Intestinal epithelium is a single layer of cells exposed to external aggressive conditions, that is renewed every 4–5 days, that makes it one of the most sensitive part of human body. Its tissue homeostasis is highly sensitive to proliferation and cell migration; events occurring in a specific microenvironment: the intestinal crypt. However, mechanical interaction within this niche may be difficult to observe in vivo and mechanical properties of this model are poorly described. Recent developments in cell imaging and culture, with the creation of artificial tissue respecting natural architecture or organoids, have opened new access for the creation of epithelial tissues models that can easily be virtualized. We propose a combination of ‘computational models’, integrating the Finite Element Method Updated and Deep Learning, and organoids humanly designed ‘biological models’, to characterize colon epithelial structures, offering a promising avenue for fully automated diagnosis analysis.

Within the context of tissue engineering and regenerative medicine, organoids, which are simplified miniature organs, can be considered as building blocks for the fabrication of macroscopic tissues (~mm-cm). The main obstacle to this scaling process is the integration of a perfusable vascular network to avoid cell necrosis due to lack of oxygen and nutrients. Experimentally, we will rely on P#2's expertise in the customized production of organoids using a patented microfluidic technique, and on P#3's expertise in the production of artificial blood vessels (vesseloids). Unlike most of existing techniques that rely on empirical guidelines, MATISSe methodology combines i) an experimental approach guided by self-organization and multicellular positioning and ii) in silico modeling, which will feed on experimental data before guiding the optimization of the different steps towards the production of the final tissue prototype. The mathematical model for tissue growth and self-organization will be developed within the framework of the Thermodynamically Constrained Averaging Theory, a modern theory for multiphase porous systems already validated by P#1 in the field of physical oncology. The vascularized tissue will be modeled as a deformable, reactive and multiphase porous medium with two porous compartments: the first one, called extravascular porosity, is saturated by cell populations and interstitial fluid (mixture of water and nutritive species); the second one, called vascular porosity, represents the volume occupied by the vessels where an oxygenated medium circulates. The extracellular matrix constitutes the solid scaffold of the multiphase continuum. Building on this in vitro-in silico synergy, the overall goal of MATISSe is to provide a computer-assisted methodology for the optimized, multi-scale design of a new generation of vascularized organoid-based artificial tissues. Even though experimental and mathematical modeling grounds on universal biophysical features, tissue specificity will be addressed by aiming for a liver tissue as a proof of concept. The methodology of MATISSe is structured in three steps: 1) The generation of pre-vascularized organoids that will facilitate and accelerate the connections with the larger-scale tissue vasculature. 2) The study of the behavior of a pre-vascularized organoid in proximity to an artificial blood vessel. A process of angiogenesis, i.e. the creation of new micro-vessels growing from the vesseloid, and their connection with the micro-vessels of the organoid (anastomosis) will be studied experimentally by optical imaging in real time and modeled numerically. 3) The assembly of several pre-vascularized organoids around at least two vesseloids playing the role of vein and artery to generate a larger scale vascularized tissue. Indeed, after a phase of merging of the pre-vascularized organoids (coalescence) and of interconnection between the micro- and macro-vascular systems, a perfusable tissue of millimetric size will be obtained. Our consortium led by an applied mathematician expert in porous materials, is completed with i) a physicist expert in tissue engineering and biophotonics, and ii) a biologist expert in angiogenesis and 3D cell models. Our combination aims to propose optimized and robust design rules. Thanks to the support of mathematical modeling, the expected experimental results will constitute a major advance in the field of tissue engineering. Reciprocally, thanks to the support of controlled experiments, the developed mathematical model will constitute an important and versatile tool for digital twinning of biological tissues.

Project COFIPOL is in line with the previous REI project « Polarizing optical fiber at 780 nm », led by the company IXFIBER and Institut d’Optique Graduate School, which allowed the development of a polarizing optical fiber working at 780 nm perfectly consistent with the specified performance. Here, the goal is to use the polarizing fiber developed by IXFIBER to make optical components needed for atom trapping, cooling and manipulation by laser, in the case of Rubidium for this study, in order to be integrated in different types of high accuracy instruments (gravimeters and accelerometers, gyroscopes, atomic clocks). Indeed, polarization quality is a critical parameter to guarantee long term performance of these systems and using polarizing fibers should allow to improve the extinction ratio of the components by several orders of magnitude. Consequently this project should lead to particularly interesting instrumental and commercial repercussions for all the partners of the project. The goal of the project is to make 2 types of beam splitters: - 1x2 splitters, developed by Keopsys, and based on fusion/drawing out, allowing to get a fixed coupled power - adjustable splitters, developed by Innoptics, and based on micro-optics technics and allowing to rule the balance of the output beams power. Components specifications and performance checking will be done by Institut d’Optique Graduate School, in collaboration with µQuanS.

