ERC FUNDED PROJECTS

The Aryl hydrocarbon receptor is an evolutionary conserved widely expressed transcription factor that mediates the toxicity of a substantial variety of exogenous toxins, but is also stimulated by endogenous physiological ligands. While it is known that this receptor mediates the toxicity of dioxin, this is unlikely to be its physiological function. We have recently identified selective expression of AhR in the Th17 subset of effector CD4 T cells. Ligation of AhR by a candidate endogenous ligand (FICZ) which is a UV metabolite of tryptophan causes expansion of Th17 cells and the induction of IL-22 production. As a consequence, AhR ligation will exacerbate autoimmune diseases such as experimental autoimmune encephalomyelitis. Little is known so far about the impact of AhR ligands on IL-17/IL-22 mediated immune defense functions. IL-22 is considered a pro-inflammatory Th17 cytokine, which is involved in the etiology of psoriasis, but it has also been shown to be a survival factor for epithelial cells. AhR is polymorphic and defined as high or low affinity receptor for dioxin leading to the classification of high and low responder mouse strains based on defined mutations. In humans similar polymorphisms exist and although on the whole human AhR is thought to be of low affinity in humans, there are identified mutations that confer high responder status. No correlations have been made with Th17 mediated immune responses in mice and humans. This study aims to investigate the role of AhR ligands and polymorphisms in autoimmunity as well as protective immune responses using both mouse models and human samples from normal controls as well as psoriasis patients.

1 242 352 €

Start date: 2009-02-01, End date: 2014-01-31

This four-year interdisciplinary project addresses the question what has been learned through the use of better regulation ? Better regulation is a flagship policy on the Lisbon agenda for growth and jobs. Its aims are to provide new governance architectures for law-making, to increase the competitiveness of the regulatory environment, and to secure wide social legitimacy for multi-level systems of rules. Whilst most of the research has looked at how better regulation is changing, this project will produce findings on what has changed because of better regulation. Theoretically, the project will use (and significantly improve on) theories of policy learning. Empirically, it will cover Denmark, Italy, the Netherlands, Poland, the UK and the EU including multi-level analysis and analysis by sector of regulation. Methodologically, the project will draw on comparative analysis of types of learning, experiments with regulatory policy-makers in six countries and the European Commission, large-n analysis of impact assessments, backward-mapping of legislation (to appraise the role played by better regulation in the formulation or laws in the UK and the EU), meta-analysis of case-studies and co-production of knowledge with better regulation officers. Dissemination will target both stakeholders (i.e., policy officers, civil society organizations, and business federations) and academic conferences in political science, law, and risk analysis, with a major research monograph to be completed in year 4 and a final interdisciplinary conference.

948 448 €

Start date: 2009-09-01, End date: 2013-09-30

"Economists' modern understanding of the functioning of markets is based on the behavioral assumption of individual rationality. Market agents are assumed to hold well-defined preferences and have perfect ability to draw Bayesian inferences in accordance with correct knowledge of the market model and market equilibrium. This research proposal is based on the premise that bounded rationality on the part of consumers is potentially a major source of market friction. My objective is to develop general theoretical tools to investigate this intuition, and to examine whether these tools can be insightfully applied to realistic market settings. So far, the literature on the subject has progressed as a sequence of specific models that capture one aspect of consumer psychology at a time. The challenge is to synthesize and generalize these models into flexible theoretical frameworks for modelling market interaction between profit-maximizing firms and boundedly rational consumers. Hopefully, various aspects of consumer psychology can be embedded into these frameworks, so that analytic results can be stated in terms of general, abstract properties of consumer behavior, rather than in terms of specific psychological effects. In turn, this general analysis is expected to lead to novel applications. Here are some of the general questions that I hope to address. Can we view certain aspects of firms' pricing and marketing strategies as responses to consumers' bounded rationality? To what extent are boundedly rational consumers vulnerable to exploitation by firms? Does competition protect them from exploitation? Does interaction between firms and boundedly rational consumers give rise to inefficiencies, and how are these affected by competition? What is the impact of various regulatory interventions in this context? Do market forces lead firms to ""educate"" or ""debias"" boundedly rational consumers? Does greater consumer rationality imply more competitive industry profits?"

1 098 637 €

Start date: 2008-11-01, End date: 2014-10-31

Breast cancer is a major cause of death in the United States and the Western World. Advanced medical technologies and therapeutic strategies are necessary for the successful detection, diagnosis, and treatment of breast cancer. Here, we propose to use novel technologies (tissue microarrays (TMA) and automated quantivative bioimaging (AQUA)) to identify new therapeutic and prognostic markers for human breast cancer. More specifically, we will study the activation status of a new signaling pathway which we have implicated in breast cancer pathogenesis, using both mouse animal models and cells in culture. For this purpose, we will study the association of CAPER expression with pre-malignant lesions and progression from pre-malignancy to full-blown breast cancer. We expect that this new molecular marker will allow us to improve diagnostic accuracy for individual patients, enhancing both the prognostic predictions as well as the prediction of drug responsiveness for a given patient.

1 500 000 €

Start date: 2010-01-01, End date: 2014-12-31