ERC FUNDED PROJECTS

The aim of this project is to understand the causal factors contributing to the cognitive decline during senescence and to develop sensitive and standardized behaviour tests for early detection in order to increase the welfare of affected species. With the rapidly ageing population of Europe, related research is a priority in the European Union. We will focus both on characterising the ageing phenotype and the underlying biological processes in dogs as a well-established natural animal model. We develop a reliable and valid test battery applying innovative multidisciplinary methods (e.g. eye-tracking, motion path analysis, identification of behaviour using inertial sensors, EEG, fMRI, candidate gene, and epigenetics) in both longitudinal and cross-sectional studies. We expect to reveal specific environmental risk factors which hasten ageing and also protective factors which may postpone it. We aim to provide objective criteria (behavioural, physiological and genetic biomarkers) to assess and predict the ageing trajectory for specific individual dogs. This would help veterinarians to recognise the symptoms early, and initiate necessary counter actions. This approach establishes the framework for answering the broad question that how we can extend the healthy life of ageing dogs which indirectly also contributes to the welfare of the owner and decreases veterinary expenses. The detailed description of the ageing phenotype may also facilitate the use of dogs as a natural model for human senescence, including the development and application of pharmaceutical interventions. We expect that our approach offers the scientific foundation to delay the onset of cognitive ageing in dog populations by 1-2 years, and also increase the proportion of dogs that enjoy healthy ageing.

1 202 500 €

Start date: 2016-06-01, End date: 2021-05-31

"FUEL-PATH aims at providing new knowledge on plant cell wall and innovative biotechnological solutions for biomass utilization. A key process for biomass utilization is the initial degradation of cell walls into fermentable sugars (saccharification); this is hindered by the wall recalcitrance to hydrolysis. We propose to improve the plant saccharification characteristics by mimicking a strategy successfully used by phytopathogenic microorganisms. These produce pectic enzymes before other cell wall-degrading enzymes (CWDEs) to weaken the linkages between the wall components and favour the maceration of the plant tissue. Homogalacturonan (HGA), a major component of pectin, is synthesized in a methylated form and is de-esterified in the wall by methylesterases (PMEs). De-esterified HGA interacts with calcium to form ""egg-box"" structures, which are critical for maintaining the integrity of the entire wall. We propose to improve saccharification by expression in plants of microbial polygalacturonases (PGs) hydrolizing HGA. Plants expressing a fungal PG have reduced levels of HGA and enhanced saccharification (unpublished preliminary data). Since PG activity in pianta affects normal growth, a technology of enzyme control through the use of specific protein inhibitors will be developed. A second strategy to be adopted for weakening the ""egg-box"" is the overexpression of PME inhibitors. This may cause not only an increased degradability but also an enhanced biomass production. FUEL-PATH will provide detailed information on the structure, function and construction of tailor-made enzymes and inhibitors suitable for the saccharification process. FUEL-PATH will also address the relationship between pectin composition and developmental responses mediated by hormones in PG-expressing plants. A genetic screen will be performed to isolate genes involved growth defects and increased cell wall degradability and these will be characterized for a possible biotechnological use."

2 099 600 €

Start date: 2009-01-01, End date: 2014-06-30

Fighting microbial infection of wounds, especially in immunocompromised patients, is a major challenge in the 21st century. The skin barrier is the primary defence against microbial (opportunistic) pathogens. When this barrier is breached even non-pathogenic fungi may cause devastating infections, most of which provoked by crossover fungi able to infect both plant and humans. Hence, diabetic patients (ca. 6.4% of the world population), who are prone to develop chronic non-healing wounds, constitute a major risk group. My research is driven by the vision of mimicking the functionality of plant polyesters to develop wound dressing biomaterials that combine antimicrobial and skin regeneration properties. Land plants have evolved through more than 400 million years, developing defence polyester barriers that limit pathogen adhesion and invasion. Biopolyesters are ubiquitous in plants and are the third most abundant plant polymer. The unique chemical composition of the plant polyester and its macromolecular assembly determines its physiological roles. This lipid-based polymer shows important similarities to the epidermal skin layer; hence it is an excellent candidate for a wound-dressing material. While evidences of their skin regeneration properties exist in cosmetics formulations and in traditional medicine, extracting polyesters from plants results in the loss of both native structure and inherent barrier properties hampering progress in this area. We have developed a biocompatible extraction method that preserves the plant polyester film forming abilities and their inherent biological properties. The ex-situ reconstituted polyester films display the native barrier properties, including potentially broad antimicrobial and anti-biofouling effect. This, combined with our established record in fungal biochemistry/genetics, places us in a unique position to push the development of plant polyester materials to be applied in wounds, in particular diabetic chronic wounds.

1 795 968 €

Start date: 2015-09-01, End date: 2020-08-31

"The analysis of variation in plants has revealed that their genomes are characterised by high levels of structural variation, consisting of both smaller insertion/deletions, mostly due to recent insertions of transposable elements, and of larger insertion/deletion similar to those termed in humans Copy Number Variants (CNVs). These observations indicate that a single genome sequence might not reflect the entire genomic complement of a species, and prompted us to introduce the concept of the plant pan-genome, including core genomic features common to all individuals and a Dispensable Genome (DG) composed of partially shared and/or non shared DNA sequence elements. The very active transposable element systems present in many plant genomes may account for a large fraction of the DG. The mechanisms by which the CNV-like variants are generated and the direction of the mutational events are still unknown. Uncovering the intriguing nature of the DG, i.e. its composition, origin and function, represents a step forward towards an understanding of the processes generating genetic diversity and phenotypic variation. Additionally, since the DG clearly appears to be for the most part the youngest and most dynamic component of the pan genome, it is of great interest to understand whether it is a major contributor to the creation of new genetic variation in plant evolution and more specifically in the breeding process. We thus aim at: i) defining extent and composition of the pan genome in two plant species, maize and grapevine; ii) identifying the different mechanisms that generate and maintain the dispensable portion in these 2 species; iii) identifying the phenotypic effects of the DG; iv) estimating the rates and modes of creation of new genetic variation due to DG components and whether this could represent an important factor in the breeding process; v) extending our findings to other plant species for which the genome sequence in the meantime may have become available."

2 473 500 €

Start date: 2012-07-01, End date: 2017-12-31