Most types of cell communication in the brain require the transfer of molecules through the extracellular space (ECS). A correct transfer of molecules within the ECS is thus essential to convey both local and long-distance communication. Although ECS is often considered as a static space with foam of molecules, it emerged that components of the extracellular matrix specifically contribute to intercellular communication in the brain. Interestingly, seminal recent discoveries have grounded the hypothesis that neurodegenerative diseases (e.g. Parkinson and Alzheimer) relies on a cell-to-cell prion transfer of misfolded proteins as well as the accumulation of such proteins in the ECS. Clearing of such proteins by changes in the volume of ECS has even been recently suggested as a physiological mechanism, shedding light upon the need for understanding its actual morphology and rheology changes in a pathological context. This would indeed have many implications in the neurodegenerative disease comprehension, early diagnostic and eventually drug development strategy. However, understanding this central compartment has surprisingly been largely ignored, both in the healthy and neurodegenerative brains and it thus represents a knowledge frontier. This ignorance has mainly conceptual and methodological roots, i.e. the static representation of brain tissue and the current lack of dedicated relevant investigation tools. . In this high-risk project, we will develop the tools to intimately explore the ECS, the last “terra incognita” of the brain. Breakthroughs in single molecule imaging dedicated to the study of the brain tissue in different functional states will be required. Based on our unique individual and common expertise, our pioneering main objectives can be enounced as follows: - during the pilot phase of the project, we will establish that luminescent single wall carbon nanotubes (SWCNTs) can act as unique near infrared nano-emitters capable of probing the ECS local environment in living cerebral tissues. To this aim, we will design and combine novel imaging modalities based on SWCNT imaging and 3D diffractive tomography, and use several model systems for fully quantitative biophysical investigations. - during the second phase of the project, we will apply these innovative tools to explore and unravel the early disorganization of the brain ECS in Parkinson’s disease. In particular, we will study the ECS remodeling along the pathology propagation in ground-breaking animal model of Parkinson’s disease we recently validated, deciphering the relationship between ECS spatio-temporal organization, neuronal communication and the neuronal dysfunction, and establishing the proof-of-principle that such innovative tool can be used to diagnose early alteration. The strength of this highly multidisciplinary project relies on an exceptional complementary group formed by 3PIs with unique and world expertise in nano-biophotonics, neurophysiology and neurodegenerative diseases: Cognet (LP2N - Institut d’Optique, CNRS & Univ. Bordeaux), Groc (IINS - CNRS & Univ. Bordeaux) and Bezard (IMN- CNRS &Univ. Bordeaux). Each PI is a world leader in his field with a strong culture for interdisciplinarity, as evidenced by previous fruitful collaborations. Cognet-Groc (8 joint publications ~ 800 citations) and Groc-Bezard (3 joint recent publications), have already established tight collaborations, although this is the first time that the 3 expertises will be integrated in a common project. More generally, we believe that the expected findings of this project should go largely beyond the sole impact on the Parkinson disease. Indeed, it is known that ECS modifications also occur in other pathological disorders than Parkinson’s disease and also during neuronal communication, learning and aging where constant remodeling takes place. Our new methodologies should also be immediately transferable to other organ investigation (e.g. tumor development in oncology).

The oft-used statement that “the 21st century will depend as much on photonics as the 20th century depended on electronics” may be cliché, but the impact of photonics on human life is indisputable; Europe has even formally recognised the importance of photonics by naming it a Key Enabling Technology. Photonic related activities are essential for the competitiveness and industrial renewal. Among photonic technologies, lasers are crucial tools for a variety of applications. This project mainly focuses on the investigation high-power stable fibre-based lasers in continuous wave operation with only a single longitudinal mode, emitting quasi-monochromatic radiation with very narrow linewidth and low noise. This class of lasers has been thoroughly investigated in many aspects of fundamental research due to their competing applications in atom cooling, atomic clocks, laser spectroscopy, among other, but also in an ever increasing number of real-world applications (coherent LIDAR, holography, industrial instrumentation, high resolution spectroscopy……), where fine control of amplitude, frequency and phase is extremely important. Starlight+ is a fully-integrated Academia/Industry shared laboratory initiated in the fall 2014 between Azur Light Systems (ALS) and LP2N (http://www.lp2n.fr/starlightplus/?lang=en). ALS is a 6-year-old SME with 15 employees developing industrial/scientific and medical high-power fibre laser systems at new wavelengths. This joint photonics laboratory was founded after being selected by a competitive ANR program (ANR LabCom) and is strongly supported by the Conseil Régional Nouvelle Aquitaine (Recherche Nouvelle Aquitaine). Today, eight people (researchers, Ph.D. students, post-docs and engineers) work together in the LabCom to challenge the state of the art in high-power fibre lasers, taking advantage of the close proximity with ALS and its industrial expertise.The LabCom is financially supported by the ANR but also by the Cluster Laphia, the Labex First-TF and the Fonds Unique Interministériel (FUI). The scientific program of Starlight+ is organized around three main research themes: 1: Research and development of new stable laser systems based on MOPA fiber architectures in the spectral range from 976 – 1120 nm. 2: Development of systems for laser stabilization and frequency control, optimized specifically for fiber laser architectures. 3: Development of new architectures for agile lasers systems suitable for precise frequency sweeping in the visible and Deep Ultra Violet spectral regions using optimized resonant frequency conversion schemes. This new laboratory is housed within the Institute d’Optique d’Aquitaine facility. It benefits from close proximity to the technical center ALPhANOV which represents a major resource for industrial transfer and also proximity to the Institute of Optics Graduate School, both of which are housed in the same building. A parallel approach to the three main R&D themes has been implemented within an initial 3 year program. The first year of the program was dedicated principally to set-up and organization of the joint laboratory, the study of the fundamental properties in term of noise of optoelectronic seeding systems and applied to fiber amplifiers and the development of electronic and optical laser stabilization systems. The second and third years focus on the development of ultra-stable and tunable laser systems and innovative frequency conversion architectures. Beyond the initial 3-year period, the joint laboratory will be evolved towards a permanent structure, via public and private financing of research, development and industrialization activities.