ERC FUNDED PROJECTS

Wide field panoramic telescopes will become a major force in astronomy over the next decade. They will address a rich set of scientific problems, from ``killer asteroids'' to the cosmic dark energy. Pan-STARRS-1 (PS1), built by the University of Hawaii, is the first of this new generation of telescopes. European astronomers in Germany and the UK, including in the PI's host institute, make up a large fraction of the Science Consortium that, over the next 4 years, will exploit the data. This proposal is focused on the use of PS1 for cosmology. I propose a programme that combines state-of-the-art cosmological simulations and modelling with high-level analyses of the data. The goal is to test core assumptions of the standard cosmogonic model, LCDM, on scales and at epochs where it has not been tested before and where it can, in principle, be ruled out. At the same time, these tests will advance our understanding of the main constituents of our universe (dark matter and dark energy) and of the processes of galaxy formation and evolution. Two types of structure at opposite ends of the cosmological scale, the Milky Way and the large-scale distribution of galaxies at redshifts z<1.5, are ideally suited to this purpose. Studies of the Milky Way will test LCDM predictions for the hierarchical assembly of galaxies and the structure of their dark matter halos. Studies of the galaxy distribution will test LCDM predictions for the growth of structure and the connection between galaxies and dark matter. To link theory and data, I will construct mock catalogues using very large cosmological simulations and sophisticated modelling techniques. These catalogues will have a much broader applicability that just PS1 and I will make them publicly available using e-science techniques.

2 266 850 €

Start date: 2011-05-01, End date: 2017-04-30

The prime objective for every life form is to deliver its genetic material, intact, to the next generation. Each human cell receives tens-of-thousands of DNA lesions per day. These lesions can block genome replication and transcription, and if not repaired or repaired incorrectly, they lead to mutations or wider genome aberrations that threaten cell viability. To counter such threats, life has evolved the DNA-damage response (DDR), to detect DNA damage, signal its presence and mediate its repair. DDR events impact on many cellular processes and, crucially, prevent diverse human diseases that include cancer, neurodegenerative diseases, immune-deficiencies and premature ageing. While much progress has been made in identifying DDR proteins, much remains to be learned about the molecular and cellular functions that they control. Furthermore, the frequent reporting of new DDR proteins in the literature suggests that many others await identification. The main goals for the proposed research are to: identify important new DDR-proteins and DDR-modulators, particularly those responding to DNA double-strand breaks (DSBs); provide mechanistic insights into how these proteins function; and determine how DDR events are affected by chromatin structure, by molecular chaperones and components of the Ubiquitin and Sumo systems. To achieve these ends, we will use molecular biology, biochemical, cell-biology and molecular genetics approaches, including synthetic-lethal and phenotypic-suppression screening methods in human cells and in the nematode worm. This work will not only be of academic importance, but will also indicate how DDR dysfunction can cause human disease and how such diseases might be better diagnosed and treated.

2 482 492 €

Start date: 2011-05-01, End date: 2016-04-30

Biopharmaceutical proteins are typically produced in cultivated mammalian cells, a costly process with limited scalability. Thus products such as monoclonal antibodies are very expensive and often beyond the reach of the world’s poor. The problem is compounded by the fact that important strategies for preventing diseases such as HIV and rabies typically involve large doses of multiple antibodies and other virucidal proteins. Plants have emerged as alternative production platforms for biopharmaceutical proteins because they are less expensive, more scalable and potentially could be transferred to developing countries. Recently, the first products have reached the clinic, but many of them are follow-on products already manufactured in mammalian cells. Here, Prof Julian Ma (St George’s Hospital Medical School, London, UK) and Prof Dr Rainer Fischer (RWTH Aachen University, Germany) aim to develop innovative ways to use plants for the economical, safe and sustainable production of combinations of active pharmaceutical ingredients (APIs) based on recombinant proteins, thereby pushing the boundaries of what can be achieved in plants beyond current capabilities with fermenter-based systems. We will focus on the production of antibodies and lectins against HIV and rabies, with the aim of generating GMP-compliant microbicidal cocktails for evaluation in human trials. Key aspects of the project will include the production of APIs both individually and as combinations in plants, the development of technologies allowing the introduction of transgenes into pre-determined genomic loci, the use of click chemistry to optimize the production and stoichiometry of recombinant protein cocktails, the development of candidate products for both topical and parenteral administration and the development of downstream processing concepts that are transferrable to developing countries, such as minimal processing and processing trains based on pre-assembled disposable modules. We will complete one Phase I clinical trials, each testing a plant-derived product that advances the field in a significant way

3 488 863 €

Start date: 2011-08-01, End date: 2019-01-31

"This project aims to break new ground by reconceptualising the principles-and-parameters approach to comparative syntax, retaining its strengths and attempting to deal with its perceived weaknesses. The central idea is to organise the parameters of Universal Grammar into hierarchies, which define the ways in which properties of individually variant categories may act in concert; this creates macroparametric effects from the combined action of many microparameters. The highest position in a hierarchy defines a macroparameter, a major typological property, lower positions define successively more local properties. Parameter-setting in language acquisition starts at the highest position as this is the simplest choice; acquirers will ""move down the hierarchy"" when confronted with primary linguistic data incompatible with a high setting. Hence the hierarchies simultaneously define learning paths and typological properties. The main task of the project, and most of the time of the research team working on it, will be devoted to attempting to work out on the basis of cross-linguistic data the precise form of major parts of the hierarchies, thus subjecting the theoretical predictions to rigorous empirical testing. This will be done on the basis of secondary data from grammars, from on-line databases (The World Atlas of Languages Structures, WALS, and the Syntactic Structures of the World’s Languages, SSWL), and, where feasible, from native-speaker consultants. The form of the hierarchies makes predictions concerning acquisition, markedness and language change. The project aims to investigate five hierarchies: those determining word-order, null arguments, word structure, discourse-configurationality and case/agreement alignment. These five hierarchies, although not exhaustive, combine to give a typological footprint of many languages, as well as providing the basis for the study of the interaction of micro- and macroparametric interactions."

2 477 106 €

Start date: 2011-06-01, End date: 2017-05-31