Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Motiliy in the third domain of life: the haloarchaeal way to move (ARCHAEAL MOTILITY)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Germany,Germany
Call:  (FP7-PEOPLE-2013-IEF, 2013)
Start date: 2015-03-01
End date: 2017-08-02
Duration (months): 24.0
Total project cost (EUR): 161968.8
EU funding (EUR): 161968.8
Participants: 2
Project status: CLOSED

The first representatives of the third domain of life, Archaea, were isolated from particularly harsh environments. Long it was thought that all archaea are ‘extremophiles’, but recently archaea were discovered in many temperate habitats, including the human gut, sea and soil, where they perform key roles in biochemical cycles. Archaea are the least explored domain of life and little is known about the mechanisms underlying motility and adhesion. Understanding these processes is especially timely since the widespread occurrence of archaeal species in environments including the human body is becoming more and more apparent. Archaeal motility has initially been studied using a thermophilic model organism, which has revealed that the structure responsible for swimming behavior of archaea is the ‘archaellum’. The archaellum has structural homology with bacterial type IV pili, which are at the basis of the pathogenicity of many Gram negative bacteria. However, the archaellum is rotating and thereby functionally resembles the bacterial flagellum. Taking advantage of this initial expertise and knowledge on archaeal motility available in the host laboratory, this project aims to focus on the mesophilic euryarchaeal model: Haloferax volcanii. This model is very appealing to study the molecular mechanism underlying motility, because genes encoding the archaellum components are linked with those of the bacterial chemotaxis pathway in haloarchaea. In addition, this model is one of the few genetically tractable archaeal systems that allows for advanced engineering, offering the unique option to study the mechanism of rotational switching, which influences the cells ‘decision’ to move or stay. The proposed research is important from both fundamental and medical perspective. In addition it opens the exiting possibility to develop a stable minimal nano-motor for synthetic biology, because the archaellum represents the biological rotating filament with lowest complexity

Keywords: archaea,motility,nano-motor,swimming behavior,rotational switching,chemotaxis
The germline mutational landscape of chronic lymphocytic leukemia (CLLRISK)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Incoming Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Spain
Call:  (FP7-PEOPLE-2013-IIF, 2013)
Start date: 2014-03-01
End date: 2016-06-20
Duration (months): 24.0
Total project cost (EUR): 230036.6
EU funding (EUR): 230036.6
Participants: 1
Project status: CLOSED

Chronic lymphocytic leukemia (CLL) is a cancer of B-lymphocytes, which expands in the bone marrow, lymph nodes, spleen and blood. While many genes have been implicated in CLL development through sequencing the genome of tumor cells, they do not completely explain the pathogenesis of the disease, nor define the early events that lead the B-cells to proliferate and become cancerous, accumulating the different types of somatic mutations of CLL. Most sequencing studies have focused only on discovery of somatic mutations without investigating germline risk variants. The aim of this project is to identify the landscape of germline risk factors that can predispose an individual to CLL. We will utilize whole-genome and exome-sequencing data on 100 and 500 CLL cases (normal and tumor samples) respectively, from the Spanish CLL consortium (International Cancer Genome Consortium). We will identify recurrent predicted damaging germline mutations. The results from relevant genes will be replicated in a larger cohort of cases and controls. The 20 most important genes accumulating damaging germline mutations in CLL patients (preliminary results involve cell-cycle, DNA damage checkpoint, double-strand break repair genes) will be tested at the functional level to evaluate the nature of the biological processes that are enriched in CLL. We will either use Saccharomyces cerevisiae or cell lines as model systems for functional analyses of the selected genes. We will also then implement other systems, such as Caenorhabditis elegans or Danio rerio models, for which convergent data on mutations in the altered pathways have been obtained. We expect to identify the complete spectrum of susceptibility genes involved in the early stage of development of this type of leukemia and advance the understanding of its pathogenesis.

