Figure 1: The new ID30B experimental end station at the ESRF.

Figure 1: The new ID30B experimental end station at the ESRF.

Figure 2: Crystal structure of Exd1 from Bombyx mori.

Figure 2: Crystal structure of Exd1 from Bombyx mori.

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

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 small angle X-ray scattering (bioSAXS) beamlines. We are currently responsible for the microfocus MX beamline on ID23-2, the new automated MX service beamline on MASSIF-1/ID30A-1, the new tunable and variable focus MX beamline on ID30B (Figure 1), and the bioSAXS beamline at BM29. The team also manages the operation of BM14, which is run in partnership with the ESRF and the Indian government. Further information on these facilities can be found on the EMBL Grenoble services webpage. In addition, we work in close collaboration with the Diffraction Instrumentation and High-Throughput Crystallisation (HTX) teams on the implementation of new generation sample changers based on a 6-axis robot and in situ plate screening capabilities. We also actively contribute to the design and implementation of complex MX and bioSAXS experimental workflows for advanced sample screening and data collection, as well as contributing to the development and expansion of ISPyB, a database for MX and bioSAXS experiments.

In the laboratory, we study proteins involved in neuronal development, particularly the Slit-Robo signalling complex, proteins involved in piRNA biogenesis (Figure 2), and phosphoryl transfer proteins. Meanwhile, the BM14 group is actively involved in the structural studies of proteins involved in the Toxoplasma gondii epigenetic machinery in collaboration with Dr. Hakimi of Grenoble Medical University.

Future projects and goals

This year we will focus on expanding and optimising the capabilities of the new suite of MX beamlines on ID30A (MASSIF) and ID30B. On BM14 and ID30B, we will start to provide in situ screening and data collection capabilities for European users. We will also continue to develop methods and techniques with our ESRF and EMBL colleagues in order to optimise sample handling, and data collection and analyses functionalities. Lastly, ID23-2 will be upgraded to provide an intense 1 micron in diameter beamsize and equipped with a new high-precision diffractometer designed by the Instrumentation team. This beamline upgrade will provide an excellent test bench for the development of new instrumentation and methods in preparation for harnessing the unique scientific potential of the X-ray beam characteristics available after the ESRF Extremely Brilliant Source upgrade. We hope that all our combined efforts will have an impact on challenging structural biological problems.

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 extend work on human kinase signal cascades. The BM14 group will use in silico screening methods to identify and test new potential inhibitors of the Toxoplasma gondii epigenetic machinery.