BIORIMA stands for Biomaterial Risk Management. BIORIMA aims to develop an integrated risk management (IRM) framework for nano-biomaterials (NBM) used in Advanced Therapeutic Medicinal Products (ATMP) and Medical Devices (MD). The BIORIMA RM framework is a structure upon which the validated tools and methods for materials, exposure, hazard and risk identification/assessment and management are allocated plus a rationale for selecting and using them to manage and reduce the risk for specific NBM used in ATMP and MD. Specifically, the IRM framework will consist of: (i) Risk Management strategies and systems, based on validated methodologies, tools, and guidance, for monitoring and reducing the risks together with methods for evaluating them; (ii) Validated methodologies and tools to identify the potential Exposure and Hazard posed by NBM to humans and the environment; (iii) A strategy for Intelligent Testing (ITS) and Tiered Risk Assessment for NBM used in ATMP and MD. BIORIMA workplan consists of 7 workpackages covering the major themes: Materials, Exposure, Hazard and Risk. BIORIMA will generate methods and tools for these themes for use in risk evaluation and reduction. The BIORIMA toolbox will consist of validated methods/tools for materials synthesis; reference materials bank; methods for human/environment exposure assessment and monitoring; (eco)-toxicology testing protocols; methods for prevention of accidental risks – massive release or explosion – A tiered risk assessment method for humans/environment; An intelligent testing strategy for NBM and risk reduction measures, including the safer-by-design approach. BIORIMA will deliver a web-based Decision Support System to help users, especially SME, evaluate the risk/benefit profile of their NBM products and help to shorten the time to market for NBM products.

The purpose of SURFANICOL project is to study the structure and dynamics of anisotropic particles at interfaces and in particular the manifestation of the coupling between the rotational and translational degrees of freedom on the motion of individual particles and on the phase behavior of concentrate systems. The project involves a team of physicists and physical chemists of Montpellier and a team of physicists from Hong Kong. Both teams share expertise in hydrodynamics and each is distinguished by expertise in nanotechnology for Hong Kong and in optics and physical chemistry for Montpellier. Many industrial processes are based on the trapping of solid particles at fluid interfaces: including stabilization of emulsions in food and pharmaceutical, flotation applied to wastewater treatments and separation of minerals industries. The optimization of these processes is based on a better understanding of individual and collective behavior of the particles, but so far, academic interest has focused on spherical particles. The first part of the project will be devoted to the study of individual particle. We expect an enhancement of the translation-rotation coupling when the particles are trapped at interfaces and will pay a particular attention to the passage of the particle from solution to the interface, when solid friction of the triple line add gradually to viscous forces. The use of active colloids, i.e. propelled through a surface catalyzed reaction, will offer a new way to control this coupling, since the power supplied by the reaction depends on the orientation of the particle, which is subject to thermal fluctuations. In the second part of the project we will study the role of translation- rotation coupling in the structure and dynamics of two-dimensional concentrated phases as nematic, hexatic, and glass. To moderate capillary interaction we will design low surface tension interfaces, playing on the proximity of the critical point of immiscible blends. The use of active colloids will also allow to overcome the kinetic barriers induced by capillary forces. The project consists of several tasks the first of which will be the preparation of particles and interfaces suitable for the proposed studies. In the second task holographic detection coupled with multi-traps optical tweezers, which will be developed in the Montpellier, will allow to reveal the dynamical approach of particles to the interfaces, until trapping. These measurements will be combined with force measurements on single particles developed in Hong Kong from an atomic force microscope. Finally, phase transitions in two dimensions will be observed by video microscopy, with image processing at single-particle resolution to get a unique knowledge of these systems. The expertise exchange will be facilitated by the exchange of two jointly supervised PhD students co-funded by ANR and RGC.

