ERC FUNDED PROJECTS

Fish are the phylogenetically oldest vertebrate group with an immune system with clear similarities to the immune system of mammals. However, it is an actual matter of fact that the current knowledge of the fish immune system seems to lack the key piece to complete the puzzle. In 1953 Nelson described a new role of human red blood cells (RBCs) which would go beyond the simple transport of O2 to the tissues. This new role, involved in the defence against microbes, described the antibody and complement-dependent binding of microbial immune complexes to RBCs. Regardless of the importance of this finding in the field of microbial infection, this phenomenon has been poorly evaluated. Just recently, a set of biological processes relevant to immunity have been described in the RBCs of a diverse group of organisms, which include: pathogen recognition, pathogen binding and clearance and cytokines production. Furthermore, it has been demonstrated that nucleated erythrocytes from fish and avian species develop specific responses to different pathogen associated molecular patterns and produce soluble factors that modulate leukocyte activity. In the light of these pieces of evidences, and in an attempt to improve the knowledge of the immune mechanism(s) responsible for fish protection against viral infections, we raised the question: could nucleated fish erythrocytes be the key mediators of the antiviral responses? To answer this question we decided to focus our project on the evaluation of the crosstalk between red and white blood cells in the scenario of fish viral infections and prophylaxis. For that a working model composed of the rainbow trout and the viral haemorrhagic septicaemia virus (VHSV) was chosen, being the objectives of the project to evaluate: i) the implication trout RBCs (tRBCs) in the clearance of VHSV, and ii) the involvement of tRBCs in the blood transportation of the glycoprotein G of VHSV (GVHSV), the antigen encoded by the DNA vaccine.

1 823 250 €

Start date: 2015-04-01, End date: 2020-10-31

The mammalian cerebral cortex was subject to a dramatic expansion in surface area during evolution. This process is recapitulated during development and is accompanied by folding of the cortical sheet, which allows fitting a large cortical surface within a limited cranial volume. A loss of cortical folds is linked to severe intellectual impairment in humans, so cortical folding is believed to be crucial for brain function. However, developmental mechanisms responsible for cortical folding, and the influence of this on cortical function, remain largely unknown. The goal of this proposal is to understand the genetic and cellular mechanisms that control the developmental expansion and folding of the cerebral cortex, and what is the impact of these processes on its functional organization. Human studies have identified genes essential for the proper folding of the human cerebral cortex. Genetic manipulations in mice have unraveled specific functions for some of those genes in the development of the cerebral cortex. But because the mouse cerebral cortex does not fold naturally, the mechanisms of cortical expansion and folding in larger brains remain unknown. We will study these mechanisms on ferret, an ideal model with a naturally folded cerebral cortex. We will combine the advantages of ferrets with cell biology, genetics and next-generation transcriptomics, together with state-of-the-art in vivo, in vitro and in silico approaches, including in vivo imaging of functional columnar maps. The successful execution of this project will provide insights into developmental and genetic risk factors for anomalies in human cortical topology, and into mechanisms responsible for the early formation of cortical functional maps.

1 701 116 €

Start date: 2013-01-01, End date: 2018-06-30

In contrast to human or rodent embryos, ungulate embryos do not implant into the uterus right after blastocyst hatching. Before implantation, the hatched ungulate blastocyst must undergo dramatic morphological changes characterized by cell differentiation, proliferation and migration processes leading to the development of extra-embryonic membranes, the appearance of a flat embryonic disc and gastrulation. This prolonged preimplantation development is termed conceptus elongation and deficiencies on this process constitute the most frequent cause of reproductive failures in ungulates, including the 4 most relevant mammalian livestock species in Europe. The purpose of this project is to elucidate the factors involved in conceptus elongation by gene editing and in vitro culture approaches. A first objective will be to identify key genes involved in differentiation processes by RNA-seq analysis of different embryo derivatives from bovine conceptuses at different developmental stages. Subsequently, the function of some of the genes identified as well as others known to play a crucial role in mouse development or putatively involved in embryo-maternal interactions will be assessed. For this aim, bovine embryos in which a candidate gene has been ablated (KO) will be generated by CRISPR and transferred to recipient females to assess in vivo the function of such particular gene on conceptus development. A second set of experiments pursue the development of an in vitro system for conceptus elongation that would bypass the requirement for in vivo experiments. For this aim we will perform metabolomics and proteomics analyses of bovine uterine fluid at different stages and will use these data to rationally develop a culture system able to sustain conceptus development. The knowledge generated by this project will serve to develop strategies to enhance farming profitability by reducing embryonic loss and to understand Developmental Biology questions unanswered by the mouse model.

1 480 880 €

Start date: 2017-10-01, End date: 2022-09-30

This project studies the challenges that policy makers face in a world where globalization is proceeding at high speed and knowledge creation is the key to prosperity. It consists of two main parts: one focuses on optimal growth policies, the other on policy externalities induced by market integration. The first part builds on the premise that fostering innovation requires appropriate regulations on product market competition and on Intellectual Property Rights. The following questions will be addressed. What are the optimal competition and IPR policies when economic growth requires both innovation and technology diffusion? Are competition and IPR policies complements or substitutes? How does the optimal policy mix change with economic development? How do optimal contractual relationships evolve with development? What are the misallocations created by market power when sectors and firms are heterogeneous in technology and in the exposure to foreign competition? Are trade liberalization and competition policy complements or substitutes? The second part studies the consequences of and remedies to the growing mismatch between economic and political borders created by globalization. The following questions will be addressed: Why does the size of governments increase with globalization? Does higher international factor mobility lead to a race to the bottom in taxation? What is the effect of trade openness on pollution and environmental regulations? Can globalization induce governments to adopt more stringent environmental regulations? Does market integration call for a reorganization of the world political structure? Can the tendency to reinforce supra-national entities and the process of political fragmentation within states be complementary reactions to globalization?

450 000 €

Start date: 2009-09-01, End date: 2014-08-31