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  Should I stay or should I go now? Programming immune cell retention versus resolution at sites of tissue damage


   School of Medicine and Population Health

  , ,  Wednesday, June 26, 2024  Competition Funded PhD Project (Students Worldwide)

About the Project

The white blood cells known as macrophages are fundamental for development, homeostasis and defences against infections and altered self. However, macrophage dysfunction causes or exacerbates the majority of human disease conditions, especially those with an inflammatory component. Thus, targeting unrestrained or persistent association of immune cells at sites of pathology represents an approach to ameliorate a wide range of conditions including cancer, neurodegeneration and chronic inflammatory conditions such as COPD.

The complexity of the human innate immune system, difficulties of working in vivo with higher organisms and genetic redundancy in vertebrates, has meant that simpler model organisms have provided an attractive platform to investigate genetic control of macrophage function and inflammatory responses. As part of this, the fruit fly, Drosophila melanogaster, has been widely used to study the innate immune system and contains a blood cell population dominated by macrophage-like cells. These cells make rapid and robust responses to epithelial injuries (induced via laser ablation), with recruitment mechanisms conserved across evolution (Evans et al., 2015; Razzell et al., 2013; Yoo et al., 2011). Using flies, we have uncovered the important finding that Simu, a phosphatidylserine-binding receptor, contributes to retention of macrophages at wounds (Roddie et al., 2019).

In this project, you will dissect out the genetic mechanisms that enable retention of macrophages at sites of inflammation. While we are beginning to understand the genetic networks regulating this process, it is not clear how these genes dictate and govern cell-cell interactions at wound sites. Using cutting-edge, in vivo, fluorescent imaging, you will carefully examine the cell biology of immune-damaged cell interactions at these sites of damage. This careful characterisation will further inform and develop our understanding of these cell-cell fundamental interactions that contribute to inflammation and its resolution in vivo. Ultimately, you translate your finding to a vertebrate model (zebrafish larvae).

This project will suit applicants from a diverse range of backgrounds in their training, including cell biology, developmental biology, genetics and immunology. The successful applicant will display a passion for live imaging and microscopy and an appreciation for the use of model organisms in biomedical research. Our labs are part of the Bateson Centre (https://www.sheffield.ac.uk/bateson) and School of Medicine and Population Health at the University of Sheffield. We form part of a critical mass of innate immunity researchers combining genetic and imaging-based approaches making use of superb facilities such as the Wolfson Light Microscopy Facility, Sheffield Drosophila and Zebrafish Facilities. Sheffield is a fantastic place to live and study and we’d love you to consider joining our dynamic, fun and diverse team. Please do not hesitate to make informal enquiries via email ().

Entry Requirements:

Candidates must have a first or upper second class honours degree or significant research experience.

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 ‘School of Medicine and Population Health: Infection, Immunity and Cardiovascular Disease’ as the department.

Proposed start date - October 2024

Biological Sciences (4)

Funding Notes

The Faculty of Health is offering a number of scholarships for the academic year 2024/5 for eligible students. This project is being considered for both Faculty Scholarship and PGT>PGR (see below) scholarship schemes. Applicants do not need to apply more than once as they will automatically be considered for both scholarships based on their eligibility criteria.  Students worldwide are welcome to apply but will need to fund the overseas fee difference of around £24,000 per year

PGT>PGR

We are accepting applications from current and past (who have graduated in 2022 & 2023) PGT students from the Faculty of Health.


References

The scholarships cover tuition fees and a tax-free stipend at the UKRI rate (£19,237 for students starting in October 2024), as well as a training and development allowance.

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