My research group is interested in developing novel biophysical tools for studying catalysis at metal centres within proteins. Of particular importance are enzymes that catalyse activation of small molecules such as dihydrogen (H2), carbon monoxide, carbon dioxide, and dinitrogen (N2). The chemistry that occurs at enzyme active sites is inspirational for production and use of future sustainable fuels. Active sites are often based around ‘inorganic’ cores similar to naturally-occurring minerals, and can be studied using a range of spectroscopic techniques. In combination with electrochemistry, it is possible to use spectroscopy to build up 'snapshots' of enzyme reactivity in situ during catalysis. At present we are involved in developing novel room-temperature methods for X-ray absorption spectroscopy, and time-resolved infrared spectroscopy. A deeper mechanistic understanding of how nature has developed efficient enzymes will provide inspiration for the next generation of biomimetic catalysts for green energy and synthesis. My research is supported by the Royal Society, Royal Society of Chemistry, Science and Technology Funding Council, Diamond Light Source, BBSRC, and EPSRC.
Dr Ash is the supervisor on the below project:
Secondary Supervisor(s): Dr Hannah Kwon
University of Registration: University of Leicester
BBSRC Research Themes:
Redox properties of metal-containing active sites are critically important to many biocatalytic processes: one third of all proteins contain a redox-active metal, and ca 22% of submissions to the Protein Data Bank contain a transition metal. Metalloproteins capable of extracting energy from H2 gas, sequestering CO2 from the atmosphere, or performing complex monooxygenation reactions, rely upon the ability to access and control a range of often exotic metal oxidation states in an aqueous environment. Much of this crucial chemistry occurs at extremely fast rates, making it challenging to study using conventional structural and spectroscopic methods.
This project aims to investigate the catalytic mechanisms and structural dynamics of metalloenzymes that are vital for chemical energy conversion, with a focus on hydrogenase. State-of-the-art spectroscopic and structural studies will be combined with computational analysis to reveal critical but elusive transient intermediates by studying reactions in real time on sub-microsecond timescales. The outcomes of this project will provide a step change in our understanding of the mechanism of hydrogenase and other metalloenzymes, and will serve as inspirational catalysts for future green energy technologies.
A PhD student will gain a broad range of interdisciplinary skills in spectroscopy, electrochemistry, chemical biology, structural biology, and biophysics whilst addressing critical questions about how nature achieves efficient chemical energy conversion.
- Molecular Biology (cloning & mutagenesis)
- Protein expression and purification
- X-ray Spectroscopy
- Time-resolved spectroscopy (infrared, Raman)
- Synchrotron science
- Chemical synthesis
- Enzyme kinetics
- Protein crystallisation
- Structure determination
Dr Ash is also the co-supervisor on a project with Dr Hanna Kwon.
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