MRC DiMeN Doctoral Training Partnership: Ageing-related susceptibility to pneumococcal pneumonia

Description

In this project, you will embark on an exciting research journey to understand how ageing makes us more vulnerable to the important bacterial pathogen, Streptococcus pneumoniae (pneumococcus). Based on the most recent Global Burden of Disease (GBD) study in 2021, the pneumococcus remains the most common non-COVID-19 cause of lower respiratory tract infections (LRI), responsible for an estimated 97.9 million LRI episodes and over half a million deaths globally. Invasive pneumococcal diseases (IPDs), most commonly pneumonia, are especially prevalent in young children (< 2 years) and older people (>65 years), contributing significantly to public health burden worldwide. Worryingly, the incidence and case fatality rates of IPDs remain at high levels in the elderly population since 1990 despite the wide coverage of the pneumococcal immunisation programme. As they age, older people can suffer from a decline in their immune system defence making them extremely vulnerable to infection.

To develop a clear understanding of how the ageing process alters host immunity and how this affects the local and systemic responses to pneumococcal infection, you will use clinically relevant murine challenge models to study pulmonary anti-pneumococcal responses. Together with high-throughput RNA sequencing, multiplexing protein analysis, immune cell phenotyping by flow cytometry, and state-of-the-art intravital imaging techniques, you will perform sophisticated spatial-temporal analysis of infected lungs thereby determining altered immune responses in aged lungs. The identified immunological targets will be tested in vitro with 3D respiratory cell co-culture models and in vivo by immune cell depletion, antibody neutralisation, etc. You will also aim to translate findings from mouse studies to human by setting up 3D cell co-culture models with human bronchus epithelial cells and peripheral blood mononuclear cells.

You will be strongly supported to develop a wide range of laboratory skills as described above, covering bacteriology, immunology and omics, and with training on critical thinking, communication and writing skills, that will set you apart from the competition post PhD. You will be encouraged to attend several international & national conferences, providing you with experience in presenting scientific findings and making important scientific connections. Our external collaboration with Imperial will provide you with a great opportunity to improve your adaptability and skills by working in a second lab. In addition, you will benefit from being a member of the vibrant department of Clinical Infection, Microbiology & Immunology at the University of Liverpool, with several research themes and seminars series and over 120 staff and students.

Your work will potentially lead to the discovery of novel biological targets that can improve the resistance of aged people to pneumococcal disease and open up a whole new avenue of research on how to reduce respiratory infection burden in the elderly by targeting ageing-related immune defects. You will also contribute to the development of the next stage of collaborations and grant funding applications by establishing new methodology and providing preliminary and/or publishable data.

To further discuss the project, please contact Prof. Aras Kadioglu (a.kadioglu@liverpool.ac.uk) and/or Dr. Rong Xu (xurong@liverpool.ac.uk).

Links to our lab and profile pages of the supervisors:

https://www.liverpool.ac.uk/bacterial-pathogenesis

https://www.liverpool.ac.uk/people/aras-kadioglu

https://orcid.org/0009-0005-8895-0303

https://profiles.imperial.ac.uk/f.puttur/about

Benefits of being in the DiMeN DTP:

This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle, York and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of-the-art facilities to deliver high impact research.

We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.

Being funded by the MRC means you can access additional funding for research placements, training opportunities or internships in science policy, science communication and beyond. Further information on the programme and how to apply can be found on our website:

https://www.dimen.org.uk/