Applications - idil mirror doctoral contracts

DOCTORAL SCHOOL SUBJECT: Sciences Chimie Balard

Lipid vesicles of plant origin: new vectors for
topical administration in chronic
inflammatory pathologies.

SUBJECT DOCTORAL SCHOOL : GAIA

Study of the potential of lipid vesicles of plant origin as new sources or vectors of natural antioxidants to combat lipid oxidation in food systems

Project summary:

Naturally produced by plants, lipid vesicles (pVLs) are of great interest, not only because of the large quantities available from various plant sources, but also because of their intrinsic biological properties. To date, most research on pVLs has focused on the biomedical sector.
The aim of this project is to explore the potential of pVLs to meet two major societal challenges: food and public health. In addition, this multi-disciplinary project, combining the fields of chemistry and health biology, takes an environmental approach, selecting plants mainly from the Mediterranean region and using eco-responsible protocols.

The two PhD students recruited will benefit from the specific expertise of each team (IGCM Dept Chimie Moléculaire and UMR Qualisud) and will first work together on validating the process for obtaining and characterizing pVLs. The pVLs obtained will then be evaluated as mirror images for the treatment of inflammatory skin pathologies such as psoriasis (Thesis 1) and as new antioxidant formulations to protect unsaturated lipids in foodstuffs from oxidation (Thesis 2).

In thesis 1, we aim to demonstrate that the intrinsic properties (antioxidant and anti-inflammatory) of pVLs, coupled with their ability to vectorize active ingredients, can improve the management of patients suffering from psoriasis by ensuring better diffusion through the epidermal layers to target areas affected by excess free radicals. As for thesis 2, its aim will be to show how pVLs can constitute a new source of natural antioxidants
ensuring ideal localization of the antioxidant in food emulsions in order to limit the diffusion of oxidation within a food.
Finally, these two theses will enable us to determine the best plant sources of pVLs for the two targeted applications and consequently propose new ways of valorizing various plant co-products from around the Mediterranean.

THESIS SUBJECT DOCTORAL SCHOOL EDEG

The contribution of frugal innovations in Brazilian family businesses to achieving sustainable development goals

THESIS SUBJECT DOCTORAL SCHOOL: I2S

The contribution of complex systems modeling to the analysis of compatibility between stakeholder viewpoints in sustainable development objectives

Project summary:

The aim of this project is to study the contribution of frugal innovations by Brazilian coffee family businesses to achieving sustainable development goals. To this end, it combines an analysis from a management science perspective with one from a complex systems modeling perspective. It identifies responsible innovation criteria for frugal family farms, constructs frugal family innovation scenarios, proposes a system representation methodology and provides an interdisciplinary analysis.
Recommendations for supporting stakeholders in frugal family innovations within a territory are expected at the end of the two theses.

This proposal is the result of a project combining teaching, research and sustainable action in the field. Associating France and Brazil, the proposal aims to contribute to the synergy of a more responsible production (in Brazil) and consumption (world market including France).
The two disciplines involved in the project work in synergy, each of the two theses being in a position to both receive and provide information and analysis to the mirror thesis.

THESIS SUBJECT DOCTORAL SCHOOL : I2S

Stochastic rainfall generators and impact studies on flood risk in Montpellier

THESIS SUBJECT DOCTORAL SCHOOL : GAIA

Neural network study of urban flood risk and the impact of extreme spatio-temporal rainfall events.

Project summary:

Floods are the number one natural hazard in France, with particularly severe impacts in urban and coastal areas. To improve our understanding and prediction of these extreme events, we are proposing several important extensions to the SW2D (Shallow water 2D) flow model, developed by the Inria-LEMON team in Montpellier. Firstly, we propose a high spatial and temporal resolution stochastic simulator for extreme precipitation forcing in urban and coastal environments (Topic 1). This precipitation is a forcing term for the flow models studied in the second thesis. Indeed, the second part of the project will involve applying a hydraulic model for simulating urban flooding, which will serve as a learning base for an artificial intelligence model enabling rapid estimation of flooded areas (Topic 2).

