ERC FUNDED PROJECTS

Asymmetric cell division is a key mechanism for the generation of cell diversity in eukaryotes. During this process, a polarized mother cell divides into non-equivalent daughters. These may differentially inherit fate determinants, irreparable damages or age determinants. Our aim is to decipher the mechanisms governing the individualization of daughters from each other. In the past ten years, our studies identified several lateral diffusion barriers located in the plasma membrane and the endoplasmic reticulum of budding yeast. These barriers all restrict molecular exchanges between the mother cell and its bud, and thereby compartmentalize the cell already long before its division. They play key roles in the asymmetric segregation of various factors. On one side, they help maintain polarized factors into the bud. Thereby, they reinforce cell polarity and sequester daughter-specific fate determinants into the bud. On the other side they prevent aging factors of the mother from entering the bud. Hence, they play key roles in the rejuvenation of the bud, in the aging of the mother, and in the differentiation of mother and daughter from each other. Recently, we accumulated evidence that some of these barriers are subject to regulation, such as to help modulate the longevity of the mother cell in response to environmental signals. Our data also suggest that barriers help the mother cell keep traces of its life history, thereby contributing to its individuation and adaption to the environment. In this project, we will address the following questions: 1 How are these barriers assembled, functioning, and regulated? 2 What type of differentiation processes are they involved in? 3 Are they conserved in other eukaryotes, and what are their functions outside of budding yeast? These studies will shed light into the principles underlying and linking aging, rejuvenation and differentiation.

2 200 000 €

Start date: 2010-05-01, End date: 2015-04-30

CoralWarm will generate for the first time projections of temperate and subtropical coral survival by integrating sublethal temperature increase effects on metabolic and skeletal processes in Mediterranean and Red Sea key species. CoralWarm unique approach is from the nano- to the macro-scale, correlating molecular events to environmental processes. This will show new pathways to future investigations on cellular mechanisms linking environmental factors to final phenotype, potentially improving prediction powers and paleoclimatological interpretation. Biological and chemical expertise will merge, producing new interdisciplinary approaches for ecophysiology and biomineralization. Field transplantations will be combined with controlled experiments under IPCC scenarios. Corals will be grown in aquaria, exposing the Mediterranean species native to cooler waters to higher temperatures, and the Red Sea ones to gradually increasing above ambient warming seawater. Virtually all state-of-the-art methods will be used, by uniquely combining the investigators expertise. Expected results include responses of algal symbionts photosynthesis, host, symbiont and holobiont respiration, biomineralization rates and patterns, including colony architecture, and reproduction to temperature and pH gradients and combinations. Integration of molecular aspects of potential replacement of symbiont clades, changes in skeletal crystallography, with biochemical and physiological aspects of temperature response, will lead to a novel mechanistic model predicting changes in coral ecology and survival prospect. High-temperature tolerant clades and species will be revealed, allowing future bioremediation actions and establishment of coral refuges, saving corals and coral reefs for future generations.

3 332 032 €

Start date: 2010-06-01, End date: 2016-05-31

Chronic pain syndromes are to a large extent due to maladaptive plastic changes in the CNS. A CNS area particularly relevant for such changes is the spinal dorsal horn, where inputs from nociceptive and non-nociceptive fibers undergo their first synaptic integration. This area harbors a sophisticated network of interneurons, which function as a gate-control unit for incoming sensory signals. Several different types of interneurons can be distinguished based e.g. on their neurotransmitter and neuropeptide content. Despite more than 40 years of research, our knowledge about the integration of these neurons in dorsal horn circuits and their contribution to sensory processing is still very limited. This proposal aims at a comprehensive characterization of the dorsal horn neuronal network under normal conditions and in chronic pain states with a focus on inhibitory interneurons. A genome-wide analysis of the gene expression profile shall be made from defined dorsal horn interneurons genetically tagged with fluorescent markers and isolated by fluorescence activated cell sorting. A functional characterization of the connectivity of these neurons in spinal cord slices and of their role in in vivo sensory processing shall be achieved with optogenetic tools (channelrhodopsin-2), which permit activation of these neurons with light. Finally, behavioral analyses shall be made in mice after diphteria toxin-mediated ablation of defined interneuron types. All three approaches shall be applied to naïve mice and to mice with inflammatory or neuropathic pain. The results from these studies will improve our understanding of the malfunctioning of sensory processing in chronic pain states and will provide the basis for novel approaches to the prevention or reversal of chronic pain states.

