Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet PeptiMOL (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Peptides have been acclaimed as the drugs of the future, thanks to their high specificity and activity, as well as their easy degradation. This implies that they generally possess reduced toxicity, few secondary effects, and are thus administered in small doses. Peptides possess multiple therapeutic applications, which include: antivirals, antifungals, antibiotics, modulators of the immune, cardiovascular and nervous systems, etc. However, it has been demonstrated that therapeutically relevant peptides generally exhibit limited capacity to diffuse across biomembranes such as the human gastrointestinal epithelium, in addition to their low stability. Moreover, due the short plasmatic half-life and low stability of these peptides, they are administered through injections, often several times a day. It is essential to develop methods for modeling the bioactivity of peptides, predict their pharmacokinetic profiles and ultimately allow for the design of novel peptide chains adapted to predetermined bioactivity profiles. Such modeling systems will allow for the design of peptides with favorable therapeutic efficacy, and above all, ensure their adequate bioavailability and (preferably oral) administration. Based on this background, the objectives of PeptiMOL are: • Define parameters (numerical molecular descriptors) for characterizing the structural, compositional and physicochemical properties of peptides and develop a user-friendly Java-based tool for their computation. • Construct mathematical models to predict the PK properties of peptides using the state of the art statistical and machine learning techniques. • Implement the developed models in a Java-based chemoinformatic platform which will enable potential end-users to virtually screen peptide libraries or design novel peptide structures with desirable physicochemical and PK profiles.

Mots clés : therapeutic peptides, quantitative structure pharmacokinetic relationships  qspkr, computational chemistry, pharmacokinetics, drug discovery

Participants :
- Moldrug ai systems sl (Espagne) — Coordinator, beneficiary, Organismes privés (hors enseignement), subvention : 160932.48 €
Projet AutismRigidPercept (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Perceptual and cognitive inflexibility is considered to underlie the repetitive and restricted behaviours of autism spectrum disorder (ASD). However, despite its severe effects on daily life of autistic individuals, the biological basis of these ASD core symptoms remain little known. In this project, I will investigate the neural mechanisms behind this fundamental mental inflexibility of ASD by examining neural activity during bistable perception, which is thought to be suitable for evaluation of such mental and perceptual rigidity. To detect neural responses from the brains of autistic individuals during such fluctuating perceptual experience, I will empirically calculate the energy landscape of brain activity from non-invasive measurements of brain activity and numerically simulate activity transition on the energy surface. Given the explanatory power of this method demonstrated by my preliminary data, this project is expected to provide the first empirical evidence for autistic impairments in dynamic brain activity that underlies the mental inflexibility of ASD. Furthermore, successful completion of this main project will provide insight for a novel non-invasive intervention protocol to mitigate such autistic cognitive rigidity, which will be subsequently tested within this research project. I believe that this project has the potential to provide a novel integrative perspective to understand autistic cognitive inflexibility and presents a promising approach to modify these relatively overlooked symptoms.

Mots clés : autism spectrum disorders, energy landscape, bistable perception, pairwise maximum entropy model, ising model, resting state brain activity, tdcs

