Research Groups

EMBL Grenoble is a key player in the Partnership for Structural Biology (PSB) which integrates the activities of several Grenoble institutes involved with structural biology and thus is able to provide a uniquely comprehensive range of platforms for both inhouse research and external users.

A cornerstone of the PSB (established with the Institut Laue Langevin (ILL), the Institut de Biologie Structurale and the European Synchrotron Radiation Facility (ESRF)) is the close interaction of EMBL Grenoble with ESRF, which involves collaboration on building and operating beamlines for macromolecular crystallography and small-angle scattering, developing the associated automated instrumentation and techniques, and providing expert help to external visitors. The highly automated ESRF crystallography beamlines are equipped with EMBL-designed high-precision micro-diffractometers and frozen crystal sample changers. One beamline is run in collaboration with India. A new X-ray small-angle scattering instrument built by ESRF and EMBL is now operational with a custom designed small-volume automatic sample changer.

High throughput methods have also been introduced in other steps of the structure determination process, a development closely connected with our involvement in several European-wide projects. These include a very successful robotic system for nanovolume crystallisation and a novel high throughput screening method, ESPRIT, which enables soluble protein domains to be identified in otherwise badly expressed or insoluble proteins. More recently, a Eukaryotic Expression Facility (EEF) has been established specialising in the expression of multi-subunit complexes in insect cells, building on and further developing the well known MultiBac method. All these platforms are now available to external users under the EU funded P-CUBE and BioStruct-X projects.

A strong tradition at the outstation is the study of systems involving protein-nucleic acid complexes and viruses. The structural work on aminoacyl-tRNA synthetases is particularly well-known and has recently focussed on elucidation of the mode of action of a novel boron-containing antibiotic, which targets leucyl-tRNA synthetase. Projects involving protein-RNA interactions also include cryo-EM studies of the signal recognition particle and holo-translocon, with the ribosome and other proteins and complexes involved in RNA processing, transport and degradation, such as the nonsense-mediated decay (NMD) pathway. The analysis of mechanisms of transcriptional regulation, including at the epigenetic level, is another important topic. Structural analysis of eukaryotic transcription factor and chromatin-modification complexes is continuing, with groups working on TFIID, p300, and the dosage compensation complex. One group is also working on the biology of micro-RNAs, in particular trying to understand the biogenesis and role of piRNAs, which are critical for silencing transposons in the germ line. Another major focus is the study of segmented RNA viruses, particularly influenza and bunyaviruses, with the aim of understanding how they replicate, and also as targets for anti-viral drug design. Recently, the first crystal structures of domains of the influenza virus polymerase have been determined, which depended on the prior identification of soluble fragments using the ESPRIT method. In addition there are two projects related to the pathway of activation of interferon in response to viral infection: one focussed on the viral RNA pattern recognition receptor RIG-I, and another on the downstream kinase TBK1. The CNRS-Grenoble University-EMBL Unit of Virus Host Cell Interactions (UVHCI) is situated in a building next to the outstation.

Scientists at EMBL Grenoble have access to a wide range of techniques, including molecular biology and biophysical techniques, cryo-electron microscopy, isotope labelling, NMR, neutron scattering, X-ray crystallography and small angle scattering. A confocal microscope with facilities for cross-correlation spectroscopy is available for the study of complex formation in cells, as well as a top-end Polara electron microscope with cryo-tomography capability.

Stephen Cusack
Head of EMBL Grenoble