2 467 000 €

Start date: 2010-05-01, End date: 2016-04-30

Plants and their pathogens are in a constant process of co-evolution. Consequently, many of the known defense genes of plants against fungal pathogens are rapidly loosing effectiveness under agricultural conditions. However, there are examples for durable resistance. It is one of the main research questions in plant biology to determine the genetic basis of such naturally occurring resistance and to understand the underlying biochemical and molecular cause for durability. This durability is characterized by the apparent inability of the pathogen to adapt to the resistance mechanism. The molecular understanding of durable resistance will contribute to future attempts to develop such resistance by design. We want to use two approaches towards understanding and developing durable resistance: the first one is based on the naturally occurring durable resistance gene Lr34 against rust and mildew diseases in wheat. This gene was recently isolated in our group and it encodes a putative ABC type of transporter protein, providing a possible link between non-host and durable resistance. Its function in resistance will be studied by genetic and biochemical approaches in the crop plant wheat, as there is no Lr34-type of resistance characterized in any other plant. However, there is a close Lr34-homolog in rice and its function will be investigated in this diploid system. The second approach will be based on natural diversity found in a specific resistance gene, conferring strong, but not durable resistance. This diversity will be used for a designed improvement of durability by developing new proteins or protein combinations to which the pathogen can not adapt. We will use the 15 naturally occurring alleles of the Pm3 powdery mildew resistance genes to identify the structural basis of specific interactions. Based on this characterization, we will develop intragenic or gene combination pyramiding strategies to obtain more broad-spectrum and more durable resistance.

2 100 000 €

Start date: 2010-04-01, End date: 2015-03-31

Background: Poor angiogenesis and collateral vessel formation lead to coronary heart disease, claudication, infarctions and amputations while malignant glioma is one of the most aggressive proangiogenic tumors leading to death in a few months. For these diseases either stimulation or blocking, respectively, of angiogenesis may provide novel treatment options. Advancing State-of-the-Art: Our hypothesis is that in ischemia it will be possible to support natural growth of blood vessels with Therapeutic angiogenesis and lymphangiogenesis by using local gene transfer of the new members of vascular endothelial growth factor (VEGF) family and their receptors. New co-receptors, designer mutants and PCR suffling products of VEGFs will be used. New vector technology will be used to achieve long-lasting effects of VEGFs. We aim to develop novel site-specifically integrating, targeted, regulated vectors to precisely express the new VEGFs, their soluble decoy receptors and single-chain therapeutic antibodies (scFv) for pro- and anti-angiogenic purposes. As novel approaches, we have developed metabolically biotinylated lenti- and adenoviruses suitable for targeting and Epigenetherapy where siRNA/miRNAs and short nuclear RNAs regulate endogenous gene expression at the VEGF promoter level via modification of histone code. scFv library for endothelial cells and lentivirus-siRNA library directed to all human and mouse kinases will be screened to identify new mediators of angiogenesis in order to develop next generation pro- and antiangiogenic therapies. Based on our strong track record in Clinical applications, the best new pro- and antiangiogenic approaches will be taken to phase I clinical studies in myocardial ischemia and malignant glioma. Significance: This work should lead to significant advances and new therapies for severe ischemia and malignant glioma. Epigenetherapy and new site-specifically integrating, regulated vectors should be widely applicable in medicine.

2 200 000 €

Start date: 2010-06-01, End date: 2015-05-31

One of the key challenges in scientific research is to link together our understanding of different levels of biological organisation. This challenge is fundamental to the scientific endeavour: from understand how genes interact to drive the cell, to how cells interact to form organisms, up to how organisms interact to form groups and societies. My own and the research of others has addressed this question in the context of the collective behaviour of animals. Mathematical models of complex systems have been used to successfully predict experimental outcome. Most previous studies are however limited in one important aspect: individuals are treated as identical units. The aim of the proposed research proposed is to investigate features which produce differences within the units. The model systems of our study will be sticklebacks, homing pigeons and house sparrows. Individuals can differ from each other on a range of time scales, from information acquired within the last few minutes, through socially learnt information, to genetically inherited differences. Through a series of experiments on each of the study species, the development of mathematical models which incorporate between individual differences, and novel forms of data analysis, we will begin to understand the role played by individual differences within groups. We will look at the rules of motion for fish and birds; the role of personality in decision-making and how short term information differences improve decision-making accuracy. Achieving the project objectives will greatly enhance our understanding of the relationship between individual animals and the groups they live in, as well as impacting on our understanding of individual differences in other areas of biology.