Participants :
- University of London (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 195454.8 €
Projet VIBRiOD (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Periodontal disease, conditions that affect the structures surrounding the teeth, is the most common disease of mankind (listed #1 in 2001 Guinness World Records). The total economic impact of periodontal disease represents the major component of the $442 billion direct and indirect expenditures of oral diseases incurred worldwide in 2010. Periodontal disease can lead to tooth loss, causing aesthetic effect as well as affecting chewing and speech. Beyond oral health, it is associated with systemic diseases and even with cancer risk. Obviously, periodontitis represents a major global health problem with significant social and economic impact. Development of effective therapies, therefore, requires deeper insights into the etiopathogenesis of the periodontal disease. The focus has traditionally been that pathogenesis occurs when the balance between the oral microbial biofilm and the host is lost, owing to dysbiosis and immune overreaction of the host to microbial presence. However, bacterial-host interaction alone does not adequately explain the clinical features of the disease. Recently, a new paradigm was proposed in pathogenesis involving a viral and bacterial combination to promote long-term chronic inflammatory disease. The project VIBRiOD will be focused on the etiopathogenesis of periodontitis based on Epstein-Barr virus (EBV)–pathogenic bacterial biofilm–human immunity response synergies. Specifically, the VIBRiOD aims to understand 1) EBV behaviour during periodontitis and relationship to dysbiosis, 2) bidirectional interaction of dysbiosis and EBV activation, 3) tridirectional relationship of dysbiosis, EBV activation and host immune response. The multidisciplinary nature of the project is strong, involving a combination of classic to modern approaches of microbiology, molecular biology, immunology and virology. The results have the potential to contribute to the advancement of periodontitis research and ultimate control of the disease.

Mots clés : epstein barr virus  ebv, bacterial pathogens, periodontitis, ebv bacteria synergy

Participants :
- Université Côte d'Azur (France) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 196707.84 €
Projet PeripheRIS (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Economic Sciences
Statut du projet : SIGNED

PeripheRIS undertakes research to enable institutional support for innovation policy in European peripheries, with a focus on policy implementation. For more than a decade since the financial crisis, uneven development in Europe has intensified, while the economic, social and political problems faced by peripheral regions have become widely recognized. Yet, under the EU's regional and innovation policies, peripheries are meant to compete with core regions to be economically sustainable - a process which relies on innovation as a key driver of economic growth and prosperity. While it has been suggested for some time that institutions play a role in peripheral development, serious inquiry into institutional aspects of regional innovation systems (RIS) has only recently been sparked. PeripheRIS focuses on the interplay between institutions and actors for the innovation-driven, sustainable transition of peripheral regions in Europe, bridging institutional and entrepreneurial strands of RIS as they unfold in complex institutional-entrepreneurial relations. In peripheries, these can be reduced to key personalities on both sides, and the focus turns to the actors at work within the system. The research aims to uncover mechanisms of institutional support to innovation. From his placement at Eurac Research in Bolzano, Bradley Loewen will develop a case study on the innovation system of Italy's South Tyrol region for comparison to prior cases in Central and Eastern Europe. A mixed methods approach is adopted based on qualitative (interviews) and quantitative (causal process tracing) methods. The cases will support theory-building in the area of evolutionary economic geography, to overcome the need for deep contextualization in future case research, which is a limitation for policy learning. In addition to academic outputs, the project will result in a practical guidebook with recommendations to local and regional governments for supporting innovation in peripheries.

Mots clés : regional innovation systems  ris, institutions, systems and actors, peripheries, case study, varieties of capitalism, evolutionary economic geography, process tracing, mechanisms of change

Participants :
- European Academy of Bolzano (Italie) — Coordinator, beneficiary, Recherche, subvention : 183473.28 €
Projet CLIMB (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Permeability Assay (PAMPA) have limited biorelavance and can often be poorly predictive of of drug permeation, particularly for charged species and for complex membranes such as the BBB and particularly of membrane toxicity which remain key issue leading to high attrition rate and low productivity in the pharmaceutical industry. The proposed fellowship programme aims to address these issues in a very novel way by developing lipid bilayers supported on cutting-edge Plasmonically-Directed Nano-Structured porous arrays. The substrates prepared via a range of fabrication methods, including 2-photon 3D-nanoprinting, will allow for investigation of drug-membrane interactions, and permeability through a unique and novel principle, whereby the arrival time of single or few weakly- or non-fluorescent molecules at plasmonic volume in the nano-/micro-cavity is monitored via enhanced spectroscopic technique. Angle dependent Raman microscopy will permit study independently of the drug-membrane interactions and plasmonic hot spot so both structural and permeation times can be meausered and these studies will be carried out in parallel with Elelctrochemcial impendence spectroscopy of membrane integrity. This approach will dramatically advance the state-of-the-art in membrane assay. In parallel it provide high quality research training to the MRSA fellow along with, supported by the host institution training programme a range of career promoting transferable skills acquired. Leading the fellow to a fully-independent academic position.