Over the last few decades, anomalous diffusion processes, in which the mean squares particle displacement does not grow linearly with time, have been observed in a wide variety of practical applications. Mathematically, these physical processes are described by generalized time-fractional partial differential equations (PDEs), involving generalized (nonlocal) time fractional derivatives. In these models, there are several crucial physical parameters, e.g., diffusion coefficient, source and order, that are not directly measurable and instead have to be estimated from indirect observations of the solutions to the PDEs. This leads to a wide variety of parameter identification problems of estimating physical parameters in the mathematical models. Due to their enormous practical significance, it represents one of the most actively researched areas in mathematics. This class of problems is mathematically and numerically very challenging due to a lack of well-posedness in terms of existence, uniqueness and continuous dependence on the problem data, and the inevitable presence of noise in the observational data. Due to the high complexity of relevant mathematical models, there are many open questions in the mathematical theory and numerical simulation that have held them back from wider adoption. Thus, there is an imperative need to address these outstanding mathematical and numerical challenges, especially unique and stable determination and robust reconstruction algorithms. This issue is particularly challenging for the generalized diffusion models, since their solution theory is only poorly developed. Indeed, the nonlocality of the generalized derivative and the presence of nonlinear term make inapplicable many crucial tools, such as e.g., product rule, Laplace transform, and integration by part, and limited smoothing properties of solution operators preclude a straightforward development of the numerical approximations. This project consists of five work packages, covering singular sources, recovery of nonlinear terms, variable order model, stability estimates via transformation, and tools for practical inversion. All these packages aim at addressing different challenges associated with parameter identifications for anomalous diffusion from both mathematical and numerical perspectives, via a synergy of the expertise of French and Hong Kong teams. The project outputs will provide the much needed analytic and numerical insights into anomalous diffusion processes.

Somatic stem cells (adult stem cells) are essential for homeostatic maintenance of various tissues. In addition to normal homeostasis, they are also involved in tissue regeneration in case of injury. Interestingly, adult stem cell function declines with age and this phenomenon limits tissue regeneration in aged tissues. To understand the molecular basis of the functional decline in aged stem cells, we will investigate how canonical Wnt signaling is involved to regulate cell fate decisions in tissue homeostasis and repair. We are using muscle stem cells (MuSCs) as a model stem cell system, our preliminary data suggests that an adequate intrinsic level of ß-Catenin, the main effector of canonical Wnt signaling, is required for MuSC function during muscle regeneration. We thus began to examine how Wnt/ß-Catenin signaling functions as a pleiotropic pathway to regulate both myogenic differentiation and cell fate decisions. Accumulated evidence has suggested that rejuvenation of aged stem cell populations can be performed and that such mechanism can be controlled in an epigenetic fashion. However, the extent to how this cellular reprogramming event works is unclear. Wnt signals are a key sources of cues that direct myogenic lineage progression and it has also been implicated in promoting MuSC to adapt an alternative fate in aged muscle, rendering MuSC dysfunctional and resulting in an impairment of muscle regeneration in aged animals. We thus propose to understand the molecular and epigenetic regulation of canonical Wnt signaling in MuSCs during organismal ageing. Our project aims to decipher the role(s) of canonical Wnt/ß-Catenin in MuSCs cell fate decisions during ageing. Using Cre/Lox genetic approaches, we will first assess and compare the implication of ß-Catenin in young and old MuSCs function. As aged MuSCs can be rejuvenated and thus appear not genetically altered, we will then focus on understanding the age-related changes in epigenetic determinants in MuSCs, and whether canonical Wnt signaling is differentially controlling asymmetric divisions of young and old MuSCs. This project is lead by an interdisciplinary consortium comprises of researchers in France and Hong Kong studying molecular regulation of stem cell function. Members of this consortium have complementary expertise in the area of stem cell biology, computational biology and genetics. It is expected our study will contribute to the understanding of MuSC fate during normal ageing. We strongly believe this proposal will provide new insights as to the molecular mechanisms that regulate stem cell ageing. The result of this proposal will lead to the identification of new selective targets for the development of therapy for stem cell rejuvenation.