The context of our research is the SGC pursuit of structures and chemical probes. We collaborate closely with the whole SGC, by providing and developing the high-throughput crystallography infrastructure required for crystallization and structure solution of SGC-produced proteins. Tens of proteins are moved into crystallization every week by our group and other SGC groups; the PX group enables and assists rapid optimization, diffraction screening, synchrotron data collection and structure solution: an ideal situation for methods development.
The PX group is a joint research effort with Diamond's beamline I04-1 and the XChem Fragment Screening Facility. XChem is extensively used within the SGC chemical probe pipeline to reveal drug target binding sites and provides starting point for chemical elaboration.
The scope of the group's research encompasses: generating and identifying soakable crystal systems, identifying weak fragment binders, quantifying binding affinity of fragments and elaborated compounds, developing protein scaffolds to enable rapid crystallization of challenging targets, software engineering for streamlined data analysis and algorithm development.
Tobias works as a Team Leader in the group since he joined in 2009. The main focus of his research is fragment-based lead discovery and crystallographic software development. Tobias studied Biotechnology at FH Weihenstephan (Germany) and trained as a structural biologist at the Max Planck Institute of Biochemistry in Martinsried (Germany). He received a PhD from Cardiff University in 2005 and afterwards worked as a postdoc at the Institute of Molecular Pathology in Vienna (Austria).
Having gained his B.Sc. in Biology and Statistics, from Oxford Brookes University, in 2002, Nathan worked at the Institute of Biotechnology (University of Cambridge, Chris Lowe Group). After working in publishing for Elsevier and Thompson Reuters, he joined the von Delft Group in 2009; notable projects include the development of the Crystal Shifter, a semi-automated protein crystal mounting robot (now commercialized by Oxford Lab Technologies Ltd). Nathan continues to research and develop engineered solutions to the experimental requirements of the SGC.
Beth obtained a BS in Electrical Engineering at the University of Illinois, specializing in computer logic design, and worked several years in CPU and system design for Data General Corporation. She obtained an MS in Biomedical Engineering from Boston University, with her thesis "A comparison of fixed and adjustable filterbanks for time-frequency processing". Before coming to SGC she worked at the University of Virginia, in the Department of Molecular Physiology and Biophysics, first in the Membrane protein structural biology lab of Professor Michael Weiner and then for Professor Wladek Minor. She also worked for crystallographic software company HKL Research, Inc. At SGC Beth is currently a laboratory engineer and is working in Protein Crystallography and Cryo-EM methods.
Following a PhD at imperial college Michael has done several post-docs in the field of protein engineering at various institutes. Michael works mostly on methods to obtain better diffracting protein crystals (surface mutations, fusions, optimised construct design). More recently he has started a collaboration with Precision Biosciences to obtain structures of their ARC-nuclease which is a key part of their gene editing platform.
Janine graduated from the University of Cambridge with an MSci in Natural Sciences (specialising in Chemistry) in 2015. Her Master’s project was completed in Professor Chris Abell’s group and concerned the development of inhibitors of M. tuberculosis using fragment-based drug discovery. Following a year studying chemical biology at Harvard University, she began her DPhil under the supervision of Professors Paul Brennan and Frank von Delft at the SGC. Her project uses the XChem high-throughput protein crystallography pipeline developed at Diamond and the SGC to develop inhibitors for GTPase/GEF complexes.
Mingda obtained his BSc in Tsinghua University in China. After finishing his Bachelor's degree, Mingda joined the PX group in October 2017 as a DPhil student. He is working on adapting binder scaffolds as protein chaperones for effective crystallization and good protein behaviour in cryoEM.
Mpho obtained her MSc in Biochemistry at the University of Johannesburg in South Africa. After completing her MSc, she joined the PX group as a DPhil student where she is working on in vivo evolution of protein binders for improving protein behaviour.
Yuliya studied chemistry (BSc and MSc) at the Technical University (TUM) in beautiful Munich, Bavaria. During this time, she also lived in Ireland and Sweden for study and research. After finishing her Master’s, Yuliya worked as a research assistant in a protein crystallography lab, before joining the automation team at Boehringer Ingelheim, Biberach, Germany. Yuliya then joined the PX group in October 2017 as a DPhil student. She is working on how to progress fragments hit into potent binders efficiently.
