Visualizing Filamentous Actin Using Synthetic Biology and Click Chemistry

项目描述：从细菌到人类的所有细胞中，细胞形态和形态组织的基础是细胞骨架（称为细胞骨架）。许多细胞骨架系统已经被描述，其中一个非常重要的是肌动蛋白细胞骨架，它在肌肉收缩和癌症转移中起着众所周知的作用。研究细胞骨架及其如何促进细胞功能（如细胞分裂、细胞迁移等过程）的最佳方法之一是使用先进的显微镜工具将其可视化，这可以使我们看到生物分子，甚至百万分之一毫米的大小。然而，构成肌动蛋白细胞骨架的关键蛋白质，肌动蛋白（形成聚合轨迹），很难用灯泡（荧光标签）标记，这将使其在显微镜下可视化。我们计划使用合成生物学方法在肌动蛋白细胞骨架的检测和成像方面做出一步改变，我们将在肌动蛋白中引入非天然氨基酸形式的超小把手。这些手柄将通过有机化学方法与荧光分子挂钩。将在肌动蛋白的多个位置，一次一个地引入灯泡，不干扰肌动蛋白功能的灯泡将用于高级成像实验。一旦方法建立，学生将在体外（在试管中，通过纯化细胞中产生的肌动蛋白）和体内（在生物体中使用先进的显微技术）研究肌动蛋白行为的许多方面。这些研究将为基础生物学以及癌症转移、心血管疾病等疾病提供重要的见解。项目概述：这个mrc资助的博士培训伙伴关系（DTP）将尖端的分子和分析科学与创新的数据分析计算方法结合在一起，使学生能够解决以假设为主导的生物医学研究问题。这是一个为期4年的课程，第一年包括一系列教学模块和两个基于实验室的研究项目，最终获得跨学科生物医学研究硕士学位。前两个学期包括一系列教学模块，让学生在多学科科学方面打下坚实的基础。学生还将参加一系列由分子、细胞和组织动力学、微生物学和感染、应用生物医学技术、人工智能和数据科学等领域的学术和行业专家主持的大师班。在第三学期和夏季学期，学生在他们选择的实验室进行两个为期11周的研究项目。

Project:Fundamental to the organization of cell morphology and form in all cells ranging from bacteria to human is its skeleton (termed the cytoskeleton). A number of cytoskeletal systems have been described, a very important one being the actin cytoskeleton, which is well known for its role in muscle contraction and cancer metastasis. One of the best ways to investigate the cytoskeleton and how it promotes cell function (in processes such as cell division, cell migration etc.) is to visualize it using advanced microscopic tools, which can enable us to see biological molecules even a millionth of a millimetre in size. However, the key protein that makes up the actin cytoskeleton, actin (which forms polymeric tracks), is difficult to label with light bulbs (fluorescent tags) that will enable its visualization in microscopy. We plan to make a step change in the detection and imaging of the actin cytoskeleton using synthetic biology approaches in which we will introduce ultra small handles in the form of unnatural amino acids into actin. These handles will be hooked onto fluorescent molecules through organic chemistry approaches. Light bulbs will be introduced at a number of locations in actin, one at a time, and the ones that do not perturb function of actin will be used in advanced imaging experiments. Once the methodology is established, the student will investigate many aspects of actin behaviour in vitro (in a test tube, through purification of the actin protein that was made in cells) and in vivo (in living organisms using advanced microscopic techniques). These studies should provide major insight into basic biology as well as diseases such as cancer metastasis, cardiovascular disorders, and more.Programme overview:This MRC-funded doctoral training partnership (DTP) brings together cutting-edge molecular and analytical sciences with innovative computational approaches in data analysis to enable students to address hypothesis-led biomedical research questions. This is a 4-year programme whose first year involves a series of taught modules and two laboratory-based research projects that lead to an MSc in Interdisciplinary Biomedical Research. The first two terms consist of a selection of taught modules that allow students to gain a solid grounding in multidisciplinary science. Students also attend a series of masterclasses led by academic and industry experts in areas of molecular, cellular and tissue dynamics, microbiology and infection, applied biomedical technologies and artificial intelligence and data science. During the third and summer terms students conduct two eleven-week research projects in labs of their choice.