977 768 €

Start date: 2010-02-01, End date: 2015-01-31

The aim of this project is to try to understand the complex molecular mechanisms involved in DNA editing, repair and recombination during immunoglobulin class switch recombination (CSR) and somatic hypermutation (SHM). We have developed a series of PCR-based assays to study in vivo generated CSR junctions and the pattern of mutations introduced in the immunoglobulin variable region genes in human B cells, allowing us to characterize CSR and SHM in patients with immunodeficiency due to defect(s) in DNA repair/recombination. Novel in vitro CSR assays, based on GFP expression, allowing quantitative measurement of substrate recombination, are also being developed. In addition, we have initiated an evolutionary analysis of the function and structure of activation-induced deaminase, an essential molecule involved both in CSR and SHM, aiming to identify CSR specific-cofactor(s). Combining these approaches, we will be able to define the DNA repair pathways involved in CSR and SHM. The suggested project requires access to patients with various defects in the DNA repair pathways. Many of these diseases are exceedingly rare. However, through worldwide collaboration, we have obtained samples from a majority of the diagnosed patients. We are also refining the existing screening methods and developing novel methods, that will allow identification of additional patients both with recognized and new diseases caused by mutations in DNA repair pathways. Finally, we hope to be able to address the question whether illegitimate CSR events are associated with predisposition to lymphomagenesis in patients with immunodeficiency/DNA repair defect(s), by analyzing the CSR induced chromosomal breaks and translocations in these patients. A large-scale sequencing project is also planned to characterize the CSRnome in B-cell lymphoma samples.

1 888 166 €

Start date: 2009-12-01, End date: 2014-11-30

Over the last decade epigenetic gene regulation has become a major focus of scientific research as it was shown to play an important role in normal plant and animal development, but also in the ontogeny of human disease. A role of epigenetic processes in evolution, however, has found little general support to date. The goal of this project is to understand the complex interplay of epigenetic mechanisms in plant development and evolution. Many of the approaches we use rely on the recent advances in sequencing technologies, which allow the analysis of molecular characters at an unprecedented level and speed. To achieve our goal, we will focus on two epigenetic paradigms. In Program A, we will focus on dissecting the mechanisms of genomic imprinting at the MEDEA (MEA) locus in Arabidopsis, which we will investigate using genetic, molecular, and innovative biochemical approaches to gain a comprehensive picture of the complex interplay of various epigenetic pathways. In program B, we will analyze the role of epigenetic change in adaptation and evolution using (i) an experimental selection approach in Arabidopsis, where genome-wide analyses of epigenetic modifications have become possible, and (ii) a stable, heritable, epigenetic change occurring in Mimulus populations. In this system, an epigenetic switch of the pollinator syndrome leads to reproductive isolation and, therefore, has an effect on population structure and thus the evolutionary trajectory. These experimental systems each offer unique opportunities to shed light onto the underlying mechanisms controlling epigenetic states. In combination with the new methodologies used, these analyses promise to provide step change in our understanding of epigenetic processes at the level of genes, organisms, and populations.

2 496 641 €

Start date: 2010-04-01, End date: 2015-12-31

MicroRNAs (miRNAs) are a novel class of genes, accounting for >1% of genes in a typical animal genome. They constitute an important layer of gene regulation that affects diverse processes such as cell differentiation, apoptosis, and metabolism. Despite such critical roles, deciphering the mechanism of action of miRNAs has been difficult, leading to multiple, partially contradictory, models of miRNA activity. Moreover, adding an additional layer of complexity, it is now emerging that miRNA activity is regulated by various mechanisms that we are only beginning to identify. Our objective is to understand how miRNAs are regulated under physiological conditions, in the roundworm Caenorhabditis elegans. We will focus on pathways of miRNA turnover, an issue of fundamental importance that has received little attention because miRNAs are widely held to be highly stable molecules. However, miRNA over-accumulation causes aberrant development and disease, prompting us to test rigorously whether degradation can antagonize miRNA activity and either identify the machinery involved, or confirm the dominance of other regulatory modalities, whose components we will identify. C. elegans is the organism in which miRNAs and many components of the miRNA machinery were discovered. However, previous studies emphasized genetics and cell biology approaches, limiting the degree of mechanistic insight that could be obtained. In addition to exploiting the traditional strengths of C. elegans, we will therefore develop and apply biochemical and genomic techniques to obtain a comprehensive understanding of miRNA regulation, enabling us to demonstrate both molecular mechanisms and physiological relevance. Given the importance of miRNAs in development and disease, identifying the regulators of these tiny gene regulators will be both of scientific interest and biomedical relevance.

