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

Pancreatic cancer has the lowest survival rate Pancreatic cancer has the lowest survival rate of all cancers in Europe, the median survival time is only a few months due to the lack of test for early diagnosis, and no effective therapies for metastatic forms. Pancreatic Ductal Adenocarcinoma (PDAC), like prostate and hepatocellular cancers present a down regulation of zinc importers and low zinc content. Treatment with clioquinol, a zinc ionophore, to increase the amount of zinc in the tumor has shown to inhibit tumor growth. This project aims at creating new tool to better detect PDAC by Magnetic Resonance Imaging, and the evaluation of di zinc ionophore to elevate the content in zinc in the tumor environment. Using the same modular approach, a normal and a zinc responsive contrast agent targeted to the PDAC will be synthesized by conjugation of a peptidic sequence known to target the tumor bearing a Single Core Multimodal Imaging Platform for quantification, with a peptide functionalized with a normal or zinc responsive contrast agent. After careful characterizations in vitro and ex vivo, they will be used in mice implanted with orthoptic pancreatic tumors. One of the projects developed by the “Metallic complexes for MRI” group, consist designing and using MRI probe for various substrates, including zinc. The group masters all the techniques to characterize the contrast agents, and the experience researcher (ER) will bring the knowledge about zinc biology, and infrared microscopy to quantify the contrast agent in tissues. Benefiting from the competitive interdisciplinary environment of CBM, and within the group, the ER will acquire new technical skills, knowledge and network the frontier between chemistry, biology and MRI imaging, in particular working with animal model (mice), to adequately implement the project and complete her skill set to become an independent researcher interested in developing tools to study the role of metals in biological context.

Mots clés : mri zinc responsive probe, peptide, pdac

Participants :
- Centre national de la recherche scientifique (France) — Coordinator, beneficiary, Recherche, subvention : 196707.84 €
Projet PANC561 (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Pancreatic cancer is a highly aggressive type of cancer, with poor prognosis and few effective therapeutic options. At the time of diagnosis only 20% of patients are eligible for surgery, the development of metastasis has already occurred. The life expectancy of these patients is 6-11 months (stage3) or 2-6 months (stage IV). Laminar Pharmaceuticals SL is pioneer in the development of bioactive molecules that act through modulation of the lipid composition of the cell membrane regulating key signaling pathways for different pathologies, including cancer. Recently, Laminar Pharma has demonstrated the high safety and promising efficacy of its most advanced drug in clinical development, LAM561 which is being developed for the treatment of glioblastoma. The clinical study phase IIb/III of LAMP561 in glioblastoma, which evaluates the pharmacological safety of LP561 in combination with the standard treatment for this disease, is currently being completed, without observed severe adverse effects attributable to LAM561. The current project aims to carry out a preclinical study to evaluate the efficacy and safety of the anti-tumor drug LAM561 in cell and animal models of pancreatic cancer as monotherapy or in combination with standard chemotherapeutics. In addition, the study of cell migration in cell and animal models of pancreatic cancer may allow to explore the antimetastatic effect of LP561 pancreatic cancer, opening a new line of development in the company. This project aims to expand the product indications by including data on its safety and efficacy in the treatment of pancreatic cancer which requires urgent solutions. Therefore, the completion of the preclinical study would allow, at the end of the proposed studies, to launch human clinical trials to give pancreatic cancer patients the option of benefiting from this therapy more quickly. Furthermore, this represents a great opportunity which may foster the carrier of the current applicant researcher.

Mots clés : pancreatic cancer, membrane lipid therapy, sphingomyelin synthase, antimigratory activity

Participants :
- Laminar pharmaceuticals sa (Espagne) — Coordinator, beneficiary, Organismes privés (hors enseignement), subvention : 160932.48 €
Projet BNPGE (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Parent-of-origin effects are considered an important factor in the evolution and development of mammals and plants. Work on genomic imprinting has primarily focused on these two groups, yet reproduction in thousands of insect species involves an extreme form of imprinting known as “Paternal Genome Elimination”. In this case, males recognise, silence and, during sperm formation, discard the chromosomes they inherited from their father. Only the mother’s chromosomes are inherited from the males. The molecular mechanisms responsible for parental origin recognition and process of elimination during sperm formation remain largely unknown. To redress this, BNPGE aims at exploring a unique genomic system found in the mealybug Pseudococcus viburni: a “selfish” B chromosome that has acquired a way to escape from this genomic exclusion, therefore given itself the capability to be transmitted to the next generation regardless of parental origin. Using comparative transcriptomic and genomic analyses, as well as epigenetic approaches, BNPGE proposes to dissect molecularly how this B chromosome escapes from genomic exclusion. This system provides a rare chance to acquire novel insights into the epigenetic mechanisms underlying the recognition and exploitation of a chromosome’s parental origin, a widespread and evolutionarily conserved yet under-appreciated phenomenon. BNPGE will also add new knowledge of applied value as gene inactivation under genetic conflict has been implicated in a wide range of human diseases and disorders. Finally, BNPGE will equip the Fellow to become an independent researcher by enabling her to return and conduct long-term research in the EU, contribute to train and strengthen her research skills, expand her network of collaborators, produce high-impact publications, and enable research dissemination via conference communications and public outreach through the host institution and Internet media.

