Area
Medicine
Location
UK Other
Closing Date
Friday 02 January 2026
Reference
MED2040
School of Medicine
Closing date: 2 January 2026
Start date: 1 February 2026
Defining mechanisms underlying post-translational modification of airway mucus and the impact on mucociliary function.
Supervisors: Ian Sayers, Cathy Merry (Nottingham), Gleb Yakubov (Leeds), David Thornton (Manchester), Luke Bonser (AstraZeneca)
Chronic sputum production is debilitating and a feature shared by several respiratory diseases including, asthma, chronic obstructive pulmonary disease and bronchiectasis; together chronic respiratory diseases are the 3 rd leading cause of death globally.
We have recently identified genetic variants regulating fucosyltransferase 2 ( FUT2 ) levels that are associated with chronic sputum production, cough and importantly, reduced lung function, suggesting a significant role for this gene in mucociliary function. Regulation of post-translational modifications is complex and can involve a range of mechanisms e.g. fucosyltransferases catalyse the attachment of fucose to glycan chains and fucosylation (and glycosylation) of proteins modulate their structure, stability and function. FUT2 has been implicated in several biological processes including modifying mucins (e.g. glycosylation of MUC5AC, modifying gel-forming capabilities), virus-host interactions, infection and cell-cell interactions. We hypothesise that alterations in proteins related to post-translational mechanisms including FUT2 significantly impacts the properties of the main lung gel-forming mucins MUC5AC and MUC5B which subsequently affects mucus function (e.g. mucociliary clearance) in airway health and disease.
This study will use physiologically relevant models e.g. human airway epithelial air liquid interface using cells isolated from different patient groups combined with molecular biology approaches to mechanistically determine the key regulatory processes determining expression, activity and functional impact of key genes including FUT2 . This will include CRISPRi to systematically silence DNA regions e.g. for FUT2 on chromosome 19 implicated by the set of genetic variants and identify key regulatory regions. Similarly, we will use CRISPR/Cas9 to reduce/delete/induce relevant modifying enzyme genes and study the effects of these manipulations in the context of inflammation and during viral infection. The functional consequences of modifying enzyme gene regulation on mucus levels, composition (particularly MUC5AC and MUC5B mucins), organization and properties (e.g. proteomics, glycomics, rheology, supramolecular network organization) will be identified. Cilia function/mucociliary clearance will be characterized using high speed microscopy. Mucus properties in sputum isolated from patients including the impact of carrying specific genetic variants will also be investigated.
This studentship brings together a highly collaborative team of researchers with a wealth of expertise in respiratory genetics/airway cell models (Sayers), mucins, biophysical analyses (Yakubov, Thornton), complex glycans (Merry), and mucus targeting (Bonser). This studentship will include a placement at Astra Zeneca, Cambridge and is part of a broader Medical Research Council Programme grant focused to understand mucus regulation in severe asthma.
The project will provide a significant opportunity for training in cutting edge methodologies and will lead to a significant shift in the mechanistic understanding of mucus regulation in the airways with therapeutic value.
Funding notes
The three year studentship covers UK tuition fees and a tax-free stipend.
Entry requirements:
At least a 2.1 Honours degree in Biochemistry, Biomolecular Science or a related field.
Informal inquiries can be made to ian.sayers@nottingham.ac.uk
Application details: to apply for this PhD opportunity, please submit the following documents to ian.sayers@nottingham.ac.uk
- Cover letter outlining your research interests and motivation to pursue this project.
- Curriculum vitae detailing your academic background, research experience, and relevant skills.
- Academic transcripts of your previous degrees.
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