GW4 BioMed3 MRC DLP PhD project: Do respiratory cilia sense and signal infection?

About the project

About the Project This project is one of several in competition for funding from the GW4 BioMed3 MRC Doctoral Landscape Programme (DLP), which is offering up to 17 studentships for entry in September 2027. The partnership brings together the Universities of Bath, Bristol, Cardiff and Exeter to develop the next generation of biomedical researchers. Students will have access to the combined research strengths, training expertise and resources of the four research-intensive universities. More information may be found on the DLP’s website . Please note that the application process may close early to either home or international candidates (or both) before the stated deadline if an unprecedented number of applications are received – check the DLP’s website for details and updates. Supervisory Team: Prof Andrew Preston (University of Bath) Prof Kirsty Wan (University of Exeter) The Project : Respiratory cilia are largely regarded as purely mechanical, sweeping particles trapped in mucus out of the respiratory tract. However, they contain key signalling molecules, suggesting sensory and response functions. We will investigate this uncharacterised aspect of cilia biology. We will exploit the exquisite specificity of Bordetella bacteria for adherence to respiratory cilia that involves several different protein adhesins that engage currently unknown cilia receptors to alter ciliary beat patterns. We will characterise adhesin-receptor interactions, intra-cilia signalling induced by receptor engagement and the results of this signalling. This will redefine our understanding of sensing and responses at the respiratory epithelium surface. In this project we ask: ‘what is the role of cilia-specific signalling in sensing and responding to bacterial adherence?’ Our objectives are: 1. Define the ciliary receptors for binding to Bordetella adhesins. Preliminary evidence suggests cilia glycosphingolipids (GSLs) are bound directly by adhesins. 2. Identify intracellular signalling initiated in response to bacterial adherence, including mutants deficient for specific adhesins, and engagement of receptors by specific, purified adhesins bound to microsphere beads. Preliminary evidence implicates Ca 2+ signalling as critical to control of ciliary beat, but other key secondary messengers will be investigated along with the effect of antagonists of the signalling pathways mentioned above. 3. Identify the intercellular effects of signalling by analysing the secretion of cytokines from epithelial cultures in response to ciliary signalling. Blocking specific signalling pathways with specific antagonists will identify signal-cytokine pathways. 4. Model the effect of altered ciliary beat of fluid flow dynamics. Ciliary beat will be modulated using bacteria and adhesin binding, and the use of signalling pathway antagonists. The clearance function of cilia involves the movement of the overlying fluid phase by ciliary beat, but the control of this by coordinated ciliary beat, and the biophysics of this are poorly understood. To do this we will use organ culture and differentiated respiratory epithelial cell culture models. These will be used for high-speed imaging and modelling of cilia-driven fluid flows, work that will take place in the Wan lab at Exeter. Differentiated airway epithelial cultures, differentiated at the air-liquid interface will be used for analysis of signalling using high resolution confocal microscopy and cytokine responses using ELISA analysis of basal compartment fluids. This is a multi-disciplinary project seeking to discover novel aspects of respiratory mucosal biology and host-pathogen interactions. The student will benefit from the combined expertise and facilities of the Preston and Wan labs and the Universities of Bath and Exeter, and receive training in both wet lab and computational approaches. Requirements: Applicants must have obtained, or be about to obtain, a first or upper second-class UK honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of medical sciences, computing, mathematics or the physical sciences. Applicants with a lower second-class degree will only be considered if they have a grade of Merit or above in a master’s degree. Academic qualifications are considered alongside significant relevant non-academic experience. Non-UK applicants will also be required to have met the English language entry requirements of the University of Bath. Enquiries and Applications: Informal enquiries are welcomed and should be directed to Prof Preston: ap753@bath.ac.uk Formal applications must be submitted direct to the GW4 BioMed3 DLP using their online application form . A list of all the projects and details on how to apply are available DLP’s website . You may apply for up to 2 projects and submit one application per candidate only. APPLICATIONS CLOSE AT 17:00 (GMT) ON 21 OCTOBER 2026. IMPORTANT: You do NOT need to apply to the University of Bath at this stage – only those applicants who are successful in obtaining an offer of funding from the DTP will be required to submit an application for an offer of study from Bath. Equality, Diversity and Inclusion: We value a diverse research environment and aim to be an inclusive university, where difference is celebrated and respected. We welcome and encourage applications from under-represented groups. If you have circumstances that you feel we should be aware of that have affected your educational attainment, then please feel free to tell us about it in your application form. The best way to do this is a short paragraph at the end of your personal statement.

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