Toward improved rapid diagnostics for carbohydrate biomarkers: Mapping epitope-paratope interactions that drive glycan recognition

项目概述：这个由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数据分析中的创新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年的计划，其第一年涉及一系列教学模块和两个基于实验室的研究项目，导致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中获得坚实的基础。学生还参加了一系列由学术和行业专家领导的大师班，这些专家在分子，细胞和组织动力学，微生物学和感染，应用生物医学技术以及人工智能和数据科学领域。在第三和夏季学期，学生在他们选择的实验室进行两个为期11周的研究项目。项目概述：快速准确地检测和诊断结核病和糖尿病等疾病，对疾病的严重程度和治疗有很大的影响。糖分子作为这些疾病的重要生物标志物，并且在免疫测定中以非常低的浓度被高选择性抗体识别。然而，这些识别事件的分子基础目前知之甚少，并且抗体的性能存在广泛的可变性，原因尚不清楚。在这项工作中，我们将探索抗体-糖相互作用的三维结构和化学动力学，以了解抗体直接识别碳水化合物的一般特征。这将使用跨学科的方法结合化学，生物物理学和分子生物学的方法来实现，以产生和表征来自具有重要医学意义的抗体的蛋白质和蛋白质片段。这些结果将形成高亲和力抗体相互作用的合理工程的基础，这将增强诊断测定对糖靶的灵敏度。 该项目是沃里克化学的狄克逊实验室与诊断侧流技术的领导者Mologic之间的合作。作为该项目的一部分，学生将接受定量技能（数据分析和结构和结合特性的计算）和将化学/物理方法应用于生物问题的跨学科技能的培训。

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. Project overview:Rapid and accurate detection and diagnosis of diseases such as tuberculosis and diabetes can have strong implications in the severity and treatment of the disease. Sugar molecules act as important biomarkers for these diseases and are recognized at very low concentrations by highly selective antibodies in immunoassays. However, the molecular basis of these recognition events is currently poorly understood, and there is wide variability in the performance of antibodies for reasons that remain unclear. In this work, we will probe the three-dimensional structures and chemical kinetics of antibody-sugar interactions to understand in general terms what features direct carbohydrate recognition by antibodies. This will be achieved using an interdisciplinary approach combining methods in chemistry, biophysics and molecular biology to produce and characterize proteins and protein fragments derived from antibodies of significant medical interest. These results will form the basis of rational engineering of high affinity antibody interactions that will enhance the sensitivity of diagnostic assays to sugar targets. This project is a collaboration between the Dixon laboratory in Warwick Chemistry and Mologic, a leader in diagnostic lateral flow technology. As part of this project the student will receive training in quantitative skills (data analysis and calculations of structure and binding properties) and interdisciplinary skills in applying chemical / physical methods to biological problems.