Grenoble, Auvergne-Rhône-Alpes, France
My main roles will see me contribute to the technical development of the beamline, while providing user support as a local contact, providing advice and guidance on SAXS, experimental setup and data analysis for academia and for industrial users. I will also continue with my research and collaborations which I began at Diamond Light Source as well as starting new collaborations with select user groups.
Diamond Light Source is the UK’s national synchrotron science facility, located at the Harwell Science and Innovation Campus in Oxfordshire. I am attached to the small angle X-ray scattering (SAXS) beamline B21 where we specialise in biological solution scattering (BioSAXS). I am carrying out both development work of the technique and instrumentation on the beamline, and working on my own research projects as outlined below. The integration of SEC-SAXS One of the major problems faced during BioSAXS experiments is the monodispersity of the target protein. Even tiny amounts of impurities or protein aggregation caused from transport of sample can dramatically affect the quality of the scattering curves. The development of a high-performance liquid chromatography (HPLC) sample environment for solution scattering (SEC-SAXS) that couples the use of established biological separation techniques to the scattering experiment itself have helped resolve this issue. I recently upgraded the SEC-SAXS on B21 to a standard that should enable high throughput of samples both in terms of sampling and software. Glycosylated proteins The glycans present on the surface of proteins can vary greatly in size from being very minor in amount to being the dominant factor. There functions too are very diverse from structural scaffolding to signalling through glycan binding proteins. I am studying the relationship between the glycan and protein, utilising SAXS to determine the volumes of each glycan, and their spatial characteristics when bound to the protein. Radiation damage in SAXS Protein degradation through radiation damage is a common problem associated with SAXS beamlines. The main causative agent for this damage is thought to be the hydroxyl radical formed from the breakdown of water by the X-rays. I have investigating using different compounds to both limit the effects and to test whether the hydroxyl radical is the causative agent or not.
Investigating inhibitors to BACE I, the enzyme responsible for cleaving APP in neurons that leads to the formation of Lewy bodies in Alzheimer’s disease. BACE I is expressed using mammalian cell culture, inhibitors tested through activity assays and any structural deviations using SAXS and CD. Expressed and purified three enzymes that enable the cleavage of heparin, heparin sulphate and a further five enzymes that enable the modification of sulphation upon heparin. Taught Medical students problem based learning (PBL), supervised undergraduate project students and demonstrated basic scientific skills as well as biochemistry and molecular biology to undergraduates.
Designed and developed an immunoaffinity method to purify a new plasma derived therapeutic. As part of a small team, we took a plasma derived fibrant sealant from bench scale, through technical transfer and clinical trials.