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

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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.