Next, we will develop spatialized sensitivity analysis methods to study how extreme values in the model's spatialized bivariate outputs (water heights and velocities) depend on the spatial patterns of extreme forcing. This impact study will be carried out at the intersection of the two thesis topics. The project aims to develop new generic methodological tools, as well as scenarios and maps of flood risk in the Montpellier region, taking into account the potential effects of climate change.

THESIS SUBJECT DOCTORAL SCHOOL : I2S

Development of a multi-well microelectrode microfluidic platform for in vitro stimulation and recording of human neuromuscular junctions

THESIS SUBJECT DOCTORAL SCHOOL : CBS2

Establishment of human neuromuscular junctions, both healthy and with SMA, to analyze electrical signatures and develop new therapies.

Motor neuron diseases such as SMA or ALS are rare disorders for which there are no effective treatments. These diseases mainly affect the neuromuscular junctions (NMJ), where information passes between motor neurons and muscle fibers. They cause severe mobility problems.

Project summary:

In order to study and understand the molecular mechanisms at work in these NMJs, it is essential to reconstruct them in vitro so that they can be observed under the microscope. If, in addition, we are able to stimulate and record electrical activity on both the neuron and muscle sides, then we have an extremely powerful tool for analyzing the functionality of NMJs.
This research project between biology and microengineering is based on a collaboration established between benoit Charlot from IES and Florence Rage from IGMM. After more than 5 years of collaboration, these two thesis partners have developed a first prototype of a multi-well platform (32 microfluidic chips on the same plate) instrumented (128 microelectrode channels) to reconstruct fully human NMJs derived from induced pluripotent stem cells.

The two PhD students will then embark on a large-scale measurement campaign using this first prototype, in which they will seed differentiated human NMJs, whether healthy or pathological. The aim will be to extract an electrical activity signature for each one. This signature will be used to assess the ability of an electrically stimulated motor neuron to transmit information to a muscle cell to induce contraction. This analysis will lead to the definition of a biomarker specific to NMJs, enabling us to study the effect of drugs on these NMJs.

These two thesis projects will be carried out in synergy, firstly on a vast experimental campaign to qualify the platform and then to evaluate the response of different NMJ models subjected to different active molecules. Then, in a second phase, the projects will evolve on both sides, the platform on the one hand, and the cellular model on the other, so that the microfluidic system can be adapted to the use and activity measurement of neuromuscular organoids or assemblies, which represent a more relevant evolution of the model, in the context of reduced testing on
animals.

DOCTORAL SCHOOL THESIS SUBJECT: Science Chimie Balard

Smart degrading nanoparticles for siRNA delivery using multi-dynamic peptide-based conjugates.

DOCTORAL SCHOOL THESIS TOPIC: CBS2

Targeting apoptosis and proliferation by siRNA in gastrointestinal stromal tumors as novel treatment.

Project summary:

A gastrointestinal stromal tumor (GIST) is a type of cancer that develops in the digestive system. GISTs are the result of known genetic mutations and, unfortunately, are increasingly resistant to conventional chemotherapy and radiotherapy. In this SMArt project, we will explore the use of siRNAs directed against proteins involved in GIST proliferation and apoptosis to develop an innovative therapy. We propose to generate intelligent vectors with different stimuli-reactive links between the nanoparticle and the grafts (PEG part and cancer-targeting sequence).

With this central interdisciplinary objective, the mirror theses proposed here will address two critical points: I) the design, synthesis and evaluation of smart siRNA vectors (PhD project 1, chemistry, partner 1), and II) the formulation of siRNA-loaded nanoparticles and evaluation on GIST cells and GIST tumor models (chick and mouse). (PhD project 2, biology, partner 2). The projects build on the solid experience and preliminary results of both partners in the field of gene delivery and gene therapy.

We expect major results in basic science on the fine control of chemical reactivity of peptide-based vectors through molecular design, as well as in pharmaceutical applications with the evaluation of a novel treatment for gastrointestinal stromal tumors. The project also has wider potential thanks to the modular design of the siRNA active ingredient, which should attract widespread interest.