Research interests/description of main research theme:
Cigarette smoking is the most common cause of chronic obstructive pulmonary disease (COPD), a progressively debilitating lung disease which is currently the fourth leading cause of death worldwide(1). It is characterised by chronic inflammation, involving complex and dysregulated expression of many inflammatory mediators and exaggerated proteinase release(2). Patients experience a decreasing quality of life, most notably due to symptoms including breathlessness, cough and periods of exacerbation of their symptoms which may lead to hospitalisation and death(1).
Smoking cessation is the only known strategy that limits the accelerated decline seen COPD patients(1). Yet the prevalence of smoking in COPD patients in the UK remains much higher than in the general population, with estimates as high as 35%(3). However, the proportion achieving smoking cessation within trials is low, with over 80% relapsing within a year(4).
Electronic cigarettes (ECs) are commercially available non-medicinal devices that vapourise a liquid which usually contains nicotine and is inhaled. They are emerging as a viable alternative to cigarette smoking, with considerable potential to replace and eventually eradicate conventional cigarettes(5). In the UK, an estimated 3.2 million adults use ECs, and of these 1.6 million have completely stopped smoking.
Current evidence suggests that use of ECs is substantially less harmful to health than smoking(6). However, the extent of any long-term adverse effects of ECs remains unknown, especially when compared to other means of smoking cessation or continued smoking. Many questions remain about their effectiveness and safety, especially in chronic EC users with existing lung conditions.
COPD is thought to develop from the direct effect of inhaled irritants in susceptible subjects and hence patients might already be more vulnerable to any irritant effects of ECs(7). Given this unique susceptibility, studying the effects of vaping specifically in COPD patients is necessary. This would also advance our knowledge of the effects of vaping on the lungs faster than measuring the effect of vaping in “healthy” smokers who, by definition are more resistant to the damaging effects of irritants and hence any negative effects may take much longer to manifest.
Our group has considerable experience in studying airways inflammation, signals of COPD pathogenesis and neutrophil function, EC modelling, and recruitment to clinical cohorts and thus are ideally placed to deliver this project.
Our work (8) has demonstrated the impact of EC exposure in primary non-smoker alveolar macrophages (AM) and neutrophils, altering key effectors functions (neutrophils) and markers of inflammation; proteinase release, exaggerated ROS production and cytokines (AM), mirroring studies of COPD pathogenesis(9,10)
Using COPD innate immune cell models, this project will examine the effects of acute and chronic EC and cigarette smoke extract (CSE) exposures. Proposed mechanisms of action will be tested further in a human precision cut lung slice exposure model. Finally, these findings will be compared against those from COPD patients enrolled in the ECAL clinical trial, yielding a valuable insight into the chronic effects of vaping in COPD patients
In this project we aim to:
1. Characterise the effect of e-cigarettes on alveolar macrophages from COPD patients, in comparison to CSE.
2. Characterise the effects of e-cigarettes on neutrophils from COPD patients in comparison to CSE.
3. Examine the chronic effects of e-cigarettes using precision cut lung slices (PCLS) model.
4. Examine the effects on systemic proteinase activity and neutrophil function in COPD patient samples from the ECAL trial.
We are a friendly multi-disciplinary and collaborative group where PhD students, postdoctoral researchers and clinical teams support each other in sample collection, lab work and troubleshooting. Our PhD students have won many national/ international prizes for their work, presenting at conferences in Europe and the USA and have gone on to gain post-doctoral fellowships, working in academia, industry and national funding bodies.
Person Specification
Applicants should have:
• A strong background in biomedical science/biochemistry,
• Ideally a background in primary cell isolation and flow cytometry
• Skills in molecular biology such as qPCR are desirable.
• A commitment to Respiratory research in Respiratory disease
• An upper Second Class Honours Degree in a relevant Biomedical sciences degree.
How to apply
Informal enquiries are strongly encouraged and should be directed to [Email Address Removed]
Applications should be directed to Dr. Scott ([Email Address Removed]) . To apply, please send:
• A detailed CV, including your nationality and country of birth;
• Names and addresses of two referees;
• A covering letter highlighting your research experience/capabilities;
• Copies of your degree certificates with transcripts;
• Evidence of your proficiency in the English language, if applicable.
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