Mihaela studied Biochemistry and obtained her MBiochem from Oxford University. She is currently a DPhil student in the PX and RI groups, working on computational methods for fragment elaboration, with a specific interest in compound selectivity.
Conor is interested in using statistical and machine learning to robustly automate tasks in structure-based drugs discovery. Conor did a BSc in Mathematics with physics at the University of Southampton, Part III math at the university of Cambridge and is currently studying for a DPhil on the Systems Approaches to Structural Biology CDT program. Conor is supervised by Charlotte Deane and Frank von Delft of the University of Oxford and Gerard Bricogne of Global Phasing. He is part of the PX and OPIG groups. Conor is currently working on autofitting ligands into PanDDA event maps.
Lizbé completed her ungraduated studies in Chemistry at Stellenbosch University in South Africa, followed by an MSc in Chemical biology at the same institute. Needing a break from academia she joined Unilever SA as an evaluation technologist in the Homecare division, but returned 2 years later to do a PhD studying the mechanism of action and inhibition of the pantothenate kinases. In 2016 she joined the tuberculosis biology team at H3D, Africa’s first integrated drug discovery and development centre, to investigate and implement assays for drug characterization against various mycobacterial enzymatic targets. She has an interest in using structural approaches for target-based drug discovery and joined the team in February 2019 to expand on that skill set.
Alice is a Senior Beamline Scientist for the XChem platform on I04-1. She manages the XChem facility and the user support program. She studied Physics at the University Paris 7 (France) and completed a joint PhD (University Orsay, France and EMBL-Hamburg, Germany) in biophysical characterisation of protein interactions. Alice then moved to the pharmaceutical industry (Morphochem, Switzerland and Evotec Ltd, UK) where, as a crystallographer, she was involved in structure-based drug design projects, before joining Diamond in 2007 for the construction of I04-1 beamline.
Jose Brandao is the Senior Beamline Scientist with I04-1, responsible for its original design, construction and initial operations. He was in the Protein Structure Group at Astex Pharmaceuticals in Cambridge, UK, and prior to that he was a Beamline Scientist at the Protein Crystallography beamline with the Brazilian National Synchrotron Laboratory.
Louise joined i04-1 in November 2018, after completing her PhD in the Prischi Group at Essex University where she studied a cell survival pathway responsible for the development of chemo-resistance in Small Cell Lung Cancer. As part of her PhD she used the XChem facility at Diamond to screen hnRNP A1 as a novel drug target. Prior to this she worked for OncImmune Ltd (Nottingham, UK) producing commercially available ELISA-based blood tests for the early detection of various cancers, in particular developing high throughput methods for screening protein production buffers. Louise was awarded an MSc in Cancer Immunology and Biotechnology at Nottingham University and before that gained a BSc in Molecular Biology from Sheffield University. At present Louise is working on ways to increase the throughput of samples on i04-1 and is also investigating options for the new beamline in preparation for the Diamond II upgrade.
Anthony obtained his degree of Ingénieur Chimiste (CPE Lyon) and his Masters degree in Organic Synthesis and Chemistry of Bioactive Molecules (UCBL 1, Lyon) in 2009. His undergraduate studies included a year placement in Priaxon AG (Germany, Munich, 2008) and 6 months in an academic research lab (CO2GLYCO, ICBMS Lyon, 2009) on the synthesis of an oxa-analogue of FR901483 under the direction of Prof. Peter Goekjan and Dr. David Gueyrard. After graduation Anthony moved to Glasgow and started his PhD in the group of Prof. Stephen Clark, focused on the total synthesis of cornexistins. In August 2013 he joined the Marsden group as a postdoctoral researcher jointly supervised by Prof. Steve Marsden and Prof. Adam Nelson. He developed new routes to innovative libraries as part of the EU's €196M IMI project, the European Lead Factory. In Oxford since 2016, he has been involved in the seed project OxXChem aiming to increase the chemistry follow-up of early fragment hits obtained by the XChem HTS fragment screening platform and is now working as PDRA at Diamond Light Source.
