About the Project
This project will develop the first broadly applicable technology to identify carbon dioxide (CO₂)-binding sites on proteins, revealing a previously hidden layer of biological regulation with applications in biomedicine and sustainable biotechnology.
CO₂ is typically viewed as a metabolic waste product and major contributor to climate change. However, growing evidence suggests that CO₂ also acts as a biological signal that can directly regulate protein function. Human cells experience changing CO₂ concentrations during exercise, ageing and disease, while environmental CO₂ exposure is increasing through both indoor air quality challenges and long-term atmospheric change. Despite its importance, we still know remarkably little about where CO₂ binds proteins, how widespread these interactions are, and how they influence biological systems.
As society moves towards Net Zero emissions, new technologies are needed to transform CO₂ from a waste product into a valuable resource. Engineering biological systems that can capture and convert CO₂ into useful chemicals could become a cornerstone of sustainable manufacturing. Achieving these goals requires a much deeper understanding of how CO₂ interacts with proteins and regulates biological function.
We have previously developed methodologies to identify CO₂-mediated modification of lysine residues on proteins. These studies have advanced our understanding of inflammation, photosynthetic light harvesting and stress adaptation. However, lysine modification represents only one member of a much broader spectrum of protein-CO₂ interactions. This PhD will develop the first broadly applicable technology for mapping protein-CO₂ interaction sites, enabling discovery of the wider CO₂ interactome and revealing new mechanisms of biological regulation.
Success will provide the tools needed to identify previously unknown CO₂-responsive proteins in health and disease and to engineer enzymes that capture and convert CO₂ into valuable products, supporting future low-carbon biotechnology.
The supervisory team has an established track record in CO₂ biology, chemical biology and multidisciplinary research at the biosciences-chemistry interface.
To achieve these aims, the project will pursue three objectives that combine cutting-edge analytical chemistry with molecular biosciences to uncover previously inaccessible protein-CO₂ interactions.
- Characterise protein-CO₂ interactions using physical chemistry, chromatography, mass spectrometry and nuclear magnetic resonance (NMR).
- Develop and apply novel chemical tools to identify CO₂-binding sites in proteins.
- Determine how CO₂ binding influences protein structure, activity and biological function.
The successful candidate will help establish a new research field focused on understanding the molecular mechanisms by which proteins sense and respond to CO₂.
The project is ideally suited to students with a background in chemistry, biology, biochemistry, molecular biology or related disciplines. The student will receive training across both Biosciences and Chemistry, developing expertise beyond their original discipline. Training will include molecular biology, protein expression and purification, cell culture, chemical biology, NMR spectroscopy, chromatography, mass spectrometry, data analysis and computational methods. Graduates will develop a rare combination of experimental and quantitative skills that are highly sought after in academia, biotechnology and pharmaceutical industries.
This project is available to start in January 2027 or October 2027.
Please contact Professor Martin Cann (m.j.cann@durham.ac.uk) or Professor David Hodgson (d.r.w.hodgson@durham.ac.uk) for informal enquiries.
Funding Notes
The funding for this project is in place. Success will depend on the quality of the application relative to competing applications. Shortlisted candidates will be invited for an online interview soon after the closing date. If you are interested in applying, contact the supervisor (Professor Martin Cann, m.j.cann@durham.ac.uk) with a CV and covering letter detailing your reasons for applying for the project, no later than Friday 23rd October 2026. Candidates short-listed for interview will be asked to provide two references in support of their application.
References
Vadász, I., Cummins, E.P., Brotherton, D.H., Marina Casalino-Matsuda, S., Dada, L.A., Green, O., King, D.T., Kryvenko, V., Shigemura, M., Sporn, P.H.S., Strowitzki, M.J., Cann, M.J., Sznajder, J.I. (2025) Sensing molecular carbon dioxide – a translational focus for respiratory disease. Physiological Reviews. 105: 2657–2691 doi.org/10.1152/physrev.00022.2024
Guillen-Garcia, A., Gibson, S.E.R., Jordan, C.J.C., Ramaswamy, V.K., Linthwaite, V.L., Bromley, E.H.C., Brown, A.P., Hodgson, D.R.W., Blower, T.R., Verlet, J.R.R., Degiacomi, M., Pålsson, L-O., Cann, M.J. (2022) Allophycocyanin A is a carbon dioxide receptor in the cyanobacterial phycobilisome. Nature Communications. 13: 5289 doi: 10.1038/s41467-022-32925-6
Blake, L.I. & Cann, M.J. (2022) Carbon dioxide and the carbamate post-translational modification. Frontiers in Molecular Biosciences. 9:825706. doi: 10.3389/fmolb.2022.825706
Linthwaite, V.L., Pawloski, W., Pegg, H.B., Townsend, P.D., Thomas, M.J., So, V.K.H., Hodgson, D.R.W, Lorimer, G.H., Fushman, D., Cann, M.J. (2021) Ubiquitin is a carbon dioxide-binding protein. Science Advances. 7: eabi5507
Linthwaite, V.L., Janus, J.M., Brown, A.P., Wong-Pascua, D., O’Donoghue, A.C., Porter, A., Treumann, A., Hodgson, D.R.W., Cann, M.J. (2018) The identification of carbon dioxide mediated protein post-translational modifications. Nature Communications 9:3092 doi: 10.1038/s41467-018-05475-z