Mots clés : spectroscopy, photophysics, biophysics, electrochemistry

Participants :
- Dublin City University (Irlande) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 175866.0 €
Projet PhytoPharm (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

Pharmacueticals in the agricultural environment pose a risk to the continued productivity of the crop producing industry. To gain a better understanding of the processes involved in plant exposure and bioavailability of pharmaceutical compounds, a systematic approach is proposed to characterize the mobility of a study compound from soil to pore water in twenty native soils selected to represent a broad range of soil chemical-physical properties. Characterization of resulting pore water conditions will be used to study the interactions between pore water and plants. Analytical methods will be utilized to determine mobility of the compound in soil, pore water, and plant tissue. Monitoring of 18 plant development endpoints will reveal phyto-toxicological risk associated with pharmaceutical exposure. These interactions will be used to construct and validate a landscape scale spatial model. Data gathered throughout this study as well as the resulting model will provide the first attempt at landscape scale analysis for terrestrial environmental risk assessment from emerging contaminants. Identifying potential risks will help insure the stability and productivity of the agricultural economy into the future. Further, the adaptability of the model to different geographic regions, outside England and Wales, allows for the emergence of research collaboration across the world.

Mots clés : emerging contaminants, phytotoxicology, antibiotics

Participants :
- University of York (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet EPIMAIZE (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Phenotypes are largely determined by genetic factors. However, a given genotype can give rise to very distinct phenotypes, as exemplified by the diversity of cell types in multicellular organisms. This phenotypic plasticity results from epigenetic changes; that is, reversible modifications to the DNA molecule and its associated proteins that modulate gene expression patterns. Epigenetic changes are critical to the establishment of developmental programs, but also to adjust transcription in response to the environment. The latter is particularly important for plant adaptation: owing to a sessile (immobile) lifestyle, plants cannot run away from adversity, and thus adapt to their environment by tuning gene expression in response to changing conditions. Most epigenetic information is erased from one generation to the next, so that new organisms start their life cycle with a “fresh” potential. However, there are instances in nature of heritable epigenetic marks that can be transmitted to the next generation. Thus, owing to their role in shaping gene expression, and the potential for heritable changes, epigenetic factors are of great interest for plant breeders, in their quest for adaptable, high yielding phenotypes. Most of our current understanding of epigenetic processes in plants has been developed in Arabidopsis, a key model system. However, the Arabidopsis epigenome is rather idiosyncratic, and this knowledge might translate poorly to crops. Here, we will use an interdisciplinary approach combining original genetic materials and bioinformatics to analyze epigenetic regulatory pathways in maize, with a focus on reproductive development. Maize is an important model plant, with a large and dynamic epigenome much more typical of crops. It is also a crop of great economic importance. Better understanding the epigenome of maize will open the door to the manipulation of key agronomic traits, including reproductive development, which is under strong epigenetic influence.