Keywords: chronic lymphocytic leukemia,germline mutations,single nucleotide variants,genetic risk,copy number variants,genome sequencing,cancer susceptibility genes,dna repair,cell-cycle,dna damage
Imaging Interneurons in Epilepsy (IMAGINE)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: France
Call:  (FP7-PEOPLE-2013-IEF, 2013)
Start date: 2015-09-01
End date: 2017-08-31
Duration (months): 24.0
Total project cost (EUR): 202405.8
EU funding (EUR): 202405.8
Participants: 1
Project status: CLOSED

Oscillations of the neuronal network are well defined in the hippocampus, with theta oscillations associated with numerous cognitive functions. The role interneurons play in hippocampal oscillations is also well defined; however, the rules governing cell type-specific firing during oscillations are not known. The goal of this study is to determine how afferent inputs are processed to produce a given output in one class of GABAergic interneurons: Hippocampus-Septum (HS) interneurons using combined three-dimensional two-photon, electrophysiological and histological/anatomical methodology.Our proposal involves groundbreaking research by studying oscillations in a complete hippocampal preparation both on the network and subcellular level. The methods and technology to be involved is above the state-of-the-art, as novel, rapid three-dimensional two-photon techniques will be applied in conjunction with multicellular and single cellular electrophysiology. The project means the continuation of a fresh collaboration using the Hungarian partner’s knowledge on two-photon single- and multicellular imaging parallel with the French partner’s basis in epilepsy and neuronal oscillations. In a 24 month undertaking, the following objectives are to be addressed: 1) Rules of action potential genesis and backpropagation in HS cells. 2) Active properties of dendrites in HS cells. 3) Rules of synaptic integration during physiological oscillations in HS cells. 4) Hyperexcitability and dendritic properties of HS cells. The combined results on imaging, electrophysiology, immunohistochemistry and methods for correlation will be applied to deduct the correct conclusions on how hippocampal oscillations affect single neurons, neuronal processes and dendritic phenomena. As a result, we will be able to gain new insight on the information processing occurring under oscillatory activity in both the healthy and pathological brain states.

Keywords: neural networks,functional cell assemblies,sharp wave,epilepsy,3d two-photon imaging,bulk loading,neurophysiology,intact hippocampus,interneurons,hs cells,lfp,patch clamp,hub cells.
Sulfation pathways in Health and Disease: SUPA-HD (SUPA-HD)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-2013-IEF, 2013)
Start date: 2014-03-01
End date: 2016-02-29
Duration (months): 24.0
Total project cost (EUR): 309235.2
EU funding (EUR): 309235.2
Participants: 1
Project status: CLOSED

Sulfated biomolecules are omnipresent in biology. Highly diverse biomolecules are sulfated by an armada of sulfotransferases that depend on provision of active sulfate in the form of 3’-phospho-adenosine-5’-phosphosulfate (PAPS) for action. In humans, PAPS is exclusively provided by the two bifunctional PAPS synthases PAPSS1 and PAPSS2. A growing number of studies report patients with various mutations in the PAPSS2 gene with clinical phenotypes ranging from bone and cartilage mal-formations to severely disturbed androgen metabolism. PAPSS2 has been characterised as an unstable protein. The nucleotide APS (adenosine-5’-phosphosulfate) is a specific stabiliser of PAPSS2 in vitro. However, the cellular concentration of APS, and the related nucleotides PAPS and PAP are unknown. Within the cell, scaffold proteins or chaperones may be involved in stabilising the PAPSS2 protein. Furthermore, nuclear or cytoplasmic PAPSS variants were analysed within the context of DHEA sulfation. We observed that cytosolic PAPSS2 supported DHEA sulfation by cytoplasmic sulfotransferase SULT2A1 to a larger extent than cytosolic PAPSS1. PAPSS2 may hence be involved in various, yet unknown protein interactions. The present proposal combines the biochemical expertise of the Applicant with the profound endocrinology and translational knowledge of the Host as well as the excellent know-how for targeted metabolite quantification that exists in Birmingham. With these pillars we are in the unique position to correlate the cellular phenotypes with the different disease-causing PAPSS2 mutations, to find novel protein interaction partners of PAPS synthases by proteomics and to develop and apply innovative analytical methodology to quantify APS, PAPS and PAP within mammalian cells.

Keywords: 3'-phospho-adenosine-5'-phosphosulfate (paps) synthase,adenosine-5'-phosphosulfate (aps),protein stability,protein interaction,steroid sulfation,lc-ms/ms targeted metabolite quantification
Do individuals with intellectual disabilities have an abnormal physiological response to exercise? (ID PHYSIOLOGY)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Outgoing Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Netherlands
Call:  (FP7-PEOPLE-2013-IOF, 2013)
Start date: 2015-07-01
End date: 2017-06-30
Duration (months): 24.0
Total project cost (EUR): 173640.3
EU funding (EUR): 173640.3
Participants: 1
Project status: CLOSED

