Are macrophages the heroes or villains of infection control?

The field of host pathogen interactions has never been more important. From the recent Covid19 pandemic to the causes of cancer and neurodegenerative disease host pathogen interactions underpin the pathology of many important diseases. Coupled with the ongoing antimicrobial resistance pandemic, it is vitally important we understand infection in the context of the immune system and how that interaction might be targeted for treatment beyond the use antimicrobials. Macrophages have been studied in detail as effector and regulator cells in the immune response to infection. Despite such detailed investigation the critical aspect(s) of macrophages biology that go wrong in life threatening infection is unknown. For example, numerous studies by ourselves and others have demonstrated that macrophages in vitro are poor effector cells in controlling infection but are known to be essential for control in animal models and human disease. While genetic and molecular studies have identified many factors that are necessary and/or sufficient for different aspects of macrophage biology how these factors interact with each other and with other elements of the host and pathogen response are rarely reliably testable in current experimental models. A major reason for this is that what we measure as the outcome of infection is the result of many thousands of individual events, most of which are by their nature stochastic (random). Our research group is in a unique position to have comparable experimental model data from multiple different cellular, animal and human clinical models. Therefore, in this project we will use our existing published and unpublished data sets on host pathogen interactions to develop theoretical models of the function of macrophages in the outcome of different infections. A critical feature is that we have data that demonstrates both the detailed features of the relevant host pathogen interactions and the outcome of the infection. This means we can develop our models using known measurements and relevant biological features but can also test our models against the known outcome of infections, including human clinical trial data.

Entry Requirements:

Candidates must have a first or upper second class honors degree or significant research experience. Qualifications in mathematical subjects desirable but not essential.

How to apply:

Please complete a University Postgraduate Research Application form available here: https://www.sheffield.ac.uk/postgraduate/phd/apply/applying

Please clearly state the prospective main supervisor in the respective box and select Infection, Immunity and Cardiovascular Disease as the department.