autonomous real-time programmable fluorescence lifetime segmentation with a digital micromirror device.

• DOI: 10.1364/oe.26.031055
• 发表时间: 2018-11
• 期刊: Optics express
• 影响因子: 3.8
• 作者: J. Aluko;Camille Perrin;V. Devauges;J. Nedbal;S. Poland;D. Matthews;J. Whittaker;S. Ameer-Beg