1 782 200 €

Start date: 2010-05-01, End date: 2015-04-30

How sensory processing is occurring into the brain and how to relate behavior to neuronal activities are key questions in modern neuroscience. Understanding the neural codes underlying brain function will be of great importance for future implementation of brain-machine interfaces. This research project proposes to study the cellular and network mechanisms controlling sensory perception. In particular, we would like to precise how sensory stimuli are coded by brain networks and how these representations may be influenced by experience or modulatory brain centers. In order to address these general questions, we propose to study olfaction as model sensory system. The olfactory system is central to the behavior of rodents (animal models that we study), is highly plastic and largely modulated by the neuromodulatory brain centers. We propose to use a combination of genetic, electrophysiological, imaging and behavioral methods to study how odor information is processed in the central nervous system as it moves from the periphery to higher areas of the brain. We showed in the past that sensory information can be contained in dynamic neural ensemble. We propose to show that ensemble dynamics may be the basis of odor coding in the olfactory bulb and to describe the mechanisms underlying cortical coding that would allow us to relate neuronal activity to behavior. In addition, we hope to show the existence of a novel form of plasticity in the olfactory bulb namely ensemble plasticity. We believe that the general questions addressed in the study of these sensory systems go beyond understanding olfactory sensory perception and could potentially be generalized to the function of many brain regions.

1 399 998 €

Start date: 2009-12-01, End date: 2014-11-30

To understand the molecular basis of any biological process, it is critical that one is not only able to visualize and monitor molecular events that underlie this process, but also to possess the tools to manipulate these events in a spatial and temporal fashion both in and out of the cell. The overall objective of this proposal is to apply chemical biology approaches to allow real time monitoring of protein aggregation and to dissect the role of specific disease-associated post-translational modifications, phosphorylation, nitration, and truncation on the structure, aggregation, and biochemical properties of monomeric a-syn in health and disease. To achieve these goals, we plan to use a combination of organic chemistry, molecular biology, proteomics, protein engineering, and semisynthetic strategies to facilitate site-specific introduction of post-translational modifications that can be masked and activated in a controllable manner, both inside and outside living cells. Modified synthetic ±-syn will be introduced into primary neurons and cellular models of synucleinopathies and the consequences of masking or activating specific modifications will be assessed using biochemical, immunofluorescence, and live imaging techniques (Specific Aim 1). The absence of specific molecular probes that allow in vivo monitoring and quantitative measurement of toxic misfolded and aggregation intermediates represents a major impediment to understanding the relationship among protein misfolding, post-translational modification, protein aggregation, neurodegeneration, and cell death in PD and other neurodegenerative disorders. To address this challenge, we plan to develop and characterize novel antibodies that target different species along the amyloid formation pathway of ±-syn (Specific Aim 2).

1 495 400 €

Start date: 2009-12-01, End date: 2014-11-30

Aims and significance: The aims of this program are (1) To obtain new understanding of how environmental and life style factors interact with genes to induce immune reactions able to cause the different forms of arthritis that are defined as RA; (2) To use this understanding to develop prevention and targeted therapy for different forms of RA, and to enable efficient and eventually curative therapy. Background: We build on new understanding or RA etiology that has followed from studies on interactions between genes, environment and immunity in different subsets of RA. This has been provided for new detailed studies on specific and eventually disease-inducing autoimmunity in RA. Research program: We will use our infrastructure (longitudinal large cohorts, biobanks genetic information and our molecular immunology laboratory) to investigate (1) how genes and environment interact in causing different forms of RA; (2) how specific immune reactions against post-translationally modified (mainly citrullinated) autoantigens are triggered by environmental agents in specific genetic contexts in different individuals; (3) How these immune reactions target different organs (joints, lungs etc) and eventually cause arthritis in model systems; (4) how the combination of genes, environment and immunity may determine disease course and response to various therapies. Novelty and opportunities to take knowledge of autoimmune disease and RA to a new level: The recent advances in understanding interactions between genes, environment and immunity in RA, provides a striking new opportunity to understand basic features of autoimmunity and autoimmune disease, as well as potentials to prevent and treat RA very early. I believe that the presented program is well positioned to use this opportunity and contribute to a new paradigm for understanding and preventing RA.

