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

诱导多能干细胞具有前所未有的生物技术潜力，从为药物鉴定提供生理模型到生产用于细胞治疗的特定组织。对这些潜力进行大规模工业开发的一个关键障碍来自于二维的、要求很高的培养形式，以及培养基中生物添加剂的成本和不可复制性。这些挑战可以通过在体外通过高亲和力核酸配体连接干细胞表面受体来调节干细胞行为来解决。SomaLogic利用其专有的SOMAmer技术开发了这种适配体，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，以评估其潜力。该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，学生将有机会评估somamer与参与干细胞维持和分化的其他细胞表面分子。重要的是，该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粘附连接。利用詹姆斯实验室使用的共聚焦显微镜和蛋白质组学技术，他们将探索在引物和naïve多能干细胞中粘附连接形成的动力学，以及somamer对e-Cadherin下游信号通路的破坏作用。这些结果不仅对多能状态的维持提供了关键的启示，而且还为生物技术操纵提供了进一步的途径。非学术合作伙伴地点：SomaLogic位于科罗拉多州博尔德市一个设计精良的设施中，拥有约170名员工。该设施拥有约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住院期间，将提供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配体。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）学生计划支持。该项目招收的学生将加入DTP跨学科培训计划的学生群体，并将能够充分利用DTP提供的培训和交流机会。

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.