"Stemamers": evaluation of slow off-rate aptamers (Somamers) in stem cell biotechnology.

“Stemamers”：干细胞生物技术中慢解离速率适体（Somamers）的评估。

• 批准号: 1946868
• 金额: --
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1946868
• 关键词: Stemamers; evaluation; slow; off; rate

Induced pluripotent stem cells have unprecedented biotechnological potential, from providing physiological models for the identification of pharmaceutical leads to the production of defined tissues for cell therapy. A key barrier to the large scale industrial exploitation of these potentials stems from the two-dimensional, demanding culture format and the cost and irreproducibility of the biological additives to culture media. These challenges could be addressed by the modulation of stem cell behaviour in vitro by ligation of their cell-surface receptors by high-affinity nucleic acid ligands. SomaLogic has developed such aptamers using their proprietary SOMAmer technology, and this project will build on a research collaboration framework agreement recently concluded between them and Oxford to evaluate their potential. The student would benefit from the support of two other collaborative projects currently underway between the two groups. Depending on progress, the student would have the opportunity to evaluate Somamers against other cell surface molecules involved in stem cell maintenance and differentiation. Importantly, the student would also use the unique SOMAmer reagents to explore the biology adherens junctions in the physiology of stem cells. Using a combination of confocal microscopy and proteomic techniques in use in the James Lab, they would explore the kinetics of the formation of adherens junctions in both primed and naïve pluripotent stem cells, and the effect of their disruption by Somamers to e-Cadherin on down-stream signalling pathways. The results would not only shed critical light on the maintenance of the pluripotent states, but also offer further avenues for biotechnological manipulation.Principal Location: Sir William Dunn School of Pathology, University of OxfordNon-academic partner location: SomaLogic is located in a well-designed facility in Boulder, Colorado and has about 170 employees. The facility has approximately 20,000 square feet of laboratory space, separated into two buildings for technology development, aptamer screening, assay development and assay execution, and chemistry. Training in the latest methods of nucleic acid chemistry and biotechnology, including the use of aptamers in high-sensitivity proteome detection arrays will be provided during the residency at SomaLogic.This project is supported through the Oxford Interdisciplinary Bioscience Doctoral Training Partnership (DTP) BBSRC Industrial CASE (iCASE) studentship programme. The student recruited to this project will join a cohort of students enrolled in the DTP's interdisciplinary training programme, and will be able to take full advantage of the training and networking opportunities available through the DTP.

诱导多能干细胞具有前所未有的生物技术潜力，从提供用于鉴定药物的生理模型到产生用于细胞治疗的特定组织。大规模工业化开发这些潜力的一个关键障碍来自于二维的、要求很高的培养形式以及生物添加剂在培养基中的成本和不可重复性。这些挑战可以通过通过高亲和力的核酸配体连接干细胞表面受体来调节干细胞的体外行为来解决。SomaLogic使用他们专有的SOMAmer技术开发了这种适配子，该项目将建立在他们与牛津大学最近达成的研究合作框架协议的基础上，以评估他们的潜力。这名学生将受益于两个小组目前正在进行的另外两个合作项目的支持。根据进展情况，学生将有机会针对参与干细胞维持和分化的其他细胞表面分子评估SOMAmers。重要的是，学生还将使用独特的SOMAmer试剂来探索干细胞生理学中的生物黏附连接。利用詹姆斯实验室中使用的共聚焦显微镜和蛋白质组学技术的组合，他们将探索在启动和幼稚的多能干细胞中形成黏附连接的动力学，以及它们被SOMAmers破坏对e-钙粘附素下游信号通路的影响。这一结果不仅将为维持多能性状态提供关键信息，还将为生物技术操作提供进一步的途径。主要地点：牛津大学威廉·邓恩爵士病理学院非学术合作伙伴地点：SomaLogic位于科罗拉多州博尔德市一家设计良好的设施中，拥有约170名员工。该设施有大约20,000平方英尺的实验室空间，分为两栋建筑，用于技术开发、适体筛选、分析开发和分析执行以及化学。在SomaLogic实习期间，将提供关于核酸化学和生物技术最新方法的培训，包括在高灵敏度蛋白质组检测阵列中使用适体。该项目由牛津跨学科生物科学博士培训伙伴关系(DTP)BBSRC工业案例(ICASE)学生方案支持。被招募到这个项目的学生将加入DTP跨学科培训方案的学生队列，并将能够充分利用DTP提供的培训和联网机会。