Mechanistic single-molecule studies of coronavirus replication and host interactions

Lead Research Organisation: University of Warwick
Department Name: Warwick Medical School

Abstract

DTP 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:
Coronaviruses (CoVs) infect a wide variety of animals and birds and can also cause severe disease in humans. The emergence of the novel SARS-CoV-2 virus at the end of 2019 has resulted in the ongoing Covid-19 pandemic that has infected millions of people and caused worldwide social and economic disruption.

In spite of the devastating impact of coronaviruses, many questions regarding the exact molecular details of how they replicate remain unanswered. For example, it is unknown how different parts of the viral genome interact with each other, the precise roles of many of the viral proteins that are involved in viral replication, or even the exact sites of viral replication in host cells. The need for fundamental research into coronaviruses, which can guide the development of novel treatments, is therefore vital.

To date, our knowledge of CoV replication has relied on data obtained using ensemble methods that report on the mean properties of billions of molecules, averaging the measured parameters over the entire molecular population. Single-molecule techniques allow real-time studies of viral replication with the advantage that they can provide direct observations of just one molecule at a time.

The aim of this project is to use single-molecule imaging to study coronavirus replication, using avian IBV and human SARS-CoV-2 as model viruses, and identify important stages of the life cycle that can be targeted with antiviral inhibitors.

The student will gain interdisciplinary skills at the interface of biology, virology and physics, using a wide range of techniques (protein expression and purification, protein labelling, biochemical and biophysical characterisation of protein/RNA interactions, single-molecule FRET, super resolution microscopy, quantitative image analysis, cell culture, virus infectivity assays etc.).

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
MR/N014294/1 30/09/2016 29/09/2025
2429523 Studentship MR/N014294/1 04/10/2020 31/12/2024