Details
Inflammatory heart diseases are major causes of mortality worldwide and often result from infections in the heart, which fall into three main classes. Endocarditis is inflammation of the inner lining of the heart (endocardium), typically caused by circulating bacteria such as Staphylococcus aureus, becoming lodged in the heart through unknown mechanisms. Staphylococcus aureus can also cause myocarditis (inflammation of the myocardium, the contractile cells of the heart) and pericarditis (the sac around the heart). Cardiac infection can cause lasting damage to the heart, and the recent identification of myocarditis in patients with Sars-Cov2 infection highlights a need to better understand the mechanisms underlying heart infections. Despite this, few animal models of cardiac infection exist.
You will use zebrafish embryos infected with Staphylococcus aureus to understand the tissue and immune cell mechanisms involved in the development of heart infections. We hypothesise that the innate immune system plays key roles in the instigation of heart infections that can be therapeutically manipulated to improve infection outcomes.
You will use state-of-the-art fluorescence microscopy to:
1. Identify when, where and how Staphylococcus aureus infects the heart in a systemic infection model.
2. Determine whether innate immune cells participate in establishing heart infections.
3. Investigate mechanisms to improve innate immunity and reduce heart infection.
This project will exploit recently-established transgenic fish lines and cutting edge methodologies in the recently opened Wolfson Zebrafish Infection Laboratory. Zebrafish larvae will be infected systemically with fluorescent Staphylococcus aureus by microinjection into the caudal vein, around 20% of which develop cardiac infection. You will use cutting-edge confocal and lightsheet microscopy to define which cell types and cardiac structures are the primary site of infection, and to establish how infection progresses. Fluorescent microscopy will identify whether infected immune cells enter the heart. Innate immunity will be modulated to investigate whether heart infection can be controlled.
This project synergises the expertise of two successful groups from the faculties of Medicine and Science, using techniques that are well-established in our groups that have so far produced exciting results and requires an enthusiastic PhD student to take forwards. You will join two vibrant research groups (http://elkslab.weebly.com/, https://emilynoelresearch.weebly.com/) and you will be well trained in zebrafish biology and microscopy techniques, as well as writing and presenting your science.
You should possess a high grade in a relevant biological degree. Zebrafish laboratory experience is not required, but a passion for in vivo research is a must!
Entry Requirements:
Candidates must have a first or upper second class honours degree or significant research experience.
To be eligible for a CSC scholarship, you must:
- be applying to start a new full-time PhD programme at Sheffield
- have a strong academic background
- be a national of and reside in, mainland China (not including Hong Kong or Macau) – see CSC policies
- intend to return to China once your programme is completed
- hold a study offer from the University of Sheffield
- satisfy all of the CSC's selection criteria
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 ‘School of Medicine & Population Health: Infection Immunity & Cardiovascular Disease’ as the department.
Proposed start date - October 2024
For further information on the CSC scheme please see - https://www.sheffield.ac.uk/postgraduate/phd/scholarships/csc
Funding Notes
The University of Sheffield will fund tuition fees for 3.5 years. Students are expected to submit their thesis within this period. The China Scholarship Council (CSC) will fund a grant for living costs for up to four years, and one return flight from China to the UK.