Characterisation of Staphylococcus aureus interactions with bone cells

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

Abstract

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:
Staphylococcus aureus is a bacterium responsible for infections ranging from minor abscesses to severe endocarditis. It is a leading cause of hospital-acquired infections. The rise in drug resistant strains of S. aureus, such as methicillin resistant S. aureus (MRSA), has made effective management of staphylococcal infections challenging. A major type of infection caused by S. aureus is the bone and joint infections, particularly those associated with prosthetic joints. Prosthetic joint infections (PJI) are often very serious, with high rates of chronic infections, which are extremely hard to eradicate. In addition to treatment, accurate clinical diagnosis of chronic PJI is also hard, due to a lack of reliable diagnostic tools.

S. aureus is able to effectively invade bone cells, where it is protected from antibiotics and our immune responses. Intracellular bacteria survive and multiply within our cells and have been strongly linked to chronic infections. The cell pathways that are modulated by the bacterium during intracellular infection remain unclear, and identification of these could aid early diagnosis and provide new drug targets.

The aim of this project is to identify bacterial and host proteins that are key to bone cell infection. Additionally, it will explore novel antibiotic delivery systems against intracellular S. aureus. During this project, we will use immunofluorescence confocal microscopy to characterise the intracellular bone cell infection profiles of S. aureus and functional genomics methods (RNA-seq) to identify genes that are regulated during infection. We will also synthesise novel antibiotic delivery systems against intracellular S. aureus using antimicrobial polymers. During this project the student will receive training in polymer chemistry methods and in quantitative skills such as live microscopy and bioinformatic analysis.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
MR/N014294/1 01/10/2016 30/09/2025
2269252 Studentship MR/N014294/1 01/10/2019 30/12/2023