In a rapidly changing world, we need operational tools to predict and manage responses of biodiversity. To date, although it is clear from both theoretical and empirical work that adaptation can influence the persistence of populations on short time scales, biodiversity scenarios are conspicuously lacking an evolutionary component. One major limitation to the implementation of scenarios including adaptation dynamics is that our knowledge of evolutionary potential and constraints is still too imperfect. In this project, we propose to improve our understanding of adaptive mechanisms in wild populations by integrating theoretical and empirical approaches in wild bird populations at different spatial and taxonomic scales. Using state of the art molecular and quantitative genetics tools in combination with demographic analysis, we will use several populations / species of birds studied in the long-term to identify i) forces of selection acting on natural populations, and especially forces driven by climate change, ii) environmental factors affecting dispersal rates, with a special interest for habitat structure and fragmentation, iii) ecological and phylogenetic factors shaping genetic architecture and affecting its stability, and iv) which regions of the genome show signatures of selection and are therefore likely to be partially responsible for adaptation to different environments. Using a comparative approach among populations and species will allow investigating evolutionary processes at different time and space scales and hence link micro and macroevolutionary patterns. These results will be included in predictive niche models that will assess to which extent the inclusion of rapid evolution and stability of evolutionary potential are affecting predictions from biodiversity scenarios. Hence our approach should provide new tools at the interplay of ecology and evolutionary biology to quantify to what extent model projections neglecting the adaptive component might bias estimates of species extinction risks which are key parameters for policymakers. Moreover, we will put great emphasis on communicating the importance of the biodiversity/evolution interface by (i) collaborating with policy-makers working on biodiversity within the Food and Agricultural Organisation of the United Nations and by (ii) strengthening citizen science through the organisation of exhibitions and conferences in a leading natural history museum (Museum d’Histoire Naturelle, Paris). All in all, results from this project will provide an integrative picture of factors affecting responses to global change improving fundamental knowledge at the interface of ecology and evolution but also including a resolutely operational dimension.

This project comprises two innovative aspects : A new label free method to detect biomolecular interactions based on light diffraction that uses the latest developments in nanotechnology; and the application of such method to the development of new microRNA and protein biochipsA new detection methodBiochip technology has been used mainly in laboratories for research purposes. However, this technology is expected to expand in the near future to the diagnostic field. In most cases, fluorescence-labelling of the samples to be analyzed on biochips is the method of choice to measure biomolecular interactions. Fluorescence labelling greatly adds to the costs of biochip processing, hampering the implementation of diagnostic biochips as routine tests in hospitals and health care centers.The present project aims at developing a new detection method of biomolecular interactions without a need for fluorescence labelling. This innovative method relies on a light diffraction procedure from a biomolecular grating structured at the nanoscale by soft lithography.Diffraction based detection relies on the patterning of the probe that will recognize the target molecules into a periodic grating. Such grating diffracts incident light at specific angles determined by the light wavelength and the inverse of the pitch (periodic distance between two identical structures). If a probe-target complex is formed, the diffracted intensity will change.New microRNA and protein biochips for cancer diagnosisDetection of cancer-derived proteins present in bodily fluids or detection of cancer-associated microRNAs constitute direct ways to diagnose a number of cancer types. Simultaneous detection of multiple such proteins or microRNAs by means of biochips (microarrays) results in an enhanced diagnostic power. Our goal is to apply light diffraction technology to the detection of interaction between probes on the biochip (antibodies or oligonucleotides) and cancer-derived products (proteins or microRNAs, respectively).Economic impact :Innopsys is an SME developing biotechnology instrumentation. Its last product is a scanner for biochip. The development on diffractive detection has been defined as a priority program with the objective of having a new biochip platform to be commercialized in three years. A doctoral studend has already started to work on this project in collaboration with the LAAS. The result of this technology transfer from LAAS to Innopsys will be a new highly competitive biochip platform that will a have a huge economic impact for Innopsys by increasing its sales and technology portfolio.Proteomika designs and produces antibody biochips (microarrays) for the detection of cancerderived proteins. Detection of antibody-protein interactions relies on fluorescence labeling, often a costly procedure. By using light diffraction as a detection method Proteomika expects to reduce expenses and consequently, reduce the price of its products, which in turn is expected to result in a wider implementation of its diagnostic systems in the clinic.Actigenics designs and produces microRNA biochips together with the Biochip platform (PBGT), for the detection of molecular biomarkers involved in disease tissues (cancer, immune diseases).MicroRNA detection using current labeling fluorochrome methods has some limitations. Indeed one of the major challenges in microRNA detection is the fact that microRNA only represent 0.1% of total RNA, which requires at least 5ug of total RNA to start with. By using light diffraction we expect to reduce both the costs associated to current labeling methods but also to increase sensitivity and allow for the development of novel microRNA chips able that need lower quantities of microRNA.More precise and cost-effective diagnostic methods will also result in a reduction in patient management costs, and therefore in a direct benefit for health care systems.