Mots clés : paternal genome elimination, reproductive systems, b chromosome, genomic conflict, selfish element, mealybug, epigenetics, heterochromatin

Participants :
- University of Edinburgh (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet PLPUK (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

Parental leave is a popular topic that has been the subject of much parliamentary debate, news articles and scholarly examination. The scholarship on parental leave has revealed that despite the stated intentions of policy-makers, parental leave has not always had positive impacts on women’s ability to return to the workforce and is not widely used by fathers, perpetuating the idea that mothers are best suited to the work of raising children. Given the importance of the work of child-raising, how can parental leave be organised in a way that benefits mothers, fathers, children and broader society? These questions can only be answered by the critical examination of existing policies, including its most recent changes, and interviews with parents’ use of leave. This examination must acknowledge the ways that gender, race and social class influence how such policies are developed and how parents use leave, particularly as policies and parents’ use of leave reflect widely held beliefs about what ‘good’ parenting looks like. Scholarship on parental leave has begun to address some of these questions, considering how parental leave impacts on breastfeeding rates, women’s working patterns and fathers’ involvement in childrearing but this scholarship has not done enough to critically consider how gender and race and class influence these factors. Unpicking the racial and class ideologies that shape socially constructed notions of ‘good’ parenthood, and ‘good’ motherhood, in particular, will help to shift the way we approach parental leave policy-making and perhaps other, related parenting policies. This work of considering race, gender and class is a necessary intervention in the study of parenting culture more broadly, which has not given sufficient attention to these ideas in analyses of ‘good’ parenting. This research will make an important contribution to this emerging field of parenting culture studies and to British policy-making in the field of parenting.

Mots clés : parental leave, parenting culture, intersectionality, black feminist theory

Participants :
- University of London (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 224933.76 €
Projet OptimisingIDS (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

Parents have direct access to one of the most effective child development tools - their own infant-directed speech (IDS). Access to rich linguistic input allows infants to develop language abilities in a rapid and effortless manner in their first years of life. These basic language skills are essential for efficient and effective acquisition of literacy skills and knowledge in all other academic areas when children start early formal education. However, not all children acquire these basic language skills to the same extent, giving some children a significant advantage even before they start school and leaving many others behind. Understanding how the early language environment can impact and enhance early learning language processes can inform not only the strategies for closing this gap in language ability, but the strategies to prevent it from emerging in the first place. This fellowship specifically focuses on investigating the language input of bilingual infants during their first 12 months of life, and it comprises two parts. Part 1 will identify the individual acoustic and linguistic components present in natural parental IDS. Detailed acoustic and linguistic analyses of natural speech recordings will be conducted. Part 2 will systematically measure the role of each individual component of IDS in facilitating infants’ performance in language processing tasks. Behavioural and neurophysiological measures of infants’ language processing (native speech perception, continuous speech segmentation, and neural entrainment to the speech signal) will be conducted. This project is the first to implement a combined analytical and experimental approach to the study of early linguistic input. The findings of this fellowship will allow us to identify the components of IDS critical to enhance language development and provide infants with the optimal type of linguistic input to achieve their maximum potential in the development of early language skills.

Mots clés : infant directed speech, linguistic input, infancy, language, vocabulary, language acquisition, bilingualism, speech perception

Participants :
- Basque Center on Cognition, Brain and Language (Espagne) — Coordinator, beneficiary, Recherche, subvention : 158121.6 €
Projet PROPHETIC (Horizon 2020, appel à projets 2014)
Action : Staff Exchanges
Panel : Information Science and Engineering
Statut du projet : CLOSED

