Last Date: Friday, December 13, 2024
Supervisors: Dr Jason Powell, Dr Michael Mather
Competition Funded PhD Project (Students Worldwide)
Newcastle University MRC DiMeN Doctoral Training Partnership
About the Project
The adenoid is a mass of lymphoid tissue, covered in a surface epithelium, on the posterior wall of the nasopharynx which is closely associated to the middle ear via the eustachian tube. It is primarily composed of adaptive immune cells, including specialised subsets of T and B cells. It can be considered the immune sentinel of the upper airways and governs local and systemic immune responses to inhaled stimuli.
Ongoing work in our group has suggested compromised adenoidal immune function (particularly B cell maturation) in children with chronic localised inflammatory/infective conditions, such as otitis media.
To date, there have been few in vitro models of the adenoid in humans. Primary human tissue is critical as most animal species, such as rodents, do not have adenoids. This project therefore aims to establish and characterise a cell culture model of primary adenoid tissue obtained from children and adults.
The project will leverage cutting edge knowledge of adenoid immune composition from single cell sequencing data [previous Action Medical Research PhD fellowship]. Our group has extensive experience of novel advanced cell culture, including airway and middle ear, and access to relevant human clinical material.
Using paediatric and adult adenoid biopsies from patients undergoing surgery (ethical approval secured and samples biobanked) the student will develop monocultures and advanced air-liquid interface co-culture of adenoidal lymphoid and respiratory epithelial cells. Cellular composition of the cultures, including the formation of germinal centres, will be characterised. The project will then progress onto co-culture challenges; utilising cytokines, antigens, and live clinical isolates for common upper respiratory tract infection pathogens. Measuring local immune functions, including differential antibody (IgA/IgM/IgG) and cytokines production over the lifespan and in chronic diseases.
The findings of this project will have the potential to better understand upper airway immunology over the lifespan; including response to allergens and pathogens in early life and later, relevant to air-borne infection and allergy. Furthermore, the model can be utilised for other applications in the future, such as nasal vaccine delivery studies.
The project would provide comprehensive training in translational basic science. The student will have the opportunity to work with a broad group of basic scientists and clinical academics, developing a multitude of laboratory skills, such as; advanced cell culture and co-culture techniques, FACS flow cytometry, immunohistochemistry and WB/ELISA. Such skills are highly-transferable. The student will be supported by post-doctoral research scientists and academics working with the supervisory team/wider research group.
We would envisage the student having the opportunity to present this work at local, national and international meetings (identified by the supervisory team), with the prospect of presentation prizes. Peer-reviewed publication related to this work is highly likely.
Find out more about the supervisor team:
https://www.ncl.ac.uk/medical-sciences/people/profile/jasonpowell.html
https://haniffalab.com/team/michael-mather.html
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:
Funding Notes
Studentships are fully funded by the Medical Research Council (MRC) for 4yrs. Funding will cover tuition fees, stipend (£19,237 for 2024/25) and project costs. We also aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of full studentships to international applicants. Please read additional guidance here: View Website
Studentships commence: 1st October 2025
Good luck!
References
1. Talks BJ, Mather MW, Chahal M, Coates M, Clatworthy MR, Haniffa M. Mapping Human Immunity and the Education of Waldeyer’s Ring. Annu Rev Genomics Hum Genet. 2024 25:161-182. https://doi.org/10.1146/annurev-genom-120522-012938
2. Mather MW, Powell S, Talks B, Ward C, Bingle CD, Haniffa M, Powell J. Dysregulation of immune response in otitis media. Expert Rev Mol Med. 2021, 23: e10 https://doi.org/10.1017/erm.2021.10
3. Mather MW, Verdon B, Botting RA, Engelbert J, Delpiano L, Xu X, Hatton C, Davey T, Lisgo S, Yates P, Dawe N, Bingle CD, Haniffa M, Powell J, Ward C. Development of a physiological model of human middle ear epithelium. Laryngoscope Investig Otolaryngol. 2021, 6: 1167-1174 https://doi.org/10.1002/lio2.661
4. Powell J, Verdon B, Wilson JA, Simpson AJ, Pearson J, Ward C. Establishment of an immortalized human subglottic epithelial cell line. Laryngoscope. 2019, 129: 2640-2645 https://doi.org/10.1002/lary.27761
5. Mavin E, Verdon B, Carrie S, Saint-Criq V, Powell J, Kuttruff C, Ward C, Garnett J, Miwa S. Real-time measurement of cellular bioenergetics in fully differentiated human nasal epithelial cells grown at air-liquid-interface. Am J Physiol Lung Cell Mol Physiol. 2020, 318: L1158-L1164 https://doi.org/10.1152/ajplung.00414.2019
6. https://cancertools.org/cell-lines/sg01-153460/
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