Mots clés : maize, reproductive biology, apomixis

Participants :
- Cold Spring Harbor Laboratory (Etats-Unis) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Institut de recherche pour le développement (France) — Coordinator, beneficiary, Recherche, subvention : 178603.2 €
Projet EpiSpec (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Phenotypic plasticity plays a key role at the onset of the speciation process, facilitating diversification though the induction of novel phenotypes in response to distinct environments. Via genetic accommodation and genetic assimilation, this influence may extend throughout the speciation process and beyond, into subsequent speciation events. While the epigenetic regulation of gene expression that mediates phenotypic plasticity has been extensively studied in lab-based model organisms, very little is known about epigenetic variation in natural populations. This project will be the first epigenetic study explicitly focused on the speciation process. Using cutting-edge techniques, the applicant will characterize DNA methylation variation within and among the sympatric species of a recently discovered endemic cichlid fish radiation in Lake Massoko, Tanzania. Specifically the applicant will test: if 1) newly formed species differ in the distributions of epigenetic marks across the genome, 2) genomic variants linked to phenotypic divergence among species are in genomic regions unusually high in DNA methylation, as expected under a hypothesis of epigenetic differences preceding fixed nucleotide differences during adaptive divergence, 3) genomic regions diverging in patterns of methylation among incipient species are also exhibiting high levels of methylation in populations of Astatotilapia calliptera, the ancestral, colonizing species. The results of this pioneering project will provide the first empirical evidence of the importance of epigenetic variation during the emergence of new species.


Participants :
- University of Bristol (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet ReversePlasticity (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

Phenotypic plasticity, the ability of a genotype to express distinct phenotypes in different environments, is assumed to facilitate individuals coping with new or rapidly changing environments. In the context of climate change, the phenotypic response to temperature has received particular attention since thermal plasticity is affecting the survival of populations and species distribution. Although temperature is an important variable that affects many traits, including gene expression, the genetic basis of phenotypic plasticity evolution remains poorly explored. This project aims at understanding what determines thermal reaction norms, i.e. how gene expression changes with temperature. Preliminary work in the host laboratory suggests that these reaction norms are modified during adaptation of Drosophila melanogaster populations evolving in a new fluctuating thermal environment. Yet, it is unclear whether these changes are the result of selection on phenotypic plasticity or if they are driven by direct selection on the trait value in the novel environments, as both effects are confounded. To detect adaptive change in phenotypic plasticity, we will use a reverse evolution experiment in which D. simulans populations first evolved in one of two different fluctuating thermal environments (hot and cold) and after one year were shifted to the other environment. We will analyse the gene expression profile of these populations at three successive time points during their evolution over a wide range of temperatures (from 15°C to 27°C). By changing the environment in the opposite direction, we will be able to distinguish between selection on plasticity and selection on the trait value, since the latter will not revert plasticity towards the initial state. Hence, we will distinguish adaptive and non-adaptive components of thermal plasticity of gene expression, and identify genetic pathways under selection for phenotypic plasticity.

Mots clés : experimental evolution, phenotypic plasticity, reaction norms, transcriptomics

Participants :
- University of Veterinary Medicine Vienna (Autriche) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 178156.8 €
Projet ALPINE (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Phosphoinositides (PIs) are minor components of cell membranes, and play important roles in cellular functions. In chemical synapses in mammalian brain, each PI distributes different subcellular areas in nerve terminals, and cooperate with many proteins to regulate synaptic transmission machinery. To understand how PIs regulate synaptic transmission, the ultrastructural distribution pattern and dynamics of PIs at nerve terminals are crucial because PIs may functionally interact with proteins at domains of nano-meter ranges called active zones (AZs) or peri-AZs. However, their ultrastructural distribution and dynamics in nerve terminals are poorly investigated because of some technical difficulties. This research project aims to investigate (1) the ultrastructural distribution of PIs at AZs and peri-AZs in nerve terminals, (2) co-localization of PIs with presynaptic proteins related to synaptic transmission, (3) the ultrastructural dynamics of PIs and PI-protein coupling during synaptic transmission, and (4) the physiological roles of PI-protein couplings in synaptic transmission, using electron microscopic and electrophysiological techniques combined with optogenetics and biochemical tools. These highly-interdisciplinary approaches will unveil the physiological roles of PIs and PI-protein couplings in synaptic transmission, and is expected to give a fundamental breakthrough in understanding mechanisms of synaptic transmission.

Mots clés : phosphoinositides, freeze fracture, synaptic transmission, immunoelectron microscopy, patch clamp, optogenetics

Participants :
- Institute of Science and Technology Austria (Autriche) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 178156.8 €