Description du sujet de thèse

CONTEXT
In the context of chronic inflammatory bowel disease (IBD), unachieved resolution has been proposed as an immunologic cause. While resolution terminates inflammatory response, leading to hemostasis and tissue healing, unachieved resolution nests chronic inflammation that then turns out pathological. One critical step in the resolution process is the removal of apoptotic cells (AC) by macrophages, generating anti-inflammatory and reparative mediators. In IBD pathogenesis, neutrophils apoptosis and their attraction to the lesion is described deficient, limiting the initiation of the resolution. Pro-resolutive strategies are emerging and modify our view considering inflammatory disease treatment, shifting from inhibiting and depleting approaches to targeting reactivation of physiological patterns such as the resolution process promoting tissue regeneration.
One strategy would be to restore the resolution process through local supplementation with pro-resolving factors.
It is within this context that the ASPIRIN project is situated, with the objective of reactivating the resolution process at the site of intestinal lesions via the oral administration of "decoys" in order to regenerate the tissue. These "decoys" would consist of hybrid silica/liposome particles functionalized with serine or carrying serine derivatives.
OBJECTIVES
As part of the PhD project, fluorescent silica particles of several hundred nanometers with an organized porosity will be synthesized via a sol-gel process in the presence of structuring surfactants. Various formulations will be studied to adjust pore size in order to encapsulate molecules that may play a role in the inflammation resolution process.
A portion of the thesis will also focus on the incorporation of additives into the particle formulation to weaken the silica matrix and facilitate its biodegradation.
A study of the biodegradation kinetics of these porous particles will be conducted in simulated intestinal fluid, and the most promising candidates will be encapsulated in serine-functionalized liposomes to be evaluated on in vitro models of inflamed human tissue.

PROFILE
We are looking for a candidate with a background in chemistry or physical chemistry. Experience in synthetic chemistry or in the physical chemistry of dispersed systems would be appreciated. A strong interest in biological sciences would be also appreciated. A knowledge of most of the analytical tools that will be used during the PhD would be great : Thermogravimetric Analysis (TGA), FTIR and UV-Visible spectroscopy, Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM), X-Ray Diffraction (XRD), Dynamic Light Scattering (DLS), and Zeta potential measurements.

Contexte de travail

The PhD will take place at the Laboratoire Interdisciplinaire Carnot de Bourgogne (ICB), UMR 6303, CNRS - UBE (https://icb.cnrs.fr/) in Dijon, within the Adsorption on Porous Solids (ASP) team of the Interfaces Department. The thesis will be supervised by Drs. F. Bouyer and I. Bezverkhyy. This ANR-funded project also involves pharmacists and biologists from the UMR Right 1098 in Besançon, as well as organic chemists from the UTINAM Laboratory in Besançon.

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