Mechanisms that modulate leukocyte migration in vivo are fundamental to the function of the immune system. Leukocytes such as neutrophils and macrophages are first-line responders to many physiological and pathological changes in the tissue microenvironment, such as inflammation after injury or in cancer. These cells sense various chemotactic cues and migrate through complex tissue landscapes with distinct directionality.
The function of leukocytes in cancer is well appreciated. However, little is known of the role of leukocytes during tumour initiation. Our previous work with zebrafish larvae has revealed a tumour-supporting role of neutrophils in this setting. Our live imaging studies allowed us to directly visualise neutrophil migration toward a cancerous cell at its inception, from which we observed heterogenous recruitment behaviour of neutrophils. Our single cell RNAseq analysis also revealed several distinct clusters of neutrophil subpopulations. However, mechanisms behind these difference in migratory behaviour remain to be elucidated. We also don’t know how functionality differs between different neutrophil subsets. In this project, we aim to combine computational modelling with in vivo live imaging in zebrafish larvae to characterise the migratory behaviour of different neutrophil subsets and determine whether there is a correlation between migration behaviour and functionality of different subsets.
We will develop a computational framework to analyse neutrophil dynamics in tumour initiation which would allow us to define each neutrophils subsets based on their migration behaviour. Subsets that interact the most with PNCs might play a more significant role in PNC progression. We aim to define migratory behaviour of each subset therein to generate testable hypotheses concerning the underlying molecular mechanism. Based on description and prediction from biophysical modelling, we will then explore the factors involved in vivo to test the hypotheses. More importantly, we will examine tumour progression under conditions where subsets of neutrophil recruitment are altered. Ultimately, a better understanding of how tumour promoting neutrophils sense the environment, integrate incoming signals, and navigate in vivo in tumour initiation will provide us with an opportunity to target tumour promoting neutrophils, and subsequently block tumourigenesis for therapeutic intervention.
The student will receive training in relevant ‘wet lab’ techniques and microscopy/image analysis while working with existing preliminary data and computational tools for modelling and analysis of immune cell migration. Ideal candidates would do both experimental and computational research.
This project is an excellent opportunity for students with previous experience in statistics and interest in computer programming. Students from physics, mathematics, engineering, computer science, or related degrees are encouraged to apply.
Funding information and Application Process:
This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership (DTP)
This opportunity is open to UK and international students and provides funding to cover stipend and UK level tuition fees. The University of Edinburgh will cover the difference between home and international fees meaning that the EASTBIO DTP will offer fully-funded studentships to all appointees. However there is a cap on the number of international students the DTP can recruit. It is therefore important for us to know from the outset which fees status category applicants will fall under when formally applying for entry to our university.
Please refer to UKRI Website and Annex B of the UKRI Training Grant Terms and Conditions for full eligibility criteria.
Informal enquiries should be addressed to Dr Feng. To apply, please send a cover letter outlining your previous research experience and reasons for applying, alongside an up-to-date CV to [Email Address Removed]
Download and complete our Equality, Diversity and Inclusion survey and then fill in the EASTBIO Application Form and submit it, along with a copy of your academic transcripts, to [Email Address Removed] before the application deadline.
You should also ensure that two references have been sent to [Email Address Removed] by the deadline using the EASTBIO Reference Form
We anticipate that our first set of interviews will be held 6th – 10th February 2023 with awards made in the following week.
If you have further queries about the application/recruitment process please contact [Email Address Removed]
The research group is located in the University of Edinburgh Centre for Inflammation Research; a world-class research environment at the interface between biological and medical science, with multidisciplinary groupings focused on inflammation, infection, disease and repair. The Centre is based within the Edinburgh Medical School in the outstanding facilities of the Queen’s Medical Research Institute at the site of the Royal Infirmary of Edinburgh hospital, maximising future translational opportunities
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