The McCarthy team works on the design, construction and operation of MX and BioSAXS beamlines and studies proteins involved in neuron development.

Figure 1: Coffee beans contain large quantities of  beneficial compounds such as 5-CQA and 3,5-diCQA that  are predominantly synthesised by HQT and HCT respectively

Figure 1: BM14 in an in situ plate screening setup mode.

Previous and current research

The Synchrotron Crystallography Team works in close collaboration with the Structural Biology Group of the European Synchrotron Radiation Facility (ESRF) in the design, construction and operation of macromolecular crystallography (MX) and biological X-ray scattering (bioSAXS) beamlines. We are currently responsible for the microfocus MX beamline on ID23-2 and the bioSAXS beamline at BM29 as well as the commissioning of MASSIF-1 on ID30A and the new tuneable MX beamline on ID30B. The team also manages the operation of BM14, which is run as a partnership with the ESRF and the Indian government. The structural biology beamlines at the ESRF are currently undergoing an exciting transformation following the closure of the ID14 suite last year and the start of commissioning on ID30. On BM14, we are working in close collaboration with the Cipriani Team and are currently developing a new type of sample changer based on a 6-axis robot. We are also actively developing the use of workflows in the design and implementation of complex MX experiments for advanced sample screening and data collection.

In addition we study proteins involved in neuronal development, particularly the Slit- Robo signalling complex, and proteins involved in the synthesis of plant secondary metabolites. Meanwhile, the BM14 group is actively involved in the structural studies of proteins involved in the Toxoplasma gondii epigenetic machinery in collaboration with Mohamed-Ali Hakimi (Grenoble Medical University).

Future projects and goals

This year will be exciting with the completion of the next phase of the UPBL10 project with our ESRF colleagues, the first user operation of the new suite of MX-beamlines on ID30A (MASSIF) and ID30B. This ambitious project is part of the ESRF upgrade programme and will ensure that European users will have continued access to state-of-the-art structural biology beamlines for the next decade. On BM14, we will continue to develop a new sample changing robotic system and optimise the in situ screening of crystals in plates (see figure). We will continue to develop automated data screening, collection and analysis schemes, phasing methods using UV induced damage, and new workflow routines and display software using Eclipse-RCP technology as part of the DAWN and BioStruct-X collaborations respectively. We will further develop the highly automated BioSAXS beamline in collaboration with the ESRF, the Cipriani team and EMBL Hamburg, including the full integration of an online high-performance liquid chromatography system with additional biophysical characterisation features. We hope that our combined efforts will push the boundaries of structural biology to better understand how complex biological systems work at the molecular level.

In the laboratory we will continue our research on the Slit-Robo signalling complex by trying to decipher how exactly Slit activates Robo on the cell surface, and we will extend work on phosphoryl transfer into human kinase signal cascades. The BM14 group will over-express several Toxoplasma proteins in E. Coli to be structurally and biochemically characterised using the PSB facilities. Lastly, the initial work on a novel dequibiquitinase will be continued.