ERC FUNDED PROJECTS

Developmental biology seeks not only to learn more about the fundamental processes of growth and pattern per se, but to understand how they synergize to enable the morphogenesis of multicellular organisms. Our goal is to perform real-time analyses of these developmental processes in an intact developing organ. By applying a vital imaging approach, we can circumvent the normal limitations of inferring cellular dynamics from static images or molecular data, and obtain the real dynamic view of growth and patterning. The wing imaginal disc of Drosophila, which starts out as a simple epithelial structure and gives rise to a precisely structured adult limb, will serve as an ideal model system. This system has the combined advantages of relative simplicity and genetic tractability. We will create several innovations that expand the current toolkit and thus facilitate the detailed dissection of growth and patterning. A key early step will be to develop novel reporters to dynamically and faithfully monitor signaling cascades involved in growth and patterning, such as the Dpp and Hippo pathways. We will also implement quantification techniques that are currently being set up in collaboration with an experimental physicist, to deduce, and alter, the mechanical forces that develop in the cells of a growing tissue. The large amount of quantitative data that will be generated allow us derive computational models of the individual pathways and their interaction. The focus of the study will be to answer the following questions: 1) Is the Hippo pathway regulated spatially and temporally, and by what signaling pathways? 2) Do mechanical forces play a pivotal controlling role in organ morphogenesis? 3) What are the global effects on growth, when pathways controlling patterning, cell competition or compensatory proliferation are perturbed? The proposed project will bring the approaches taken to define the mechanisms underlying and controlling growth and patterning to the next level.

2 310 000 €

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

Since the nineteenth century, the reinforced concrete has been generating a vast specialized litterature everywhere in the world. However, none of it has ever tried to make a first assessment of the evolution of one of the most fundamental element in the processing of the reinforced concrete: the formwork; nor have been reconstructed the various ways of processing the surfaces after removal of the formwork in order to get special effects of polished or rustic surface. Therefore, on the subject of manufacturing of the formworks and processing of the surface, there is a true gap in the studies on reinforced concrete that the research The surfaces of cement and reinforced concrete. A history of the formworks and processing of the surface, 1870-2008 intends to fill. Whether historical or operationnal, this gap lacks not only of the context of the evolution from the nineteenth century, but also of a comprehensive outline of the recent production. The purpose of the research is to provide the most comprehensive documentation and the most significant examples of the international architectural production on the subject of formworks and concrete surfaces within the time span considered. Drawing up the outline of the various types of building and processing of the surfaces will be extraordinarily useful for the historiography of architecture, which will hence have a scientific instrument to evaluate the works in terms of connections between form and material in relation to concrete, as well as for the modern formworks in which the technicial and artistical issues of reinforced concrete processing at sight still remain fundamental. The results of the research will be collected in a book with the caracteristics of an essay, consisting of an important written part and an extremely rich iconographic documentation (project drawings, photographs of building sites and tools, etc.); it will be structured as a synthesis between the technical manual and the historical critical essay.

660 000 €

Start date: 2009-03-01, End date: 2015-02-28

This research project aims at the development, analysis and computer implementation of mathematical models of the cardiovascular system. Our goal is to describe and simulate the anatomic structure and the physiological response of the human cardiovascular system in healthy or diseased states. This demands to address many fundamental issues. Blood flow interacts both mechanically and chemically with the vessel walls and tissue, giving rise to complex fluid-structure interaction problems. The mathematical analysis of these problems is complicated and the related numerical analysis difficult. We propose to extend the recently achieved results on blood flow simulations by directing our analysis in several new directions. Our goal is to encompass aspects of metabolic regulation, micro-circulation, the electrical and mechanical activity of the heart, and their interactions. Modelling and optimisation of drugs delivery in clinical diseases will be addressed as well. This requires the understanding of transport, diffusion and reaction processes within the blood and organs of the body. The emphasis of this project will be put on mathematical modelling, numerical analysis, algorithm implementation, computational efficiency, validation and verification. Our purpose is to set up a mathematical simulation platform eventually leading to the improvement of vascular diseases diagnosis, setting up of surgical planning, and cure of inflammatory processes in the circulatory system. This platform might also help physicians to construct and evaluate combined anatomic/physiological models to predict the outcome of alternative treatment plans for individual patients.

1 810 992 €

Start date: 2009-01-01, End date: 2014-06-30

Yeast vacuoles (lysosomes) will serve as an excellent model system: Vacuoles change copy number and size in the cell cycle and upon shifts of media; due to their large diameter (up to 5 µm) these changes can be assayed by fluorescence microscopy and are amenable to genetic screening. Moreover, an in vitro system for vacuole fusion exists and we recently succeeded in reconstituting also cell-free vacuole fission with purified organelles. We will first build an experimental toolkit for vacuole fission to characterize this reaction in detail. Several approaches will be combined: (1) Identification of fission proteins by mutant screening, as well as by candidate approaches, and their localization relative to the fission site; (2) further developing a system reconstituting in vitro fission and efficient methods to quantitate it. (3) creating organelle chips to synchronously study fission on multiple single vacuoles immobilized in a defined orientation. (4) time-resolved confocal microscopy of fission proteins in vivo and in vitro; (5) biochemical characterization of fission protein associations and their changes during fission. These approaches will identify the vacuolar fission apparatus and help to elucidate its functioning. In a second step we will explore how the fission apparatus physically and functionally interacts with the already well-defined vacuolar membrane fusion machinery. We will characterize the impact of cell cycle regulators and signaling pathways on these interactions. These studies will be pioneering in that they will lead us to a comprehensive description of an organelle fission process and of how membrane fission and fusion components are coordinated to control size and copy number of an organelle.

2 310 000 €

Start date: 2009-09-01, End date: 2015-08-31