Deciphering mechanisms of host-to-host transmission in pathogenesis of pneumococcal disease

Description

The major human pathogen Streptococcus pneumoniae (pneumococcus) is the main cause of pneumonia and meningitis worldwide and despite the global implementation of vaccine programmes, the burden of pneumococcal disease remains unacceptably high, especially in low-income countries. Based on the most recent Global Burden of Disease (GBD) study, the pneumococcus remains the most common (non-COVID) cause of lower respiratory tract infections (LRI), responsible for an estimated 97.9 million LRI episodes and over half a million deaths globally.

Asymptomatic carriage of pneumococci at the mucosal surface of the nasopharynx is the essential first step to invasive infection and acquiring the bacteria through transmission from colonised individuals is the route to establishing carriage. Host to host transmission occurs directly through inhalation of droplets and aerosols derived from an infected host, or indirectly following contact with contaminated fomites. Transmission is therefore a crucial stage in pneumococcal pathogenesis and disease, however, mechanistic detail on the bacterial and host factors which play key roles during transmission is limited.

In this project you will seek to address this knowledge gap by starting an exciting PhD research project in the Bacterial Pathogenesis and Immunity Group, to uncover the mechanisms controlling pneumococcal carriage and transmission. You will be trained in and use the latest in vitro and in vivo models of infection, FACS, proteomics and RNA-Seq transcriptomics to delineate the various processes involved. Your PhD will aim to understand how host to host transmission occurs and how we can develop novel strategies to stop it. You will also develop a clear understanding of how pneumococcal transmission and host immunity interact and how this affects the local and systemic host responses to pneumococcal infection.

You will use a newly developed clinically relevant mouse model of host-to-host transmission to study its key role in disease progression and pathogenesis. Together with high-throughput RNA sequencing, multiplexing protein analysis, immune cell phenotyping by flow cytometry, and state-of-the-art infection modelling techniques, you will aim to translate your findings from in vitro and in vivo studies to clinical studies.

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 international & national conferences, providing you with experience in presenting scientific findings and making important scientific connections. You will benefit from being a member of the vibrant department of Clinical Infection, Microbiology & Immunology at the University of Liverpool, with six research themes and internal and external speaker seminars series. and over 120 staff and students. Additionally, this PhD offers a great opportunity to spend time at the MHRA laboratories at its Science Campus in Potters Bar, Enfield. The remit of the laboratories is to develop methods and reagents to ensure vaccines are safe and effective. The Agency is in a unique position interacting with vaccine companies, academia and non-government organisations such as the World Health Organisation. As well as working with experts in the proteomics and sequencing groups, you will also have the chance to observe first-hand how a national regulator operates. Our supervisory team at the University of Liverpool together with scientists at the MHRA will provide great opportunities to demonstrate adaptability, develop a range of skills and have a taste of the different environments and challenges working within academia, government and industry. This range of experiences will support  you to design your career  at the end of your studies.

If you would like to further discuss the project, please contact Prof. Aras Kadioglu (a.kadioglu@liverpool.ac.uk)