Dynamic Structural Biology Studentship (stipend £2,000 above the standard UKRI rate)

Applications are invited for a studentship in dynamic structural biology starting in October 2020 to be jointly supervised by Dr Allen M. Orville (Diamond Light Source), and Professor Emma Raven (University of Bristol), and in collaboration with Professor Peter Moody (University of Leicester).

An outstanding frontier challenge in structural biology is to determine time-resolved structures at atomic resolution directly from systems engaged in catalysis, at physiological temperature and pressure. We and others hypothesize that most enzyme microcrystals (~2x2x2 μm3 and smaller) will equilibrate with substrate(s) in μs – ms, which is many times faster than the ~60 ms average enzyme turnover time in solution. We are targeting metalloenzyme catalysed activation of O2; a cornerstone of biology. The PhD studentship will visualise, in real time, the bond making and bond breaking events involved in heme- catalysed O2 activation with time-resolved serial crystallography methods at Diamond and at X-ray free electron laser (XFEL) facilities. In pursuing this ambitious goal, we will use many biophysical techniques that include time-resolved serial femtosecond crystallography (tr-SFX) combined with time- resolved X-ray emission spectroscopy (tr-XES) strategies to investigate reaction dynamics and structural characterisation of short-lived intermediates – ultimately producing a molecular movie of catalysis. The spectroscopic and crystallographic data will support electronic and atomic models of various species throughout reaction cycles, including Fe(III)-O-O- and Fe(IV)=O reactive species. These new serial crystallography methods allow us unprecedented opportunities to probe short lived intermediates at Diamond I24 and VMXi beamlines and at XFELs. Aspects of this PhD project will be carried out at the University of Bristol (School of Chemistry), Diamond Light Source (XFEL Hub at Diamond), and XFEL facilities around the world likely to include the LCLS in the USA, SACLA in Japan, PAL-XFEL in Korea, SwissFEL in Switzerland, and/or the European XFEL in Germany.

The project will involve training and use of the following methods: enzyme kinetics, various spectroscopies (uv-visible, EPR, resonance Raman), X-ray crystallography, and protein expression. No extensive prior experience of these methods is required, merely an ability and enthusiasm to apply chemical/biophysical principles to the study of metalloproteins.

The student will be registered at the University of Bristol and will join the Raven group, which is located in brand new laboratories in the School of Chemistry. The student will spend approximately 50% of their time working in Bristol and 50% in Harwell with the XFEL Hub at Diamond, as well as opportunities for data collection at one or more XFEL source. The successful candidate can expect to receive a wide-ranging, interdisciplinary training across these locations, and will be invited to participate in other external-facing activities (conferences, seminars) as part of the overall activities of the groups in this country and internationally.

How to Apply
Please make an online application for this project at http://www.bris.ac.uk/pg-howtoapply. Please select Chemistry (PhD) on the Programme Choice page. You will be prompted to enter details of the studentship in the Funding and Research Details sections of the form. Follow this link for more information on Diamond PhD studentships: https://www.diamond.ac.uk/Careers/Students/Studentships.html