Individuals with intellectual disabilities (ID) are important consumers of health care, partly due to high prevalence rates of inactivity-related health conditions. So far, adapted physical activity interventions have focused mostly on organizational and behavioural aspects, with disappointing results. In these studies, physiological aspects such as cardiorespiratory capacity or energy cost of activities, were not taken into account or were assumed to be similar to the general population. However, abnormalities in the autonomic response to exercise and higher energy cost of activities have been demonstrated in small and selected samples of the ID population, mostly in people with Down syndrome. The aim of this research proposal is therefore to discover physiological barriers, that influence physical activity and exercise in people with ID. Risks of not knowing about these barriers are fatigue, injury and lack of motivation of people with ID, in a vicious circle leading to loss of functioning and health conditions. During the outgoing phase, I will unravel (abnormalities in) the autonomic cardiorespiratory response of people with ID, using different sympatho-excitatory tasks. During the return phase, I will investigate absolute and relative energy cost (related to cardiorespiratory capacity) of walking in people with ID, and analyze the association with their physical activity levels. By revealing an essential missing link, this project is expected to make the difference in what has not been achieved so far: a successful long-term approach to prevent health risks and preserve daily functioning skills, by keeping this population as active and fit as possible. The acquired knowledge will greatly benefit the return host. With this study, I will expand my knowledge and skills, build strong international collaborations, and develop towards the position of a leading, independent researcher with my own research line on physical activity and fitness in people with ID.

Keywords: exercise physiology,intellectual disability,physical activity,public health
Spiritual Brains and Embodied Minds: Neural Bases of Self-Transcendence and Empathy (SPIRIT)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-2013-IEF, 2013)
Start date: 2014-09-01
End date: 2016-08-31
Duration (months): 24.0
Total project cost (EUR): 309235.2
EU funding (EUR): 309235.2
Participants: 1
Project status: CLOSED

The representation of our own and others’ mental events is strongly linked to mapping internal bodily states (embodiment). At the same time, the ability to transcend actual body perceptions and actions (self-transcendence) and to project self-images into scenarios that are not entirely transparent to sense modalities (spirituality) is inherently linked to human beings. Recent neuroimaging studies have addressed the issue of the neural correlates of spiritual experiences and empathy. Information on how the activation of spiritual self-representations impacts the embodied understanding of others’ mental states, however, is inconclusive and causative evidence on this link is scarce. SPIRIT aims to study the cognitive processes and neural mechanisms underpinning the influence of self-transcendence and spirituality on the embodied instantiations of social perception and empathy. In particular, SPIRIT will study the: a) Neural correlates of implicit and explicit spiritual representations of the self; b) Effects of the activation of self-transcendence representations following spiritual word priming or meditation practice on the cognitive processes and the neural correlates of empathy for pain. c) Short-term plastic changes of spiritual self-representations and empathy induced by neurophysiologic regulation of neural activity. Integrating the brain stimulation expertise of the fellow with learning state-of-the-art neuroimaging methods, SPIRIT fosters a multimodal approach to explore how the complex neurofunctional organization of the human brain allows the development of spiritual self-representations and the reaching of more abstract (dis-embodied) forms of social perception. This approach will be disseminated in academic seminars and in international public conferences for lay people. Merging together the study of spirituality, self-transcendence and embodied social cognition will ultimately allow a better understanding of how the brain represents the social self.

Keywords: self-transcendence,spirituality,body schema,empathy,embodiment,meditation,social perception,parietal cortex,transcranial magnetic stimulation,functional magnetic resonance imaging.
Role of nuclear architecture in cancer development (ACTINNUCLSHAPECANCER)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-2013-IEF, 2013)
Start date: 2014-04-01
End date: 2016-03-31
Duration (months): 24.0
Total project cost (EUR): 231283.2
EU funding (EUR): 231283.2
Participants: 2
Project status: CLOSED

Nuclear shape is one of the gold standards for detection and characterization of cancers. Nonetheless the control of nuclear morphology and its relationship to malignant behaviors are still poorly understood. We propose to study the mechanisms that lead to nuclear dysmorphia and their consequence on nuclear functions such as genome integrity and migration. The first part of the research will start from a list of actin regulators that, in preliminary experiments, showed role in controlling nuclear shape and/or DNA repair. An integrated combination of cutting edge biophysical and imaging techniques will be exploited to analyze in detail the biophysical features of nuclei and to address the potential role of the different pools of actin on nuclear shape and deformability. A relevant part of the project will be dedicated to characterize the molecular mechanisms downstream of the candidate genes and to test their role in the context of 3D migration and genome integrity. Nuclear size and stiffness represent a significant obstacle to cell migration. However, cancer cells successfully shape their nuclei to efficiently migrate through gaps with otherwise limiting dimensions. In final part of our proposal we plan to perform a RNA interference screening to isolate genes that allows migration through limiting-size pores. The candidate hits will then be studied for their role in nuclear architecture and functions. Our proposal supports the idea that the nuclear structure might be a bridge between different hallmarks of cancer and might uncover a new layer of the control of these aggressive traits in cancer.