2 000 000 €

Start date: 2010-04-01, End date: 2016-03-31

Each year 1.1 million new cases of breast cancer will occur among women worldwide and 400,000 women will die from this disease. Although progress has been made in understanding breast tumor biology, most of the relevant molecules and pathways remain undefined. Their delineation is critical to a rational approach to breast cancer therapy. This proposal focuses on the role of the under-explored family of protein-tyrosine phosphatases (PTPs) in the normal and neoplastic breast. Virtually all cell signaling pathways are modulated by reversible protein tyrosine phosphorylation, which is regulated by two classes of enzymes: protein-tyrosine kinases (PTKs) and PTPs. Not surprisingly, tyrosine phosphorylation has an important role in breast development and cancer. Whereas the role of specific PTKs, like the HER2 receptor, in breast cancer is well studied, almost nothing is known about the function of specific PTPs in this disease. Our preliminary data suggest that PTP1B has an important role in breast differentiation and that both PTP1B and SHP2 play positive roles in breast cancer. The two predominant goals of this proposal are: First, to delineate the role of PTP1B and other PTPs in normal breast development and differentiation; second, to address the roles of PTP1B and other PTPs in the maintenance of breast cancer and metastasis and to assess their merits as drug targets. These studies not only use state-of-the-art ex vivo and in vivo models for studying breast pathophysiology, but also cross the boundaries between the developmental and cancer research fields and between basic science and clinical applications. Our research should ultimately lead to the rational design of targeted therapies that will improve the clinical management of patients with breast cancer.

1 571 365 €

Start date: 2010-02-01, End date: 2015-01-31

We aim to study transcriptomes with single-cell resolution, a long-standing goal in biology, to answer fundamental questions about gene regulation. The main objective concerns gene regulation during in vivo differentiation and in pluripotent cells by studying single-cells from murine preimplantation embryos, a model system with natural single-cell resolution, important biology and medical potential. This would also allow us to explore general regulatory principles of gene expression programs of individual cells. This research program will be accomplished by novel deep sequencing technology of mRNAs (mRNA-Seq) to obtain quantitative, unbiased and genome-wide gene and isoform expression measurements. We are therefore developing new experimental and computational methods for genome-wide analyses of transcriptomes at single-cell resolution. The biological significances of the proposed research are unique insights into early embryonic development. Deep sequencing of transcriptomes will also reveal post-transcriptional gene regulation important for pluripotent cells and identified pluripotency-specific gene and isoform expressions will be important for future stem cell based therapies. The inherit single-cell nature of the model system together with its important biology makes it a model systems exceptionally well suited for a systems biology approach aiming to characterize gene regulation at single-cell resolution. The novel methodology has tremendous potential to enable complete mRNA characterization of individual cells. The deep sequencing approach with state-of-the-art computational analyses is both more quantitative than previous methods and it will give readouts on alternative isoforms generated by alternative promoters, splicing and polyadenylation.

1 654 384 €

Start date: 2010-02-01, End date: 2015-01-31

The hallmark of social insect colonies is reproductive division of labour which is often associated with dramatic morphological and behavioural differences between queens, workers and males. The aim of this proposal is three-fold. First, we will use our recently developed fiducial identification system to investigate the general principles of social organisation and division of labour. The video tracking of workers labelled with markers derived from the augmented reality library ARTag allows us for the first time to distinguish up to 2000 individuals and precisely locate them every 500ms, hence allowing large-scale experiments addressing the question of how the behaviour of individual workers is influenced by the joint effects of environmental factors and social interactions. The second related aim is to investigate how the level of altruism within colonies and the reliability of communication systems are shaped by colony kin structure. Because it is not possible to conduct artificial evolution with social insects we will use a new experimental system consisting of colonies of small mobile robots with simple vision and communication abilities. This system permits to conduct hundreds of generations of experimental evolution in colonies with variable group composition to identify the factors affecting the evolution of altruism and communication. Finally, we will complement these studies with a genetic perspective using a remarkable genetic social polymorphism that we recently discovered in the fire ant Solenopsis invicta. The advent of new ultra high-throughput sequencing techniques will allow us to document the steps involved in the evolution of this genetic social polymorphism and test the suggestion that the chromosome involved in the social polymorphism has the properties of a sex chromosome. This project will be highly interdisciplinary, involving skills in evolutionary biology, the study of animal behaviour, bioinformatics, engineering and molecular biology

