The centrosome is one of the main microtubule-organizing centers in cells, spawning filaments that define the cell’s shape and polarity. Peculiarly, it is almost always positioned either at the center of the cell or at its periphery, rarely in between. Precise centrosome positioning is crucial: when positioned in the center, the centrosome has the fundamental task of integrating information from the whole cell via the microtubule network. Instead, its swift transition to the periphery is a key step of cell differentiation and polarization. Yet, despite its importance, the mechanism regulating this transition is unknown: several factors are probably involved and regulated in the process, including forces due to molecular motors or to the dynamics of the actin and microtubule networks. In particular, the role of the actin network inside which the microtubules are embedded is starting to be understood as a fundamental player, yet the precise physical mechanism is not understood. This project consists in resorting to the in vitro reconstitution of both the actin and the microtubule networks at the same time, to study their interaction in a minimal biomimetic system. Using an artificial centrosome spawning microtubules and embedding it inside an artificial actin cortex in a dynamic state, adding molecular motors to provide activity and confining it inside cell-sized microwells, we aim to understand how a sharp center to periphery transition can occur and what are the physical processes involved. The possibility to add different purified components one at a time will allow exploring what role factors such as motor- and polymerization-based forces or the mechanical coupling to a contractile actin network play, individually and combined, in defining and controlling precise centrosome positioning. The project paves the way for the understanding of centrosome positioning in cells but also represents an big step in the ongoing effort to build a synthetic cell "from scratch".

The technology of femtosecond lasers now makes it possible to reach enormous light intensities with only moderate amounts of energy. These so-called Ultra-High Intensity (UHI) lasers have led to the development of a very active research field, which studies the interaction of light with matter at these extreme intensities. This field is largely motivated by the prospects of generating compact sources of high-energy particles and short-wavelength light, which are being foreseen for applications in particle physics, material science, nuclear fusion technology, medicine. The actual feasibility of the promising applications of UHI lasers will largely depend on the availability of more reliable and controlled laser systems. In this context, the recent results obtained in the framework of the ERC project PLASMOPT have shown that both major obstacles and great prospects towards this goal are related to space-time couplings (STC) – i.e. a spatial dependence of the laser pulse temporal structure. Yet, there is still no device capable of measuring these STC. The goal of the present project is thus to bring up on the market the first STC measurement device, called TERMITES. This will allow identifying the source of the residual STC, and then eliminating them to reach optimal performances, thus reducing the cost needed to reach a given laser peak intensity by hundreds of k€ or more. It will also have indirect societal benefits, by contributing to the maturation of the technology of UHI lasers, and thus favouring their foreseen societal and industrial applications. Two key tasks of this project are 1- building two to three industrial demonstrators of TERMITES and 2- using these demonstrators to perform a test and validation campaign on a representative set of fs lasers. Depending on the findings of this campaign, this device will be commercialized either through a technology transfer through licensing to an existing company, or through a start-up creation.

Breast cancer is the most common cancer in women worldwide, with nearly 1.7 million new cases diagnosed in 2012. Fortunately, the availability of diagnosis tools to detect mammary neoplastic tissues, as well as transcriptomic biomarkers helping for prognosis, and the diversity of treatment options for primary tumors allows a 90% 5-year survival rate. However the metastatic grade of breast cancer is still not curable. Advances from basic research in the last decade outline the epithelial-to-mesenchymal transition (EMT) as a key program of molecular events triggering metastatic dissemination [Nieto MA, Cell, 2016]. Impairing the EMT process appears as a very seductive way to cure breast carcinoma cancer. Based on preliminary results obtained from “SPICY” ERC Frontier Research Starting Grant, in which we successfully develop an assay dedicated to characterize the EMT state of breast carcinoma cells [Thery M, EP 2180042 A1, 2008 ; Burute M, Dev. Cell, 2016], MATADOR is an ERC proof-of-concept project which proposes a genuine innovative strategy to develop marketable cell based assays allowing the discovery of new drugs efficiently curing mammary tumors, and create a CRO-type biotechnology company exploiting the pre-existing and newly created intellectual property: including marketable assays and therapeutics defined in MATADOR.

Mathematics is a fundamental tool by which we understand the universe, yet its cognitive and brain mechanisms are vastly understudied. I propose a systematic study of the human representation of mathematical concepts and their growth with education. The project will test the “language of thought” theory according to which humans share core concepts with other animals (numbers, objects, shapes, spatial maps) but the growth of math relies on a human symbolic composition system that recursively recombines those concepts into arbitrarily more complex expressions. Work package (WP) 1 will generate maps of mathematical concepts in adults varying in education, using high-resolution single-subject 7T fMRI and MEG. The impact of education will be studied by testing concepts ranging from elementary to advanced, and by comparing adults whose education varies from high-school to professional math. Blind and high-functioning autism subjects will also be tested. WP2 will focus on 5 concepts of central importance in math (geometrical shape, pattern, set, number line, and graph). For each, we will map developmental change by acquiring behavioral and fMRI data in adults and children. The model predicts that concept acquisition can be modeled as a construction of increasingly complex mental expressions whose complexity is predicted by minimal description length (MDL). WP3 will map the brain changes during the acquisition of a math concept. Experiments will test the role of feedback, repetition, retrieval practice, sleep, conceptual diversity, and age, in facilitating behavioral and brain measures of conceptual change. Finally, WP4 will examine whether artificial neural networks can capture the above results and investigate how these networks can be enhanced to achieve human-like performance. Overall, the results will shed light on how mathematical education changes the human brain and how conceptual change occurs, thus paving the way to real-life educational applications in schools.