Radiation injury is characterised by an influx of inflammatory cells. Macrophages have long been considered key cells in the tissue repair process, but they can have both beneficial and detrimental effects on damage resolution and tissue repair, depending on their phenotype and the niche they inhabit. The salivary glands (SG) are often inadvertently irradiated during treatment for head and neck cancer; however, our understanding of the cellular and molecular processes that govern effective tissue repair and regeneration in the irradiated SG remains incomplete. The Emmerson lab (1st supervisor) have recently demonstrated that distinct populations of macrophages exist in the mouse and human salivary glands. Furthermore, we have shown that irradiation (IR) injury causes significant changes in the phenotype of some of these populations, suggesting that IR injury may directly or indirectly influence macrophage functions. Finally, we have shown that in the absence of macrophages, epithelial DNA damage accumulates, demonstrating that macrophages are essential for efficient repair (in collaboration with the Bain lab, 3rd supervisor).
Next, we want to determine if macrophage phenotype is important for their role in SG repair after injury, and whether we can help SG regeneration occur more efficiently by specifically targeting the macrophages to develop a particular phenotype.
In this project the student will:
1. Characterise mouse SG macrophage polarisation at various timepoints after IR injury, with expert guidance and training from the Wilson lab (2nd supervisor)
2. Evaluate if particular SG macrophage subsets are more pro-regenerative than others
3. Manipulate mouse SG macrophage function in the days following IR injury, using the physiological inhibitors characterised by the Wilson lab (2nd supervisor).
Overall, this will determine if macrophage manipulation can be used as a therapeutic tool to promote salivary gland regeneration.
The student will use in vivo mouse models, ex vivo assays, cell culture, pharmacological experiments, multicolour flow cytometry and fluorescence-activated cell sorting (FACS), high powered confocal microscopy and transcriptional analysis, including the analysis of single cell (sc)-RNA-seq data, in order to address these aims. Furthermore, the student will gain experience in report writing, oral presentation, statistics and data management.
Application procedures:
EASTBIO How to Apply webpage
- EASTBIO Application
- Equality, Diversity and Inclusion (EDI) survey
- Reference Forms
(forms listed above can be downloaded here: http://www.eastscotbiodtp.ac.uk/how-apply-0)
Please send your completed EASTBIO Application Form and EDI survey along with a copy of your academic transcripts to [Email Address Removed] before the deadline.
You should also ensure that two references have been sent to [Email Address Removed] by the deadline using the EASTBIO Reference Form.
The EASTBIO team will run a series of 1-hour online sessions in November/December, open to applicants who have queries about the application process. Please view EASTBIO How to Apply webpage for details.
Unfortunately due to workload constraints, we cannot consider incomplete applications.
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