The neocortex represents the brain structure that has been subjected to a major expansion in its relative size and complexity during the course of mammalian evolution. The number of cortical neurons and of functional areas is expanded in primates. An exquisite coordination of appropriate growth of competent territories along multiple axes and their spatial patterning is required for early regionalization of the cortical primordium and the formation of areas in the adult. The achievement of such a highly complex architecture relies on a precise orchestration of the proliferation of progenitors, onset of neurogenesis, spatio-temporal generation of distinct cell types and control of their migration. Growing evidence supports the notion that the aetiology of numerous neurological and psychiatric illnesses, ranging from epilepsy to mental retardation, as well as cortical dysplasia, has to be found in alterations of developmental processes. We have shown that Dbx1 progenitors at the borders of the developing pallium give rise to highly migratory cells which will distribute over long distances from their generation site and which will be present only for a transient period during development. Using genetic tracing we observed that a high number of Dbx1-derived “transient” glutamatergic neurons exists in the telencephalon, in addition to the already known Cajal-Retzius (CR) and pioneer neurons. By conditional genetic ablation we have shown that the presence of Dbx1-derived transient neurons is crucial for the development of the cerebral cortex and for the establishment of functional cortical networks. Namely, Dbx1-derived CR subtypes in the marginal zone/layer I and transient neurons of the cortical plate (CP) are involved in tangential (early regionalization and formation of cortical areas) and radial growth of the neocortex, respectively, by “signaling” to cortical progenitors in a cell non-autonomous manner. Our work indicates that a new strategy appears to be set up in long-range patterning of the cerebral cortex, in addition to passive diffusion of morphogens, through migration of “signaling” cells. The role of the pallial-subpallial boundary (PSB), the site of origin of these transient migrating neurons, in neocortical evolution has been the subject of debate for many years but remains to be established. Together our results show that the PSB generates consecutive waves of migrating transient glutamatergic neurons which from their positions within the marginal zone (CR) and the CP participate in coordinating the formation of cortical areas and the fine tuning of neocortical neuronal numbers, respectively. They strongly suggest that the acquisition of new progenitor domain(s) at the PSB and of tangentially migrating transient “signaling” cells in mammals could be one of the evolutionary additions to pattern large structures, such as the cerebral cortex, and to increase vertebrate brain complexity and cognitive function. This proposal aims at molecularly dissecting how “transient” cells exert their “signaling” function in neocortical development and how preventing their death at the completion of corticogenesis will alter cortical networks. We plan to use genome-wide expression profiling and gain-of-function and loss-of- function experiments in mice together with videomicroscopy and analysis at single cell resolution to study how Dbx1-derived transient neurons serve a function of structural organizers during corticogenesis and to test how their molecular manipulation could provide new genetic tools to develop strategies for rescuing cortical abnormalities using migrating "signaling" cells as vectors for long-range transport of therapeutic molecules.