Research infrastructures (RIs) operate in complex innovation ecosystems where industry plays an increasingly important role. Pan-EU initiatives, such as the Innovation Union or the European Strategy Forum on Research Infrastructures, revolutionise the way public and private sectors work together, and help to create structural frameworks which are needed to foster such collaborations. While initiatives of this type play a crucial role in enabling industry to become a full partner of research infrastructures whether it is as a user, a supplier, or a co-creator, they do not fully utilise or engage Industrial Liaison and Contact Officers (ILOs/ICOs) which could have a central role in boosting the RI-industry partnerships. To address this gap, ENRIITC will build a permanent pan-European network of ILOs and ICOs. This will be done in a community-driven, cross-functional, cross-sectoral, multiplier-based way which will be inclusive and enable all interested parties to actively participate. By supporting the establishment of strategic, cross-border partnerships between industry and research infrastructures, ENRIITC will enable win-win results for all parties. With a timeline of 36 months, 11 partners from seven countries, and a strong support from 61 Associates from around Europe, ENRIITC will 1) establish a sustainable European network of ILOs and ICOs which enables mutual learning, 2) map collaboration potential between research infrastructures and industry, 3) develop and refine strategies and best practices to foster these collaborations, 4) raise awareness among industry for collaboration opportunities at research infrastructures, and demonstrate impact. The consortium and Associates will jointly balance the need for expertise from diverse scientific areas, combine it with practical insights from establishing relations with various industries operating in different sectors and geographical contexts, and propagate it among their networks.

1-Scientific background and objectives The control of the pH and metal homeostasis are two key factors in the survival of the human pathogen Helicobacter pylori in the gastric mucosa. The discovery of the link between this bacterium and gastric pathologies was awarded by the Nobel prize to B. Marshall and R. Warren in 2005. Understanding the link between the adaptability of H. pylori to the gastric environment, its resistance to acidity and its virulence is a great competitive challenge. It was found that, in H. pylori, the control of intracellular pH and that of the nickel and iron concentrations implies a unique and intricate regulatory network essential for its survival and colonization capacity (work by team 2 and others). Two metalloregulators, Fur (Ferric Uptake Regulator) and NikR (Nickel Regulator) are central in this regulatory network. Fur and NikR have been shown to control positively and negatively and in an interconnected manner the expression of several genes involved in metal homeostasis and in the response to acidity. The role and the mechanism of action of HpFur and HpNikR significantly differ from the regulatory processes already described in Escherichia coli. The aim of the present project is therefore to understand the specificities of the metalloregulators of H. pylori, in particular the mechanisms of direct transcriptional activation and their role in the relation between Ni(II) and Fe(II) homeostasis and the control of intracellular pH. This project involves three teams already collaborating on this topic and that were associated in recent publications. The strength of the project is that it is genuinely interdisciplinary with three teams using different approaches to answer the same biological questions. It comprises (i) microbiologists from the Institut Pasteur of Paris (H. de Reuse's group, team 2), who are experts in the study of H. pylori's virulence and in particular of the role of HpNikR in the response to acidity, (ii) the bioinorganic group of I. Michaud-Soret (coordinator, team 1), which is internationally recognized for their spectroscopic and mechanistic studies on E. coli Fur and (iii) structural biologists of L. Terradot's group (team 3) at the ESRF in Grenoble, who have recently solved the structure of HpNikR. 2- Description of project, methodology This project will investigate : i) the mechanisms by which Fur and NikR repress gene expression in response to metals and pH variations using the intergenic region nikR/exbB found to bind both regulators. ii) the mechanism of direct positive regulation by HpNikR using the promoter region of ureA encoding a structural subunit of urease, a major virulence factor of H. pylori. iii) the mechanism of direct positive regulation by HpFur using the fur promoter region. Three complementary approaches will be used: a) At the cellular level: team 2 will test in H. pylori functional predictions both for the metalloregulators (metal binding sites, pH effect) and for their DNA binding sites which will be generated by the structural approaches of the other teams. It will also explore in vivo the metal specificity of the NikR regulator. Techniques will include genetics, molecular biology (mutagenesis) and phenotypic analysis (in different growth or stress conditions). b) At a molecular level: team 1 will use quantitative analyses (Kd determination) on purified systems (proteins/DNA/metal). The approaches will include a combination of biochemistry techniques (chromatography and gels)) and biophysical techniques such as U.V.-visible, EPR and fluorescence spectroscopy (such as fluorescence anisotropy) at the equilibrium or resolved in time (using stopped-flow). The spectroscopic characterization of the metal bound to the proteins and protein/DNA complexes will also be performed. These experiments aim at defining the molecular basis of these regulations. c) At the atomic level: team 3 will perform resolution of three-dimensional structures by X-ray crystallography of the apo- and metalled- HpNikRs as well as the structures of HpNikR in complex with DNA operator sequences: nikR/exbB, ureA and nixA. The resolution of mutant structures will be performed and should enable us to investigate the importance of specific residues involved in the molecular sensing of metals and to decipher the intramolecular signaling mechanism. 3- Expected results This project should lead to a better understanding of the mechanisms of regulation by HpFur and HpNikR and give clues to the new direct positive action on these regulators. It will also bring new and original information on the metal- and pH-dependent cross-regulation of Fur and NikR and their role in the adaptability of this pathogen to the acidic environment of the gastric mucosa.

Advanced optical laser light sources and accelerator-based X-ray sources, as well as their technologies, scientific applications, and user communities, have developed independently over more than five decades. Driven by the developments at each optical laser and free-electron laser research infrastructures (RIs) in recent years, the gap between the optical laser and accelerator-driven light sources has diminished significantly. Both communities operate, implement, or plan advanced laser light source RIs, combining high-power optical and high-brightness X-ray light sources operated as dedicated user facilities. Operational and technical problems of these RIs have become very similar, if not identical. In specific cases, joint projects by the two communities have been initiated, but a closer and more structured collaboration of the corresponding communities and light sources is urgently required and shall be developed through this project. The present proposal for a European Cluster of Advanced Laser Light Sources (EUCALL) is the first attempt to create an all-embracing consortium of all (optical and X-ray) advanced laser light source RIs in Europe. Besides addressing the most urgent technical challenges, EUCALL will develop and implement cross-cutting services for photon-oriented ESFRI projects, will optimize the use of advanced laser light sources in Europe by efficient cross-community resource management, will enhance interoperability of the two types of light sources, will ensure global competitiveness, and will stimulate and support common long-term strategies and research policies for the application of laser-like short-wavelength radiation in science and innovation. The EUCALL consortium includes the three ESFRI projects ELI, European XFEL, and ESRF(up), several national RIs, and the LASERLAB-EUROPE and FELs OF EUROPE networks as representatives for the nationally operated optical laser and free-electron laser RIs.