McCarthy Team

Synchrotron Crystallography Team

The McCarthy team works on the operation, improvement, and automation of MX and bioSAXS beamlines, and studies protein involved in signalling and neuronal 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 co-responsible for the microfocus MX beamline on ID23-2, the fully automatic MX beamline on MASSIF-1/ID30A-1, and the tunable MX beamline on ID30B. We’re also developing a web based graphical user interface, BSXCuBE3, for the bioSAXS beamline at BM29. Further information on these facilities can be found on the EMBL Grenoble services webpage. In addition, we work in close collaboration with the Instrumentation team on the design and user aspects of new scientific instruments. We also actively contribute in the design and implementation of complex MX and bioSAXS experimental workflows for automated sample screening, data collection and analyses.

In the laboratory, we study proteins involved in neuronal development, particularly the Slit-Robo signalling complex; Autotaxin ─ an important lysophospholipase implicated in many pathological diseases; RNA writer proteins in collaboration with the Pillai group at the University of Geneva, phosphoryl transfer proteins, and proteins involved in the Toxoplasma gondii immune evasion in collaboration with Dr. Hakimi of Grenoble Medical University.

Future projects and goals

The ESRF resumed user operation in August 2020 after completion of the ESRF Extremely Brilliant Source upgrade. While significant instrument and software upgrades were completed on all ESRF-EMBL Joint Structural Biology Group Beamlines both MASSIF-1 and BM29 underwent major refurbishments in 2020. On MASSIF-1 a new MD2S diffractometer and FlexHCD sample changer were installed for increased sample throughput and a CrystalDirectTM harvester will soon be installed to allow direct sample delivery from crystallisation plates. On BM29 we will continue to develop BSXCuBE3 following the installation of a new sample exposure unit, sample changer and X-ray detector. The team is also actively involved in the construction and commissioning of the new serial synchrotron crystallography beamline on ID29 that is currently underway. To harness the unique scientific potential of the fourth generation ESRF-EBS X-ray beams for European structural biologists we will continue to develop web based user interfaces and more sophisticated automated data collection and analyses methods. We hope all these combined efforts will have an impact on future challenging structural biology projects.

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. We will also continue our studies on the mechanistic selection and activation of MAP (mitogen-activated protein) kinases by upstream MAPK kinases as well as their subversion by T. gondii. Lastly, we will continue our work on Autotaxin and RNA writers.

The MASSIF-1 experimental end station at the ESRF.
Crystal structure of the homodimeric human NUDT12 catalytic core bound to m7GTP and Cd2+.