Parkinson's disease (PD) is a movement disorder characterized by muscle rigidity, tremor, physical movement slowing and in extreme cases, loss of physical movement. Primary symptoms result of decreased motor cortex stimulation caused by insufficient dopamine formation in the brain’s dopaminergic neurons. Secondary symptoms include high level cognitive dysfunctions and subtle language problems. PD is chronic and progressive. Currently there is no cure for PD and associated costs, in terms of quality of life and health and social care expenditures, are expected to rise as the population ages. As none of the existing PD interventions has been really effective the field shows potential for the development of systems to monitor individuals and facilitate symptoms’ management. The design of efficient ICT management system integrating remote monitoring of multi-parametric factors, decision support for medical staff, personalized and adaptable care, and patient and family education is a viable solution. PROPHETIC will exploit modern smart miniaturized systems and advanced information systems towards an infrastructure for remote, continuous, noninvasive acquisition and advanced processing of multi-parametric data and friendly telecare provision based on serious gaming. It will use embedded electronics (suite and cap) capable of measuring neural, psychological, physiological, and biomechanical parameters, and securely communicating them to a Medical Business Intelligence System where pre-processed data will be further analysed hence overcoming real time activity monitoring limitations. Continuous monitoring while aware of the patient’s levodopa medication will help determine health and motor status and avoid levodopa side effects e.g. dyskinesia, freezing, low blood pressure, and falls. It will support caregivers’ decisions and allow early interventions. Appropriate information could be shared between the actors through e.g. smart phones with access according to their role.

Mots clés : parkinson disease, remote management, personal healthcar service, serious gaming

Participants :
- Aiju (Espagne) — Partner, beneficiary, Recherche, subvention : 108000.0 €
- Institute of Communication and Computer Systems (Grèce) — Coordinator, beneficiary, Recherche, subvention : 162000.0 €
- Stream vision (France) — Partner, beneficiary, Organismes privés (hors enseignement), subvention : 108000.0 €
- Université d'Orléans (France) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 162000.0 €
- Brainstorm (Spain) (Espagne) — Partner, beneficiary, Organismes privés (hors enseignement), subvention : 108000.0 €
Projet BMPARK (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Parkinson’s Disease (PD) is a progressive neurodegenerative disease. PD affects more than 6 million people worldwide while 1.2 million people have PD in Europe. For the European economy PD has a total socioeconomic cost of €13.9 billion per annum. With the aging demographic the number of individuals affects by PD are projected to double by 2030 highlight the need for disease modifying therapies. The neuropathological hallmarks of PD are the progressive loss of dopaminergic neurons in a region of the brain known as the substantia nigra in the midbrain, and the accumulation of intraneuronal inclusions called Lewy bodies and lewy neurite that consist predominantly of a protein called α-synuclein. Despite over half a century of investigation, there is no disease modifying therapy for PD. I propose that a protein called bone morphogenetic protein (BMP)2 can protect midbrain dopaminergic neurons in the PD brain. BMP2 is distinct from other neurotrophic factors used in the clinical trials to date in that it has a different signalling mechanism that can be targeted to protect dopaminergic neurons. Here I will assess the neuroprotective efficacy of viral vectors carrying the BMP2 transgene in the rat α-synuclein model of PD. I will determine if this molecular therapy can protect dopamine neurons and their axons against α-synuclein induced degeneration to maintain brain dopamine levels and improve motor function. To do this, I will use a multidisciplinary approach which will be paralleled by intensive training and career development opportunities to enable me to make a transformative contribution to knowledge and to achieve professional maturity and independence. In this way, this work has direct relevance for the future development of neurotrophic factors for clinical use in PD and the extensive dissemination and communication plans to target all stakeholders will ensure both societal and scientific impact in an European context and also for individuals with PD.

Mots clés : neurotrophic factors, parkinson s disease, alpha synuclein, neurite growth, bone morphogenetic protein

Participants :
- National University of Ireland (Irlande) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 184590.72 €
Projet HT4PD (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Parkinson’s Disease (PD) is caused by dopaminergic neuron loss resulting in motor symptoms that are treated with L-DOPA. However, ≤90% of patients develop involuntary movements, termed L-DOPA induced dyskinesia (LID). Another less well studied, but highly occurring PD symptom is depression. There is evidence that the serotonin system is implicated in both, LID and PD-linked depression. Serotonergic (5-HT) neurons uncontrollably release L-DOPA-derived dopamine, and HTR1a/b agonists counteract such release and LIDs. Serotonin re-uptake inhibitors (SSRIs) also attenuate LID, through a still unknown mechanism. The striatally enriched Gαs-coupled receptor, HTR4, has the potential to enhance excitability of spiny projection neurons, to affect the balance of striatal pathways that is disrupted in PD and is a candidate to modulate LID and PD-depression. D2 agonists reduce depressive behavior in PD models, pointing towards a role for the striatum. Specifically, the dorsolateral striatum shows diminished metabolism, in contrast to non-PD-depression where the ventral striatum is a substrate. HTR4 in cortex and hippocampus was linked to antidepressant action. Agonists and overexpression yield anti-depressant-like responses, however, striatal HTR4 in PD-depression has not been examined. 1. We will determine HTR4 protein expression on a cellular level (dSPNs, iSPNs) in transgenic mice. We will virally overexpress, knockdown and pharmacologically manipulate HTR4 and assess striatally-driven behaviors. 2. We will probe HTR4 in motor symptoms by altering expression/activity in unilaterally 6-OHDA lesioned mice. We will evaluate LID onset/severity, dyskinesia markers and LTP, depotentiation and LTD. 3. We will test bilaterally-lesioned mice with altered HTR4 expression/activity in depression/anxiety paradigms. We will determine the effect on the action of D2, HTR1a agonists and SSRIs. Our comprehensive investigation of HTR4 will lead to a new understanding and treatment of PD.

