Host laboratory : Laboratoire d'Etude des Parasites Génétiques (LEPG) Institutions : Centre National de la Recherche Scientifique & University François Rabelais in Tours Yves BIGOT, PhD Laboratoire d'Etude des Parasites Génétiques (LEPG), FRE CNRS 2969 - Université François Rabelais, UFR des Sciences et Techniques, Parc Grandmont, Avenue Monge - 37200 Tours Director : Address : The LEPG is a team created by the university of Tours and the CNRS, whose present basic research project concerns the analysis of the mobility mechanism of the Mariner transposons (MLE). Beyond the basic knowledge of transposition and its possible improvement by engineering for development of gene transfer vectors, the expertise of the laboratory in genomic plasticity and its biochemical approach gives a creative background for studying the impact of genomic instability in malignant tumors.The present proposal to host an ATIP team starting in 2007 is designed in the frame of the development of a new research unit at the University of Tours, for the development of an interdisciplinary and integrated research center on the biology of cancers (GICC : Genomics, Immunotherapy, Chemistry & Cancer). It is aimed to develop links between basic research on : 1. Genome plasticity and gene transfer (Yves Bigot). The principal research orientations of the laboratory are directed towards the establishment of the conceptual bases and of the technical tools necessary to the experimental study of the mechanism of transposition of the Mariner transposons, the activation of its mobility and the definition of the impact of Mariner on the genome. 2. Genomic instability and cancer (Patrick Gaudray). Our general aim is to identify signals that are involved in tumor progression and to understand its relationship with genomic instability in cancerous tumors. Our approach is mostly basic, functional research in various model systems, though with the declared aim to identify target pathways that may be used for therapeutic intervention. 3. Cancer immunotherapy (Hervé Watier). Our aim is to identify immunological, pharmacological and genetic/genomic factors influencing the variability of clinical effects of recombinant monoclonal antibodies, in order to optimise their therapeutic use if they already exist and to help design drugs of the future. 4. Chemistry of cancer targeting biologically active molecules (Marie-Claude Viaud). Our research relates to the development of heterocyclic entities either unknown or difficult of access. The structures of interest comprise one or more heteroatoms such as nitrogen, oxygen, sulfur or phosphorus. These structures can be mono or polycyclic being able to present cycles coupled or connected to each other by sequences of various and varied nature. The scientific projects of each team and those developed jointly will allow the installation of technologies and unique fields of expertise, which will be a characteristic of this new unit. They place the cancerous cell at the center of their concerns with, in the long term, an organization of work of research according to axes' sets of themes which go from the molecule to the patient. A major objective of the future unit is to take a leadership at the European level in its fields of competence: Engineering of non-viral gene transfer functioning ex vivo and subjected to quality control Custom definition of field of DNA recognition domains (ZFD technology) Immuno-pharmacogenetic expertise on the effect of therapeutic antibodies Biology and functional genomics of the tumors Genetics of cancers (family predispositions and somatic genetics) Synthesis new anti-cancer drugs An important characteristic of the GICC project for its development is thus to link interdisciplinary work in basic research and its technological application. Contacts and interactions between the public teams and their biotech/chemistry companies partners constitute an actual basis for the design of a biotechnology platform for health in Tours. The scientific operations supported by the arrival of new projects and/or project leaders will be developed within the framework of the UMR GICC project on aspects complementary to those already existing. These operations will relate to the following fields: Definition of good target antigens for an antibody-mediated anti-cancer immunotherapy Definition of the cellular partners of the transposition Chemical agents able to synergize with antibodies at the level of cytotoxic cells New chemical approaches for imaging the distribution of antibodies in vivo Cells factories & alternatives to production of antibodies in mammalian cells (yeast, plants, etc) The priorities of implementation between these various scientific actions will be established according to candidates.