Circadian rhythms are thought to regulate all cells, including those making up the immune system. Circadian rhythm is exerted via clock-genes and is a likely reason for the increased risk of infections observed in jet-lagged individuals, or those doing shift work.
Neutrophils are the most abundant circulating immune cells in humans and represent a first line of defence against infections. These important innate immune cells are equipped with a set of specialised functions that allow them to detect, and kill microbes quickly. Neutrophils leave the blood stream and follow so-called chemoattractants to sites of infections, where they phagocytose and kill germs using cytotoxic compounds intracellularly. Alternatively, they expel strands of chromatin decorated with cytotoxic proteins, so-called neutrophil extracellular traps (NETs), to kill germs extracellularly.
Neutrophils are only short-lived, with fresh cells generated continually by granulopoiesis. New cells are released into the circulation daily in a tightly controlled, circadian fashion. Circulating neutrophils age throughout the day; this causes their upregulation of cell surface markers, and triggers homing of aged circulating neutrophils to sites of haematopoiesis. The aged neutrophils undergo apoptosis and are cleared in an immunologically silent fashion.
This PhD project will test how cellular age affects the neutrophils’ ability to kill in vitro and in vivo. Human neutrophils will be prepared from blood of healthy volunteers at the beginning and end of the working day. Tests will be performed to establish their cellular age, and, in parallel, their ability to detect and kill bacteria intracellularly and extracellularly. These experiments will identify whether neutrophil age is synchronised in the volunteers, and whether neutrophil age does indeed affect bacterial killing by neutrophils in vitro.
Despite their importance, neutrophils are comparatively poorly understood because they cannot be cultured or genetically modified. For a more tractable system, further experiments will be carried out in zebrafish larvae which have fluorescently labelled neutrophils. Unlike with human volunteers the day night rhythm of zebrafish can be manipulated. The translucent larvae allow us to study neutrophil chemotaxis and bacterial killing in vivo using microscopy. Importantly, zebrafish are amenable to genetic modification, allowing us to knock out genes of interest with relative ease.
The supervisory team of this project is expert in neutrophil (SV) and zebrafish (YF) biology. The student will join both labs, effectively becoming a member of two teams. The project would suit a student with a background in biological sciences, immunology, developmental biology or cell biology.
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 Vermeren. 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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