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Dr Kevin Webb
No more applications being accepted
Competition Funded PhD Project (Students Worldwide)
Nottingham
United Kingdom
Biomedical Engineering
Cell Biology
Genomics
Molecular Biology
Nanotechnology
Pollution
About the Project
In 2013 Ella Kiss-Debrah died of an asthma attack caused by illegally high levels of air pollution in London. Globally traffic related air pollution kills 2.4 million people. Despite this governments are “passing the buck” on action to reduce environmental levels. We understand remarkably little about which constituents of air pollution are detrimental to health or the mechanisms by which they impact on lung health. In this project we combine four leading edge research programmes at the (UoN) (UoN) and the (UoB) (UoB), supported by the respiratory theme of the NIHR Nottingham Biomedical Research Centre, to better understand which constituents of vehicle related PM damage airway cells and how. This project will use cutting-edge technologies and the expert support of the supervisory team to perform detailed characterisation of PM, use and develop novel in vitro airway cell models and profile the immune, remodelling and epigenetic profiles of airway cells. The student will learn fundamental and novel techniques across a broad repertoire including cell co-culture, advanced imaging, molecular biology/epigenetics, soot characterisation, epigenomics data analysis and R programming. The project includes cross institute learning, including the University of Nottingham Faculty of Engineering and School of Medicine and the University of Birmingham.
Enquiries
Project Enquiries to [Email Address Removed] - Applied Optics and Electrophysiology, Faculty of Engineering
Programme enquiries to [Email Address Removed]
To apply please refer to https://more.bham.ac.uk/mrc-aim/phd-opportunities/ for project opportunities and application form
Funding Notes
Competition Funded PhD Project (Students Worldwide) Closing date 10 January 2025 midday GMT
This is a fully funded Medical Research Council (MRC) studentship. Stipend and tuition fees are paid for 4 years at UKRI rates as well as there being a budget for project consumables, travel and a laptop to be purchased. The funder, UKRI, allows us to appoint up to 30% overseas students.
https://more.bham.ac.uk/mrc-aim/
References
1. Organisation WH. Air pollution: The invisible health threat. 2023.
2. organisation Wh. Air pollution is responsible for 6.7 million premature deaths every year.
3. Clifford RL, Jones MJ, MacIsaac JL, McEwen LM, Goodman SJ, Mostafavi S, et al. Inhalation of diesel exhaust and allergen alters human bronchial epithelium DNA methylation. The Journal of allergy and clinical immunology. 2016.
4. Clifford RL, John AE, Brightling CE, Knox AJ. Abnormal histone methylation is responsible for increased vascular endothelial growth factor 165a secretion from airway smooth muscle cells in asthma. Journal of immunology. 2012;189(2):819-31.
5. Clifford RL, Patel JK, John AE, Tatler AL, Mazengarb L, Brightling CE, et al. CXCL8 Histone H3 acetylation is dysfunctional in airway smooth muscle in asthma: regulation by BET. American journal of physiology Lung cellular and molecular physiology. 2015:ajplung 00021 2015.
Figure 1 - Experimental Concept: Engine exhaust and non-exhaust (tyre and brake) particles will create conditioned media for exposure to human airway models in the µSIM microphysiological platform, allowing the characterisation of both PM and cellular responses. Immune, remodelling and epigenetic features of the airway model will be profiled using targeted and global analysis techniques. PM provoking responses will be analysed chemically and morphologically.
6. Clifford RL, Patel J, MacIsaac JL, McEwen LM, Johnson SR, Shaw D, et al. Airway epithelial cell isolation techniques affect DNA methylation profiles with consequences for analysis of asthma related perturbations to DNA methylation. Sci Rep-Uk. 2019;9.
7. Clifford RL, Deacon K, Knox AJ. Novel regulation of vascular endothelial growth factor-A (VEGF-A) by transforming growth factor (beta)1: requirement for Smads, (beta)-CATENIN, AND GSK3(beta). The Journal of biological chemistry. 2008;283(51):35337-53.
8. McCloskey MC, Kasap P, Ahmad SD, Su SH, Chen K, Mansouri M, et al. The Modular microSiM: A Mass Produced, Rapidly Assembled, and Reconfigurable Platform for the Study of Barrier Tissue Models In Vitro. Adv Healthc Mater. 2022;11(18):e2200804.
9. La Rocca A, et al. Tribology International. 2013;61:80-7.
10. Orhan O, et al. Tribology International. 2016;104:272-84.
11. La Rocca A, et al. Characterisation of soot in oil from a gasoline direct injection engine using Transmission Electron Microscopy. Tribology International. 2015;86:77-84.
12. Bogarra M, Herreros JM, Tsolakis A, Rodríguez-Fernández J, York APE, Millington PJ. Gasoline direct injection engine soot oxidation: Fundamentals and determination of kinetic parameters. Combust Flame. 2018;190:177-87
2. organisation Wh. Air pollution is responsible for 6.7 million premature deaths every year.
3. Clifford RL, Jones MJ, MacIsaac JL, McEwen LM, Goodman SJ, Mostafavi S, et al. Inhalation of diesel exhaust and allergen alters human bronchial epithelium DNA methylation. The Journal of allergy and clinical immunology. 2016.
4. Clifford RL, John AE, Brightling CE, Knox AJ. Abnormal histone methylation is responsible for increased vascular endothelial growth factor 165a secretion from airway smooth muscle cells in asthma. Journal of immunology. 2012;189(2):819-31.
5. Clifford RL, Patel JK, John AE, Tatler AL, Mazengarb L, Brightling CE, et al. CXCL8 Histone H3 acetylation is dysfunctional in airway smooth muscle in asthma: regulation by BET. American journal of physiology Lung cellular and molecular physiology. 2015:ajplung 00021 2015.
Figure 1 - Experimental Concept: Engine exhaust and non-exhaust (tyre and brake) particles will create conditioned media for exposure to human airway models in the µSIM microphysiological platform, allowing the characterisation of both PM and cellular responses. Immune, remodelling and epigenetic features of the airway model will be profiled using targeted and global analysis techniques. PM provoking responses will be analysed chemically and morphologically.
6. Clifford RL, Patel J, MacIsaac JL, McEwen LM, Johnson SR, Shaw D, et al. Airway epithelial cell isolation techniques affect DNA methylation profiles with consequences for analysis of asthma related perturbations to DNA methylation. Sci Rep-Uk. 2019;9.
7. Clifford RL, Deacon K, Knox AJ. Novel regulation of vascular endothelial growth factor-A (VEGF-A) by transforming growth factor (beta)1: requirement for Smads, (beta)-CATENIN, AND GSK3(beta). The Journal of biological chemistry. 2008;283(51):35337-53.
8. McCloskey MC, Kasap P, Ahmad SD, Su SH, Chen K, Mansouri M, et al. The Modular microSiM: A Mass Produced, Rapidly Assembled, and Reconfigurable Platform for the Study of Barrier Tissue Models In Vitro. Adv Healthc Mater. 2022;11(18):e2200804.
9. La Rocca A, et al. Tribology International. 2013;61:80-7.
10. Orhan O, et al. Tribology International. 2016;104:272-84.
11. La Rocca A, et al. Characterisation of soot in oil from a gasoline direct injection engine using Transmission Electron Microscopy. Tribology International. 2015;86:77-84.
12. Bogarra M, Herreros JM, Tsolakis A, Rodríguez-Fernández J, York APE, Millington PJ. Gasoline direct injection engine soot oxidation: Fundamentals and determination of kinetic parameters. Combust Flame. 2018;190:177-87
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