In the past 5 years, a protein from prokaryotes has revolutionized biology in ways not seen since PCR in the 80s. CRISPR (Clustered regularly interspaced short palindromic repeats) is an adaptive immunity system for bacteria and archaea that fights off viruses by keeping a DNA record of past infections. This CRISPR array is transcribed, matured into short RNAs and loaded into a programmable nuclease (Cas9) that continuously searches for and cleaves DNA matching the loaded RNA guide. Type II CRISPR stands out by its sheer simplicity as it comprises only two parts: a programmable nuclease (Cas9) and a RNA guide (either a chimeric RNA guide or a duplex crRNA:tracrRNA). Gene editing with Cas9 has fast become a plug-and-play routine, and Cas9 is so versatile that it has been retooled to cut-and-paste DNA, activate or repress gene expression, scout around the genome for particular loci, modulate epigenetic activities or fluorescently illuminate chromosomal regions. Beyond gene editing, CRISPR is poised to be a tool of choice for genome-wide screening, gene and cellular therapy, disease modelling or xenograft transplantation. Cas9 has even been proposed to serve as a molecular recorder to continuously log cellular events in a DNA register. Nagging problems remain for safe, efficient and versatile deployment of CRISPR/Cas9 in life sciences, biotechnology and medicine. Specifically controlling Cas9 remains challenging. Once Cas9 and a guide RNA are both present in a cell, the tandem will inevitably cut its target loci, irrespectively of the type, environment or developmental status of the cell. But mistimed or misplaced action of Cas9 could prove detrimental. Distinct cellular types follow distinct developmental programs, and premature intervention by Cas9 could wreak havoc on cellular progeny. Various strategies have been suggested to control Cas9 (namely split enzymes, small molecule induction or photo-activation), but they are rather crude, lack single-cell precision and are not autonomous because they rely on an external operator. Lastly, the delivery of the inducing signal is limiting: optogenetic methods are hindered by the low penetrability of visible light into deep tissues, and the timed delivery of chemical signals to cells with high specificity is challenging. The goal of this project is to conditionally control the cutting of Cas9 in response to internal, tissular or environmental stimuli. To do this, we will bring about the large repertoire of molecular processing tools developed by the community of DNA nanotechnology: not only nanostructured shapes, but also logic circuits, diagnostics systems, autonomous walkers, pattern classifiers... We will adopt a high-throughput approach thanks to the massive parallelism allowed by droplet microfluidics and next generation sequencing. (see confidential part of the application for further details)

Fusion offer the promise of limitless, clean and safe energy. Numerous designs for fusion reactors have been proposed but most have been plagued by instabilities and turbulence which degrade confinement. The main route to improve confinement has been to make reactors larger and larger. This has culminated into an international project of pharaonic proportions, ITER, with a diameter of 30 m. But the economics becomes unfavorable at this gigantic scale, and it is not even sure if ITER will ever be completed. These setbacks have opened a gap for private initiatives. So far, these public and private races toward fusion have been defined by size: How big does a reactor need to be to confine a fusion plasma? Here we ask the opposite question: What is the smallest reactor that can confine a fusion plasma? A natural scale for a plasma is the Debye length ?, which is the length scale over which the charge of a particle is felt before it gets screened by opposite charges. For a fusion, the Debye length is on the order of ?~100 µm, which suggests that the microscale is a natural scale for fusion plasmas. This immediately raises a question: Can we confine a plasma in a micrometric reactor long enough to achieve fusion? This is the fundamental question that we aim to address. If microscale fusion was possible, it would open a new route as microsystems are much cheaper to build and replace, and are more portable than gigantic infrastructures. Dimensional analysis suggests that confinement should be possible with electric potentials achievable in microsystems (~1-100 kV). A major goal of this project will be to validate this dimensional analysis and estimate the confinement time achievable in actual microsystems. We will do so by combining physical simulations tailored for the regime of microscale and by fabricating prototype microsystems to generate, trap and diagnose plasmas.