2 497 500 €

Start date: 2010-05-01, End date: 2016-04-30

One of the central mysteries of immunology is self-tolerance. How does the human body select ~10e12 T lymphocytes, that are reactive to foreign pathogens but tolerant to normal cellular constituents of the host? Over the last few years, my laboratory identified 2 fundamental mechanisms used by thymocytes to establish T cell tolerance. We demonstrated that the affinity threshold for negative selection is a constant for all thymocytes expressing MHC I restricted TCRs. This binding affinity threshold (KD H 6 ¼M; estimated T1/2 H 2 sec) is the fundamental biophysical parameter used by TCRs to delete autoimmune T cells. We also established how the TCR generates distinct signals for positive and negative selection. At the selection threshold, a small increase in ligand affinity for the T-cell antigen receptor leads to a marked change in the activation and subcellular localization of Ras and mitogen-activated protein kinase (MAPK) signaling intermediates. The ability to compartmentalize signaling molecules differentially within the cell endows the thymocyte with the ability to convert a small change in analogue input (affinity) into a digital output (positive versus negative selection) and provides the molecular basis for central tolerance. In the present application, we plan to fully understand 1-how the biophysical events during antigen binding to the TCR initiate an intracellular signal; 2-how these signals program an unambiguous cell fate and 3-how the system fails, when an autoimmune T cell is generated and activated. We will use a combination of transgenic and knockout mice, biochemistry and molecular imaging to fully define how the TCR functions as a molecular switch.

1 930 000 €

Start date: 2010-04-01, End date: 2015-03-31

The main objective of this interdisciplinary research project is to elucidate regulatory mechanisms through which the circadian timing system coordinates temporal physiology. This system has a hierarchical architecture, in that a master clock in the brain s suprachiasmatic nucleus synchronizes subsidiary oscillators in nearly all body cells. The establishment of phase coherence is obviously of utmost importance in the coordination of circadian physiology. While recent studies have identified feeding cycles, hormone rhythms, and body temperature oscillations as timing cues for peripheral clocks, the molecular makeup of the involved signalling mechanisms is largely unknown. Using liver and cultured cells as model systems, we will employ two innovative strategies for the elucidation of relevant signalling pathways. (1) STAR-Prom (Synthetic TAndem Repeat-PROmoter display), a technique developed in our laboratory, will hopefully identify most if not all immediate early transcription factors activated in cultured cells by rhythmic blood-borne and temperature-dependent signals. (2) A transgenic mouse model with conditionally active liver clocks will be explored in the genome-wide identification of coding and non-coding transcripts whose rhythmic accumulation is system-driven. The in vivo significance of the components emerging from these approaches will be assessed via RNA interference. Thus, relevant siRNAs will be injected into the tail vein of mice, and their effect on the phase of circadian liver gene expression will be monitored in freely moving mice by using whole body fluorescence imaging. Physiologically important components will serve as entry points for the identification of upstream and downstream constituents in the corresponding signal transduction cascades.

2 360 136 €

Start date: 2010-04-01, End date: 2015-12-31

Parkinson s disease is one of the common causes of disability in the aging population, representing a major health problem for the affected individuals and a socioeconomic burden to the society. In the present proposal, the applicant puts forward an ambitious but feasible program to tackle a number of significant issues that remain unsolved in the field. He combines his strong track record in animal models of Parkinson s disease and novel cell and gene therapy-based therapeutic strategies with powerful bio-imaging techniques in order to make bold steps towards translation of new and better treatments to patients suffering from this illness. He does so in a manner that combines, on one hand, the strength of clearly-defined hypotheses and well-established tools for results towards clinical translation, with high-risk high-reward projects that hold the potential to yield ground-breaking discoveries in implementation of novel imaging techniques, on the other.

1 508 940 €

Start date: 2009-11-01, End date: 2014-10-31