Reference : UMR8612-MYRTAV0-002
Workplace : CHATENAY MALABRY
Date of publication : Tuesday, July 26, 2022
Scientific Responsible name : Myriam taverna
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 1 October 2022
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly
Description of the thesis topic
Type II diabetes and associated cardiovascular risks are considered major public health issues. Type II diabetes could be related to the aggregation of the human amyloid peptide (hIAPP or amylin) and its deposition in the pancreatic β cells, leading to their degeneration. Currently, there is no treatment to prevent the formation and deposition of these hIAPP oligomers in pancreatic cells. In this context, the Ph.D candidate will be involved in the development of an innovative polymeric nanomaterial (NM), so-called « Janus » with two faces, one allowing the in vivo capture of hIAPP and its circulating oligomers, and the other the binding of human serum albumin (HSA) for prolonged circulation in the blood.
Therefore, this thesis aims at; (i) characterizing the interactions of this nanomaterial functionalized by ligands able to bind hIAPP selectively, with hIAPP, its oligomers and HSA using different complementary techniques available at IGPS and IPCM (such as Isothermal Titration Calorimetry, circular dichroism spectroscopy, zeta potential measurements, electron microscopy,…..), (ii) predicting NM's behavior in vivo, by studying the interactions that can be established in a complex biological medium such as blood, (iii) evaluating their biological behaviors (culture cells and in vivo). For this purpose, the doctoral student will characterize the interactions of the nanomaterials with hIAPP and HSA in biological fluids. The influence of blood proteins will be also investigated. The second part of the Ph.D. will be dedicated to biological and in vivo experiments (i.e. cytotoxicity, biodistribution, and pharmacokinetic studies). The PhD will benefit from different t platforms (circular dichroism, HPLC-MS, etc.) located at the faculty of pharmacy and from the multi-disciplinary skills of the collaboration (ANR JAROD) in terms of chemistry, physicochemistry, and biology.
The Ph.D thesis will be performed at the Institut Galien Paris Saclay UMR CNRS 8612
Constraints and risks
No risk identified
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