Highlights of the 2023 theses

Investigation of the redox signaling involved in the chloroplast biogenesis

Laboratories : IBS and LPCV - 01/01/2021 – 31/12/2023


Abstract: The thesis investigated activity of the superoxide dismutases PAP4 and PAP9 from the PEP. The PEP envelope was calculated at 27,5 Å resolution, and the CSP41b 3D structure solved at 3.4 Å resolution. Its interaction with PRIN2 was investigated using biophysical experiments and tested in onion epidermal cells using bimolecular fluorescence complementation assay. For fishing PRIN2 interactors, a proximity labelling strategy was designed. Genetic constructions were cloned and tested in transient experiments, proving its feasibility. These studies are part of a broader project that aims at highlighting functional innovations in angiosperms around PEP-specific plastid transcription.
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Telomeric response to potentiate new theranostic approach in ratio-resistant lung cancer cells

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Laboratories : IAB and DCM - 01/10/2020 - 01/10/2023

PI : Virgine FAURE et Olivier RENAUDET      

Abstract Our project was to overcome radioresistance in lung cancer cells by combining radiotherapy with a theranostic system using radiosensitizing gold nanoclusters (AuNCs) able to deliver siRNA targeting TRF2 protein, one of the key players in telomeric radioprotective response.
Following the synthesis and characterization of the nanosystem, our results have shown that AuNCs were capable to interact with siRNA, to protect them and to deliver them efficiently into lung cancer cells. We demonstrated that this nanosystem increased significantly the radiosensitivity of lung cancer cells after X-rays exposure. Finally, the specific targeting of tumor cells was improved by modifying the surface of AuNCs in order to target GLUTs transporters, which are overexpressed in a wide variety of cancers.
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Design of cell-permeable and fluorogenic delivery agents to extend the spectrum of antibiotic action

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Laboratories :  DPM and IBS - 1/10/2019 – 09/02/2023

PI : Yung-SIng WONG and Eric FAUDRY   
PHD : Pascal MOSER   

Abstract: An important scientific need is to understand how a sufficient translocation of bioactive molecules across the Gram-negative cell wall can be assured. An original mean in this project was the use of cyclic peptides as carriers to improve antibiotics transport through the bacterial cell wall due to their remarkable mechanism of conformational changes (validated by computational modeling). Cyclic peptides, coupled with antibiotics, were synthesized in attempts to broaden the spectrum of antibiotics. We also designed a new promising self-immolative linker (SIL) aimed at delivering carboxylic antibiotics inside the bacteria. This was explored by the development of a selective redox-sensitive fluorogenic SILs to detect the release of carboxylic acids inside bacteria.

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Optimization of electrochemical transduction using aptamers for the detection of arginine vasopressin in the picomolar range

Laboratories : DCM and DPM - 01/10/2020 – 31/12/2023

PI : Michael HOLZINGER and Corinne RAVELET
PHD : Essohanam BEKE

Abstract: The detection of the hormone arginine vasopressin (AVP), an important biomarker for a series of diseases, needs currently expensive and time-consuming techniques. This project aimed to develop an electrochemical setup based on impedimetric transduction (EIS) using a specific aptamer (anti-AVP). One challenge was to determine the optimal immobilization strategy for reliable quantification of this hormone. Another was to decrease the limit of detection (LOD) down to the picomolar range. These targets could be implemented by establishing strict protocols for the formation of the sensing device.

The obtained results : A LOD in the sub-picomolar range was obtained with a linear range of four orders of magnitude.
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Impact of intermittent hypoxia on wound healing in experimental models of diabetic foot ulcers

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Laboratories : SyMMES and CIC - 01/01/2019 – 31/03/2023

PI : Matthieu ROUSTIT - Walid RACHIDI and Jean-Luc CRACOWSKI

Abstract: We hypothesised that microvascular dysfunction caused by intermittent hypoxia (IH) may potentiate diabetes-related impairment in wound healing. In healthy mice exposed to IH, we observed delayed healing of excisional ulcers, without impairment in skin perfusion or endothelium-dependent microvascular dysfunction. In diabetic mice, there was no additional impact of IH on wound healing, skin perfusion and reactivity. Peri-ulcer perfusion throughout the healing process, as well as neoangiogenesis, were also not impacted. We further tested this hypothesis in a patient-derived cellular model, with similar results.
In conclusion, our results suggest that chronic IH does not have deleterious additive effects on the cutaneous microcirculation in diabetes.
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Fighting oxidative stress thanks to nisod mimics

Laboratories : SyMMES and DCM - 01/10/2020 – 31/12/2023

PI : Pascale DELANGLE and Carole DUBOC 

Abstract: The objective of this thesis was to create biomimetic complexes inspired by the nickel superoxide dismutases’ (Ni-SOD) active site to replicate its efficient antioxidant activity. These complexes are based on a pseudo-ATCUN scaffold (Amino-Terminal CuII and NiII binding motif), capable of reproducing the NiII geometry in the enzyme's active site.

The obtained results have identified two reaction intermediates formed during the dismutation of superoxide by one of these complexes, providing valuable insights into the enzyme mechanism. Additionally, through the identification of factors enhancing SOD activity, highly efficient complexes have been developed, showing potential as antioxidant agents within cells.
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Published on  February 16, 2024
Updated on February 27, 2024