About Us
Diamond Light Source is the UK’s national synchrotron science facility. By accelerating electrons to near light-speed, Diamond generates brilliant beams of light from infra-red to X-rays which are used for academic and industry research and development across a range of scientific disciplines including structural biology, physics, chemistry, materials science, engineering, earth and environmental sciences.
The Project
This is a collaborative project between Keele University and Diamond Light Source, the UK’s national synchrotron science facility located at the Harwell Science and Innovation Campus. The project will use a variety of techniques in structural biology, including x-ray crystallography and cryo-electron microscopy (cryoEM), at both Keele and Harwell to characterise structurally the interactions and effector mechanisms of the innate immune proteins, human C-reactive protein (CRP) and complement component C1q.
The innate immune molecule CRP and the complement system play key roles in infection and inflammation. There is much biological and medical interest in their role including how they relate to inflammatory processes including cardiovascular and autoimmune diseases. More recently, CRP has been shown to be a very sensitive and useful marker in Covid-19 disease activity, extent and severity. As an acute phase reactant, CRP is activated by binding to phosphocholine residues on the surface of damaged cells or microbial and viral pathogens. Once bound a pathogenic ligand, CRP then activates complement via C1q and the classical complement pathway and exerts its pathogenic effects in human diseases. If we are to understand the CRP effector mechanisms, it is vital to structurally characterise the interactions of this protein with its physiological binding partners.
This multidisciplinary project will focus on the use of x-ray crystallography and cryoEM to characterise the interactions between CRP, its prototypical physiological target cell wall pneumococcal C polysaccharide and complement component C1q, using both intact and various fragments of these proteins. Initially, the successful applicant will be based at Keele University, a dynamic academic environment, under the supervision of Dr Annette Shrive in the School of Life Sciences. There the student will gain initial training and experience in the preparation and handling of these complexes and in crystallisation and x-ray data collection techniques. The student will then be based at the Harwell campus using a range of state-of-art facilities to determine the structure of these complexes with data collection at Diamond Light Source and the Electron Bio-Imaging Centre providing an ideal environment to study and learn with scientists from different disciplines. In parallel, at the Research Complex at Harwell crystallisation facility, the student will develop a workflow for cross-seeding approaches from different organisms or different fragments or ligands to generate different crystal forms and space groups as well as optimise crystal growth for size and homogeneity. At Diamond Light Source and the Research Complex at Harwell the student will have access to a huge range of cutting-edge instruments, including many not available elsewhere, with dedicated staff on hand to support their experiments. The project will conclude with dedicated structural analysis along with write up of manuscripts and thesis which will be completed at Keele.
For any further information or for an informal chat about the project please contact: Dr Annette Shrive a.k.shrive@keele.ac.uk or Dr Halina Mikolajek halina.mikolajek@diamond.ac.uk
Further Information
Diamond Light Source Ltd holds an Athena SWAN Bronze Award, demonstrating their commitment to provide equal opportunities and to advance the representation of women in STEM/M subjects: science, technology, engineering, mathematics and medicine.
Diamond jointly funds around 15-20 studentships every year with a variety of collaborators from both academic institutions to industry partners. Students accepted onto these projects will be part of our yearly cohort intake and are supported by both their academic and Diamond supervisors, as well as a dedicated Student Engagement team based at Diamond.
Diamond studentships are typically 50% funded by Diamond and 50% by the partnering university institution (or 25% funded by Diamond if there is a third party collaborator). Students are therefore required to spend 50% of their studentship at Diamond, with most students relocating to the local area for this period. Support on suggested accomodation options are provided by Diamond.
Benefits of Diamond's jointly funded studentships
Further Information
If you have further questions please contact the Student Engagement team on diamond.students@diamond.ac.uk.
Further guidance for students can be found here as well as more information about life at Diamond found here.
Closing date is 14 April 2023.
For any further information or for an informal chat about the project please contact: Dr Annette Shrive a.k.shrive@keele.ac.uk or Dr Halina Mikolajek halina.mikolajek@diamond.ac.uk
Diamond Light Source is the UK's national synchrotron science facility, located at the Harwell Science and Innovation Campus in Oxfordshire.
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