Rachael completed her MChem in Chemistry with Research Experience in Bradford (2013), where she worked on multi-component co-crystals, investigating chaperoning the crystal packing of small organic molecules with alkali metals and crown-ethers through crystallography. Following this, during her PhD (St Andrews/CCDC) she worked on applying data from small molecule crystallography to solubility prediction. Rachael now works on all sorts of code for the XChem project, with a particular focus on automated pipelines for data curation, and follow-up chemistry.
Ailsa Powell is an Industrial Liaison Scientist responsible for supporting industrial clients using the XChem fragment screening facility at Diamond. With a background in macromolecular crystallography and protein biochemistry, she joined the Industrial Liaison Office at Diamond in 2018 after working in the biotech sector where she worked for a small company developing biological crystallographic techniques. Throughout her career, her main scientific focus has been using macromolecular crystallography for understanding drug targets as a foundation for drug discovery. She has worked with potential drug targets in the field of antimicrobials and antimalarials and has investigated the structural basis of antibiotic resistance in Gram negative bacteria. Following completion of her PhD from the University of Bristol she worked as a postdoctoral scientist at the Medical University of South Carolina and the University of Oxford before moving into biotech.
Alexandre Dias joined the Industrial Liaison Office at Diamond in 2011 and is mainly focusing on macromolecular crystallography activities. After a PhD in structural biology at Joseph Fourier University and a Master in management of innovation at Grenoble Business School, he worked within the Business Development team at PX’Therapeutics, in Grenoble, France.
Andrew completed his B.Sc. Hons in Biochemistry at the University of Adelaide, Australia in 2014. Following from this, he pursued a PhD in the laboratories of Professor Grant Booker and Dr John Bruning, using structural and biophysical techniques to investigate the ligand binding characteristics of a promising anti-tuberculosis drug target. Having submitted his thesis in December 2018, Andrew joined the PX lab as a post-doc in March 2019. Andrew took up a project centred around the fragment-based discovery against Alzheimer’s disease targets that is led by both Professors Paul Brennan and Frank von Delft.
After my secondary school in Brussels and a foundation year in the UK, I read Biochemistry and Genetics at the University of Nottingham. There, I discovered Structural Biology which led me to do a research project with Dr. Boyan Bonev on the expression and purification of C jejuni BamA membrane protein. Then, I went to Imperial College London to do a Masters in Structural Molecular Biology. My first project was with Prof. Michael Sternberg on computational protein-ligand docking and the second with Dr. Ernesto Cota on selective cell-free labeling of a toxic peptide for NMR spectroscopy. During my time at Imperial, I developed a strong and lasting interest in structure-based and computer-aided drug discovery. The following year I was awarded a full Wellcome Trust/ Diamond Light Source Scholarship at Oxford University in Structural Biology. After a rotation project during which I identified a number of fragment hits for a bromodomain target by X-ray crystallography, I am currently under the supervision of Prof Phil Bigging (Oxford University) and Prof Frank von Delft (Diamond Light Source) studying free energy calculation for fragment selection and elaboration. I am also a visiting student at the Sloan Kettering cancer research center in New York where I work on isothermal titration calorimetry of protein-fragment systems to validate my models with Prof. John Chodera.
Daren is a Beamline Scientist on the XChem Platform at Diamond. He joined the XChem team in February 2020 following 6 years in the Structural Biology group at the drug discovery company Evotec in Abingdon, where he was a frequent user of the platform.
He studied Medicinal Chemistry at the University of Glasgow before completing a PhD in structure-based design of protein kinase inhibitors with Professors Keith Jones and Richard Bayliss at the Institute of Cancer Research in London. Following his PhD studies, he spent 2 years as a PDRA in the Chemical Biology, Diagnostics and Therapeutics group at the University of Southampton working on the identification and validation of novel anti-bacterial drug targets.
Warren completed his PhD – CO2 photoreduction kinetics: an experimental and numerical approach – under the supervision of Prof. Mercedes Maroto-Valer. He has experience leading teams for the development of active pharmaceutical ingredient processes that include international collaborations with a technology transfer with Merck pharmaceuticals, process development for Cerbios-Pharma and a safety study for the Bill and Melinda Gates Foundation. Through academic and industrial experience, he has developed statistical and numerical expertise for scientiﬁc and engineering decision making. Warren recently joined the XChem group at Diamond Light Source. He will be working on developing user interfaces and making automated synthesis robotics accessible to chemists/non-chemists.