Mots clés : dopamine, serotonin, htr4, striatum, basal ganglia

Participants :
- Institut national de la santé et de la recherche médicale (France) — Coordinator, beneficiary, Recherche, subvention : 295061.76 €
Projet ROSNPD (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Parkinson’s disease (PD) is characterized by striatal dopamine (DA) depletion due to loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc).Understanding the mechanisms underlying the onset and progression of SNpc damage is a primary unmet goal in PD research.Cell loss occurs earliest and foremost in the ventro-lateral region of the SNpc.Previous work defines anatomical factors determining the vulnerability of the ventro-lateral SNpc:their large axonal arborisations,bursting activity with high Ca++ inflow,high oxidative stress and sensitivity to aging.However, all of these features are shared by SNpc neurons but neurodegeneration in PD begins specifically by the ventro-lateral tier. This DA depletion first occurs in the posterior striatum, which is involved and required for habit formation and routine behaviour.Indeed, the earliest motor features of PD are commonly associated with impairment of automatic movements.The striatum is well known to be engaged in learning and habit formation,a process that is DA dependent.Striatal DA is released phasically (SNpc firing related) triggered by emotional responses,whereas tonic dopaminergic modulation (non-SNpc firing related),predominates in routine behaviour. The precise mechanism whereby DA regulates the learning of a routine is not well defined but SNpc dopaminergic neurons are engaged in behavioural tasks showing an activation of their firing rate at the start of an instrumental task. This provides support to the notion that DA signals the onset/offset of a task and perhaps switching between tasks.In addition, they have a higher response to external stimuli (alertness, sensory) and to emotional behaviours (i.e. reward, salience). It is hypothesized here that in order to control the whole spectrum of a task, from goal directed to habitual, the ventro-lateral SNpc neurons are under higher functional demand, and the consequent metabolic overload makes them more susceptible to degeneration.

Mots clés : parkinson s disease, routine behaviour, habitual, dopamine, goal directed, substantia nigra, electrophisiology, optogenetics, calcium imaging

Participants :
- HM Hospitales (Espagne) — Coordinator, beneficiary, Recherche, subvention : 170121.6 €
Projet RECOLOR (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder, currently incurable. Studies in the PD field show that leucine-rich repeat kinase 2 (LRRK2) is both a major player in PD pathogenesis and a promising PD therapeutic target. LRRK2 functions in health and disease are not defined; however the applicant and others have shown that LRRK2 phosphorylation is the key to understanding LRRK2 biology. This project’s goal is therefore to understand the role of LRRK2 phosphorylation in PD by pursuing 3 specific aims: 1) elucidate the regulation of LRRK2 phosphorylation by phosphatases, 2) determine LRRK2 phosphorylation downstream phenotypes in cellular models through transcriptome profiling, protein translation profiling and protein tau related phenotypes, and 3) verify these findings from experimental models in PD biosamples. The project builds on the applicant’s extensive expertise in the field of LRRK2 biology (24 papers in 8 years) required for aim 1 and will leverage expertise on PD biosample analysis of the host institution (training for aims 2 and 3). The research program will be performed at the JPA research center (a mixed Inserm-Lille 2 University-Lille University Hospital center for excellence research, Lille, France), with a network of strategically chosen collaborating research groups locally and internationally, coordinated by the applicant. The study of LRRK2 phosphorylation in experimental models and translation of experimental results to clinical samples will reveal the most relevant molecular mechanisms of LRRK2 in PD which can be exploited in follow up work as diagnostic biomarkers and targeted for disease-modifying therapy. Given the importance of PD and neurodegeneration in Europe, this project is fertile ground for a high visibility fellowship and will reposition the applicant in the international neurodegenerative diseases research community by adding a clinical translation dimension to his signalling neurobiologist profile.


Participants :
- Université de Lille (France) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 185076.0 €