This project has received funding from the
European Union’s Horizon 2020 Research and Innovation Program
under the Marie Skłodowska-Curie

Grant Agreement No. 637295

This cross-disciplinary Marie Curie Innovative Training Network builds upon the transformative opportunities created by existing X-ray sources and new sources soon to be operative in Europe.

These opportunities include using ultrafast X-ray sources to extract time-dependent structural information from proteins; and revolutionary possibilities created by X-ray Free Electron Laser radiation for an entirely new regime of pre-damage serial femtosecond crystallography.

No lag should exist between building new sources and training the next generation of scientists well versed in using these facilities.

Our research training will yield new scientific insights on fundamental properties of protein structure and dynamics: one of the most challenging problems in structural biology; and technological advancements in diverse fields from pharmacology to nanotechnology.

X-PROBE CREATES CLOSE INTERDISCIPLINARY COLLABORATION BETWEENSTRUCTURAL BIOLOGISTS, PHYSICAL CHEMISTS, BEAMLINE ENGINEERS, SOFTWARE DEVELOPERS, AND INDUSTRIAL PARTNERS.

Few fields of research have benefitted as significantly as structural biology from interdisciplinary synergies between lab-bench scale science on the one hand and large scale research infrastructure on the other. For almost four decades synchrotron radiation physicists, beamline engineers and protein crystallographers have cooperated to drive the field forwards.

The outcome has been a spectacular growth in the rate at which new protein structures are solved. The scientific output of this endeavour is illustrated by six Nobel Prizes in Chemistry (Michel, Deisenhofer, Huber 1988; Walker 1997; McKinnon 2003; Kornberg 2006; Steitz, Yonath, Ramakrishnan 2009, Kobilka 2012), whose breakthroughs derive from diffraction data collected using synchrotron radiation. It is of crucial relevance to underline that the use of synchrotron radiation for structure-based drug design has become mainstream within pharmaceutical industry.

Very close cooperation between traditionally separate fields of research continues to be absolutely essential at the very cutting edge of structural biology. These opportunities include the use of short-pulsed X-ray sources for extracting time-dependent structural information from proteins; and the revolutionary new possibilities created by X-ray Free Electron Lasers, which combine ultrafast X-ray pulses with high brilliance focussing capabilities to create an entirely new regime of pre-damage time-resolved serial femtosecond crystallography on unprecedented time-scales.

Exploitation of the new scientific opportunities created by the changing technical landscape requires close interdisciplinary collaboration between structural biologists, physical chemists, beamline engineers, software developers, and industrial partners.

X-probe presents a state-of-the-art scientific research and training programme that builds upon current and developing X-ray source technology so as to extract dynamical information on protein conformational changes from femtoseconds to seconds. Our scientific programme is based upon two complementary, interdisciplinary objectives:

  • Objective 1: Synchrotron based Studies of Protein Structural Dynamics.
  • Objective 2: X-ray Free Electron Laser based Studies of Protein Structural Dynamics.

WE BELIVE IN YOUNG RESEARCHERS

The rapidly changing state-of-the-art demands that young researchers are trained to meet these new experimental, technical and analysis challenges at the forefront of structural biology and photochemistry. X-probe’s interdisciplinary and intersectorial training network incorporates four leading European X-ray facilities (ESRF, MAXIV Laboratory, European XFEL, SwissFEL); three academic laboratories at the forefront developing X-ray tools to probe protein dynamics; and both large and small industrial partners.

Early Stage Researchers (ESRs) will contribute strongly to both objectives and, through networking, secondments and joint experiments, benefit from cross-fertilisation of scientific ideas and technical solutions. On the technical side, the advent of improved synchrotron beamlines and advanced detector and sample handling technologies, as well as the enormous potential of X-ray free electron lasers (X-FELs), lends X-probe great importance as both a mechanism for developing new measurement techniques and as a platform for training the young scientists who will apply these techniques throughout their scientific careers.

X-FELs represent a major step forward in source performance and will require new measurement philosophies and equipment. Advances in detector technology require increased capabilities for data transfer and storage and improved algorithms for the processing of terabyte data sets. These developments will place heavy demands on motivated and highly trained talent. The time is ripe for bringing young scientists into the loop.

X-probe will train the nucleus of a new community spread across Europe that widens the access and use of non-conventional methods to image the time-evolution of biological systems.

X-probe has explicit links to all of these large X-ray facilities and will thereby train the next generation of European scientists to exploit these facilities for new scientific opportunities.

THE PROJECTS

Time-resolved diffraction & WAXS studies of heme proteins

Professor Beatrice Vallone Group
Sapienza University of Rome (UROM), Italy

Time resolved dynamics studies of membrane proteins

Professor Richard Neutze Group
University of Gothenburg (UGOT), Sweden

Time-resolved crystallography and WAXS studies at synchrotron sources

Professor Michael Wulff Group
European Synchrotron Radiation Facility (ESRF) Grenoble, France

Ultrafast X-ray diffraction & WAXS infrastructure

Professor Jorgen Larsson Group
Lund University (ULUND), Sweden

Serial crystallography at XFELs & synchrotrons

Professor Henry Chapman Group
University of Hamburg (UHAM), Germany

Dynamical studies of protein carriers

Dr Alessandra Bonamore Group
Molecular Links Rome srl (MOLIROM), Italy

Time resolved studies of visual rhodopsin

Professor Gebhard F.X. Schertler Group
PSI: Paul Scherrer Institute (SwissFEL) Villigen Switzerland