Using EPR spectroscopy to probe electron transfer in biology: from model molecular wires to complex metalloenzymes

A fully funded PhD position is available in the Roessler research group as part of the Centre for Pulse EPR spectroscopy (PEPR). PEPR is a major new facility at Imperial College London and was recently launched at the White City Campus. The Roessler group investigates unpaired electrons in redox reactions that underpin essential chemical reactions in respiration and photosynthesis. We apply pulse EPR techniques [1] to understand the mechanisms of challenging enzymes that cannot be obtained in high concentrations and require precise electrochemical potential adjustment [2,3]. We are also developing film-electrochemical EPR spectroscopy (FE-EPR), an exciting technique for studying the evolution of radicals during a reaction [4]. FE EPR allows the accurate determination of the redox potentials of buried redox centres within enzymes and their activity during catalysis. PEPR combines pulse EPR at X- and Q-band frequencies with FE-EPR and instrument development in collaboration with University College London and the London Centre of Nanotechnology [5].
In this project, you will apply the state-of-art instrumentation available at PEPR, together with the unique capabilities of FE-EPR, to build on our recent findings of electron transfer within photosynthetic complex I [2] and energy-coupling in respiratory complex [3]. You will acquire a fundamental understanding of how best to harness the recent advances in pulse EPR to investigate complex paramagnetic centres using model molecular wires. Using this foundation, we will study how complex I type enzymes use electron transfer to pump protons that are essential for ATP synthesis. The project is interdisciplinary and collaborative, and depending on your choice of focus for your project you will have the opportunity to combine physics/physical chemistry (advanced EPR, electrochemistry), material science (for the fabrication and characterisation of electrodes), biochemical methods (making and manipulating membrane proteins) and chemical synthesis (making model molecular wires). You should have a keen interest and background in physical chemistry or biochemistry. Previous exposure to EPR spectroscopy is an asset but not an essential requirement.
[1] M. M. Roessler and E. Salvadori, 'Principles and Applications of EPR Spectroscopy in the chemical sciences', Chemical Society Reviews, 2018, 47 (8), 2534-2553
[2] K.H. Richardson, J.J. Wright, M. Simenas, J. Thiemann, A.M. Esteves, G. McGuire, W.K. Myers, J.J.L. Morton, M. Hippler, M.M. Nowaczyk, G.T. Hanke, M.M. Roessler, 'Functional basis of electron transport within photosynthetic complex I', Nature Communications, 2021, 12, 5387, Press Release
[3] N. le Breton, J. J. Wright, A.J.Y.J. Jones, E. Salvadori, H. R. Bridges, J. Hirst, M. M. Roessler, 'Using EPR Hyperfine Spectroscopy to define the Proton-Coupled Electron Transfer Reaction at Fe-S cluster N2 in Respiratory Complex I', J. Am. Chem. Soc., 2017, 139 (45), 16319-16326, Spotlight Article
[4] K. Abdiaziz, E. Salvadori, K.P. Sokol, E. Reisner, M.M. Roessler, 'Protein film electrochemical EPR spectroscopy as a technique to investigate redox reactions in biomolecules', Chemical Communications, 2019, 55 (60), 8840-8843
[5] M Simenas, J O'Sullivan, CW Zollitsch, O Kennedy, M Seif-Eddine, I Ritsch, M Hulsmann, M Qi, A Godt, MM Roessler, G Jeschke, JJL Morton, 'A sensitivity leap for X-band EPR using a probehead with a cryogenic preamplifier', Journal of Magnetic Resonance 2021 322, 106876

Addressing UK skills demand: The most important impact of the CDT will be to train a new generation of Chemical Biology PhD graduates (~80) to be future leaders of enterprise, molecular technology innovation and translation for academia and industry. They will be able to embrace the life science's industrialisation thereby filling a vital skills gap in UK industry. These students will be able to bridge the divide between academia/industry and development/application across the physical/mathematical sciences and life sciences, as well as the human-machine interfaces. The technology programme of the CDT will empower our students as serial inventors, not reliant on commercial solutions.
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UK plc: The technologies generated by the CDT will produce IP with potential for direct commercial exploitation and will also provide valuable information for healthcare and industry. They will redefine the state of the art with respect to the ability to make, measure, model and manipulate molecular interactions in biological systems across multiple length scales. Coupled with industry 4.0 approaches this will reduce the massive, spiralling cost of product development pipelines. These advances will help establish the molecular engineering rules underlying challenging scientific problems in the life sciences that are currently intractable. The technology advances and the corresponding insight in biology generated will be exploitable in industrial and medical applications, resulting in enhanced capabilities for end-users in biological research, biomarker discovery, diagnostics and drug discovery.
These advances will make a significant contribution to innovation in UK industry, with a 5-10 year timeframe for commercial realisation. e.g. These tools will facilitate the identification of illness in its early stages, minimising permanent damage (10 yrs) and reducing associated healthcare costs. In the context of drug discovery, the ability to fuse the power of AI with molecular technologies that provide insight into the molecular mechanisms of disease, target and biomarker validation and testing for side effects of candidates will radically transform productivity (5-10 yrs). Developments in automation and rapid prototyping will reduce the barrier to entry for new start-ups and turn biology into an information technology driven by data, computation and high-throughput robotics. Technologies such as integrated single cell analysis and label free molecular tracking will be exploitable for clinical diagnostics and drug discovery on shorter time scales (ca.3-5 yrs).
Entrepreneurship & Exploitation: Embedded within the CDT, the DISRUPT tech-accelerator programme will drive and support the creation of a new wave of student-led spin-out vehicles based on student-owned IP.
Wider Community: The outreach, responsible research and communication skill-set of our graduates will strengthen end-user engagement outside their PhD research fields and with the general public. Many technologies developed in the CDT will address societal challenges, and thus will generate significant public interest. Through new initiatives such as the Makerspace the CDT will spearhead new citizen science approaches where the public engage directly in CDT led research by taking part in e.g hackathons. Students will also engage with a wide spectrum of stakeholders, including policy makers, regulatory bodies and end-users. e.g. the Molecular Quarter will ensure the CDT can promote new regulatory frameworks that will promote quick customer and patient access to CDT led breakthroughs.