The fabrication of organic photovoltaic (OPV) devices implies the use of halogeno and/or aromatic solvent to process the active layer. In order to make this technology cleaner, it is necessary to move to eco-friendly solvent and water is the best one. The most common way to develop water-based inks is to formulate organic semiconductors colloidal dispersions. Although this technique has already been successfully applied in the OPV field, devices fabricated using water-based colloidal dispersions still present lower efficiencies than control devices fabricated from halogeno and/or aromatic solvents. The reason behind these limitations can come from different origins: the presence of surfactant, inappropriate morphology of the nanoparticles and/or of on the dense active layer thin film. These different parameters can affect the charge carrier transport properties and exciton dissociation, and, therefore, will impact the photovoltaic properties. However no clear understanding of the impact of organic semiconductors NP morphology on the optoelectronic properties of the final device has been reported yet. WATER-PV aims to overcome these limitations and fabricate state-of-the-art OPV devices using water-based colloidal dispersions. To do so, we will develop a bottom-up approach starting from the precise control of the NP size and morphology. We will then work on the elucidation of the relationship between the morphology and the optoelectronic properties, first at the nanoparticle scale and then on NP assemblies (thin films). The understanding of the charge transport in those structure will guide the development of active layers with the required characteristics (high hole and electron mobilities, balanced charge transport, high exciton dissociation rate). Finally, OPV devices will be fabricated and the photovoltaic properties will be correlated with the electronic characteristics of the active layer. To summarize, the WATER-PV project aims at establishing a clear understanding between the NP and NP assembly characteristics (size, morphology, composition) and the electronic properties of the final OPV devices. This knowledge will guide us to develop highly efficient OPV devices from water-based dispersions.

The Spectral-Swarm-Robotics project is interested in swarm robotics, where a large number of robots with limited computation and communication power are considered. Our goal is to propose new design methods with a particular focus on how agents can diffuse local information within the swarm to reach a collective decision with respect to their environment and task. Our grand objective is to design a swarm robotics system that is encapsulated in a flexible membrane to accomplish tasks that require distributed sensing, decision-making and action. Our building hypotheses are (1) that the role of information diffusion has been overlooked in swarm robotics so far, where the majority of studies use hand-crafted microscopic rules to control the swarm, and (2) that dense swarm of robots where robots may collide with one another have largely been understudied in favour of gas-like swarm density, though physical interactions without computation can yield relevant self-organized collective behaviours. To achieve sensing and information diffusion, we use tools from spectral graph theory and design bio-inspired diffusion models to bridge the gap between the microscopic and macroscopic scales of the robot swarm. To perform coordinated mobility, we build from tools and methods from active matter, a branch of physics that focuses on the motility of multiple energy-dissipating particles, which we have already shown is a relevant paradigm for swarm robotics. Finally, we develop Machine Learning algorithms to optimize both the diffusion and decision-making processes. As a robot swarm involves robots with limited computation capabilities, we propose frugal machine learning methods to be deployed in a distributed fashion within a swarm of robots to perform online learning in open environments.

COVID-19 has reached a pandemic scale in a few months and is devastating the heath systems of many nations. Knowledge of the virus is still parcelar, but asymptomatic but infectious carriers appear to be driving the explosive growth of the disease. In absence of a vaccine, the best way to manage the epidemy is to combine massive testing, contact tracing and isolation. Yet, PCR tests have proved to be in severe shortages in many countries, which has led governments to ration testing to the most severe cases. While PCR is the gold standard and highly sensitive, it has several drawbacks that prevent its use for massive screening: time, cost, complexity, sensitivity to contaminants and inhibitors, need for refrigerated shipping of reagents... In this proposal we propose to adapt bead-based assays (commonly used in immuno testing) to detect the presence of SARS-CoV-2 with a simple equipment (smartphone, optical microscope), within 30 minutes and with reagents that can be shipped by post. More specifically we propose to decorate the viral RNA with micrometric beads, forming clusters with prescribed morphologies. Those clusters are then detected optically and counted with a standard microscope, a LCD digital microscope or a smartphone coupled to a magnifying lens (available for ~10-100 euros on the web). We will strive to simplify the assay as much as possible, so as to make it easy to use to the largest number of healthcare professionals. We will work on sample processing, so that viral RNA can be prepared without the need for RNA extraction kits (which are in severe shortage). This assay will be complementary to PCR, and used for initial but massive screening (for instance in primary care, in mobile detection van, or in general hospital). We hope that it will allow systematic testing of covid, so as to efficiently contain the pathogen,