synthesis, the universal energy currency of life. While electron pathways and individual intra-protein proton steps are partially mapped, the broader “proton circuitry”, encompassing dynamic proton hopping on membrane interfaces, cooperative water networks, and inter-protein communication, remains one of the central unsolved mysteries of physical biology. The key barrier to solving this puzzle has been a lack of methodologies capable of tracking proton movement with sufficient spatial and temporal resolution.
Novel Methodologies and Experimental Approach
Supervised by Prof. Nadav Amdursky at the University of Sheffield, this project leverages two pioneering, state-of-the-art methodologies developed exclusively within our research group to directly map biological proton circuitry:
- Light-Triggered Proton Probes and Ultrafast Spectroscopy: We synthesise custom-designed photoacids and photobases, which are molecules that release or absorb protons instantaneously upon light excitation. By strategically positioning these probes within protein structures or directly on membrane surfaces, we use ultrafast fluorescence and infrared (IR) spectroscopy to track proton transfer dynamics in real time across sub-nanosecond timescales.
- Solid-State Bioelectronics and Hydration Control: We integrate biological components into specialised bioelectronic devices equipped with custom proton-transparent electrodes. By operating under controlled atmospheric environments, we can systematically tune hydration levels to isolate the exact role of interfacial water in proton transport, measuring lateral conduction across membrane surfaces (hundreds of nanometres) and vertical translocation through membranes (~5 nanometres).
Project Scope and Interdisciplinary Customisation
Because these novel methodologies unlock vast unexplored research avenues, the specific biological and chemical focus will be tailored to match the chosen candidate’s background, interests, and career ambitions. Depending on your desired technical training, the research can emphasise:
- Biochemistry & Molecular Biology: Engineering, expressing, and reconstituting functional transmembrane transport proteins into model lipid bilayers.
- Organic Chemistry & Chemical Biology: Synthesising novel site-specific molecular probes, photoacids, and functionalized transmembrane peptides.
- Biophysics & Bioelectronics: Fabricating micro-scale bioelectronic devices and performing advanced optoelectronic and spectroscopic characterisation.
Broader Implications and Research Environment
Beyond resolving fundamental questions in physical chemistry and biophysics, this research carries broad translational implications. Deciphering bioenergetic proton pathways is vital for understanding mitochondrial diseases, metabolic dysfunction, and cellular aging, while simultaneously inspiring new bio-informed materials for clean energy harvesting and next-generation protonic bio-interfaces.
Joining our group provides an exceptional, cross-disciplinary PhD environment spanning physical chemistry, molecular biology, organic synthesis, physics, and electrical engineering. As a PhD researcher in our group, you will benefit from comprehensive technical training, a supportive research community, and strong integration into an active global network of international collaborators.
Funding Notes
This is a faculty-funded studentship for home students only.
References
https://sheffield.ac.uk/mps/people/all-academic-staff/nadav-amdursky