Keywords: actin,cancer biology,nuclear shape,nuclear biophysics,cell migration,metastasis,dna damage,genomic instability,live-cell imaging
Adaptive Optimal Estimation and Control for Automotive Engine Systems with Approximate Dynamic Programming (AECE)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-2013-IEF, 2013)
Start date: 2015-01-05
End date: 2017-01-04
Duration (months): 24.0
Total project cost (EUR): 231283.2
EU funding (EUR): 231283.2
Participants: 1
Project status: CLOSED

According to the latest global energy policy, more than 630 million vehicles are expected to be added to the Indian, Chinese, US, and EU fleets between 2000 and 2030. This growth increases requirements for fuel economy and necessitates the development of automotive engine management systems using advanced estimation and control approaches. This project is dedicated to study a novel online optimal adaptive estimation and control framework and to address their applications to engine estimation and control (e.g. torque estimation and air-fuel-ratio (AFR) control) in particular for turbocharged engines. A recently developed bio-inspired approach, approximate dynamic programming (ADP), will be exploited so that the estimation or control for an optimal performance index can be online solved without precise models. A laboratory engine test-rig will be used for experiments. Specific objectives to support the overall project are: 1) Revisit and improve engine models to account for the delays between the intake fuel injection event and torque output induction event; 2) Develop an adaptive parameter estimation approach to determine engine model parameters within finite time and with guaranteed transient performance; 3) Investigate an ADP-based adaptive observer for engine state estimation (e.g. torques, intake pressure); 4) Study ADP-based optimal adaptive control for complex nonlinear systems and exploit its application in terms of engine control to minimize the effect of cyclic dispersion and to allow for improved AFR performance. The project will be conducted in close collaboration with other academic institutions (University of Bath) and industry (Jaguar Land Rover). The research outcomes could lead to significant advances in both academic research and engineering applications. Thus, it is paving a way for further theoretical developments in optimal theory and also for bridging the gap between optimal adaptive control techniques and their application to automotive systems.

Keywords: automotive engines,optimal control,adaptive control,approximate dynamic programming (adp),engine torque estimation,air-fuel ratio control
A Reloadable Molecular Peptide Synthesizer (RELOADPEPSYN)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-2013-IEF, 2013)
Start date: 2014-04-01
End date: 2016-03-31
Duration (months): 24.0
Total project cost (EUR): 231283.2
EU funding (EUR): 231283.2
Participants: 1
Project status: CLOSED

The sequence-specific synthesis of information-rich oligomers and polymers is achieved in nature through the operation of complex molecular machines that transcribe information from the genetic code. The most extraordinary of these ‘molecular factories’ is the ribosome, a molecular machine found in all living cells that assembles amino acids from transfer RNA (tRNA) building blocks into a peptide chain with an order defined by the sequence of the messenger RNA (mRNA) strand that it moves along. The Leigh group recently reported the design, synthesis and operation of a rotaxane-based small-molecule machine in which a functionalized macrocycle operates on a thread containing peptide building blocks in a pre-determined order to achieve sequence-specific peptide synthesis. Limitations of the first generation system include that it erases the sequence information on the strand as it is translated into the product. In this project I aim to protect the information during peptide synthesis in order to mimic multiple translation, the process through which protein is synthesized on the mRNA template by the ribosome. This will be achieved through a reloadable track strategy in which longer peptide chains than has previously been possible will be synthesized and the machine itself will be usable multiple times. Importantly, the peptide loading units are easy to attach and detach from the thread using hydrazone and Pd-metal complex ligand exchange reactions. Achieving a synthetic molecular machine that can do this specific task, i.e. synthesizing a peptide multiple times, will be a major advance in this field.

Keywords: organic chemistry,supramolecular chemistry,rotaxane,synthetic molecular machines