Protein crystallography has been used to determine almost 200,000 of the structures deposited in the protein data bank. Many of these are from crystals of purified proteins that measure up to hundreds of microns in size. However, not all crystals grow to a large size (>30 μm). Often, structural biologists will spend many weeks, months and years attempting to grow larger crystals with the hope that they produce better diffraction, which will lead to the determination of the molecular structure of the protein.
Synchrotrons provide the brightest, most uniform and smallest X-ray beams, which over time have enabled the collection of X-ray diffraction data from ever smaller crystals. This has relieved the efforts of the structural biologist in producing larger crystals. The technological progress and development of X-ray diffraction beamlines has led to the recently opened Versatile Macromolecular Crystallography microfocus beamline (VMXm). VMXm is a unique protein crystallography (MX) beamline, providing the smallest hard X-ray beam at Diamond for MX, as well as a unique sample position designed with the aim of capturing the naturally weak signals generated by microcrystals. The diffraction of crystals less than 10 μm can be recorded at VMXm and we have so far determined novel structures of samples that measure just ~3 μm across. However, VMXm has been designed with the aim of recording X-ray diffraction with submicron dimensions.
This summer placement project will work to characterise the minimum thickness of a crystal that can be used to collect high resolution data using the VMXm beamline. It will involve the production of microcrystals and preparing them with techniques borrowed from cryo electron microscopy such as plunge freezing. The crystals, now frozen at liquid nitrogen temperatures, will then be cut away to produce submicron thicknesses using a focused ion beam instrument coupled to a scanning electron microscope (FIB-SEM). The FIB uses a beam of charged ions to cut away material with very high precision. The student will then collect X-ray diffraction data from the milled crystals using the new VMXm beamline. Finally, the thickness of the milled crystals will be determined using both SEM and transmission electron microscopy at the electron bioimaging centre at Diamond.
The placement student will receive training in the use of these cutting-edge instruments, experience of scientific research and an opportunity to contribute to beamline development at Diamond.
The project will enable beamline scientists to open VMXm to ever smaller crystal samples, enabling more challenging biological structures to be determined with greater ease. It will also enable the current practical size limit of X-ray diffraction to be determined and compare this limit to the maximum size limit of current electron diffraction methods (~0.5 μm).
Applications are now closed for this project
Please apply via our online application portal. The vacancy that you are applying for is the "Summer Placements 2023" listing, you will then have the opportunity to select up to three projects to apply for. This project's reference is 23002SP.
Interviews will be scheduled for 6, 7, 8, and 9 February 2023.
If you are disabled and would like to be considered under the Disability Confident Scheme, please let us know via the online application process.
Please note that this role does not meet the required skill level for a Skilled Worker visa and therefore we would be unable to sponsor individuals due to the current UK Home Office immigration rules. To be appointed to the role, candidates will need to have the right to work in the UK without sponsorship from us.
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