Figure 1: The ID30B experimental end station at the ESRF.
Figure 2: METTL16 methyltransferase domain with a modelled tRNA. The N-terminal extension important for binding RNA is shown in red.
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, the tunable and variable focus MX beamline on ID30B (Figure 1), and 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 Diffraction Instrumentation 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 (Aleksandrova et al.); Autotaxin - an important lysophospholipase implicated in many pathological diseases; RNA writer proteins in collaboration with the Pillai group at the University of Geneva (Mendel et al.), 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 is currently shut down for the ESRF Extremely Brilliant Source upgrade and will reopen for user operation in August 2020. To harness the unique scientific potential available after the ESRF-EBS in 2020 we will contribute to the upgrade of several beamlines. These include the planned upgrades of the bioSAXS beamline on BM29 and the fully automated MX beamline on MASSIF-1, as well as the construction and commissioning of a new serial crystallography end station on ID29. To realize the new experiments possible post ESRF-EBS we will also work on the development of automated serial data collection and analyses methods. We hope all these combined efforts will have an impact on future challenging structural biology problems.
In the laboratory, we will continue our research on the Slit-Robo signaling 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.