PhD (M/F) Dual stimuli-responsive infection-targeted pyrrolyldipyrrins for applications in photodynamic therapy

Job Description

Thesis Subject

The spread of microbial infections represents a menace to the humanity and its development. However, the increase of multidrug resistance limits the efficacy of many common antibiotics and antifungals. Photodynamic therapy (PDT) is a photochemistry-based medical treatment using the light at a specific wavelength, a photosensitizer (PS) and molecular oxygen. The absorption of the light by the PS produces the reactive oxygen species (ROS), including singlet oxygen, both causing cell death followed by an inflammatory and immune response. Nowadays, the PDT as antimicrobial treatment (or photodynamic inactivation, PDI) is a promising strategy to fight this thread because the lack of specific targets, which reduces the development of resistance.

Our laboratory proposes the synthesis of novel dipyrrin-based PS, which will be designed to be dual stimuli-responsive and directed specifically against a large panel of microbes. The selected scaffold is inspired by the natural product prodigiosin, which is a red pigmented bacterial second metabolite. While its applications as immunosuppressive, antimicrobial and anticancer agent have been limited due to the high selectivity towards healthy cells, the tripyrrolic synthetic analogues have been shown to maintain the therapeutic activity of the parent compound yet with improved selectivity towards the targeted cells. The versatility of this basic structure has made it possible to modify it and gain a comprehensive understanding of the structure-activity relationship of these compounds. Despite the structural similarity to well-known potential PS, very little is known on the photophysical properties of this scaffold except for those of their corresponding boron (mainly -BF2) or transition metal complexes (tin, copper, zinc, cobalt).

The objective of this PhD thesis will be:
1) the synthesis of novel prodigiosin-inspired PS bearing different functionalization on the aromatic scaffold and the measurement of the photophysical properties of each derivative;
2) the functionalization of the most promising candidate from the previous screening to make it responsive to both the glutathione and acidic pH;
3) the conjugation of the dual responsive PS to a directing moiety which will increase the selectivity towards the microbial surface.

The project has already received the necessary funding from the ANR JCJC (SPOTIACT).

Your Work Environment

The Institute of Chemistry and Processes for Energy, the Environment and Health (ICPEES) is a joint research unit jointly supervised by the CNRS and the University of Strasbourg (UMR7515). Its staff comprises around 50 permanent members and approximately 80 PhD students, postdoctoral researchers and other fixed-term contract staff. This PhD will be carried out within the Organic Chemistry for Materials, Biology and Optics (COMBO) team, led by Dr Gilles ULRICH. The COMBO team is based at the Strasbourg School of Chemistry (ECPM) of the University of Strasbourg (Unistra, University of Excellence), within the Department of Molecular and Analytical Chemistry at the ICPEES.

We are seeking a highly motivated candidate with a strong background in organic chemistry and synthesis, and a willingness to learn various spectroscopy and electrochemistry techniques.

Please attach your final Master's grades to your CV or cover letter.

Doctoral school n°222

Working conditions: - Easy access to the Cronenbourg campus by public transport - Possibility of partial reimbursement of travel costs by the CNRS - Option to dine at a university canteen on the Cronenbourg campus with meal subsidies provided by the CNRS.

Compensation and benefits

Compensation

2300 € gross monthly

Annual leave and RTT

44 jours

Remote Working practice and compensation

Pratique et indemnisation du TT

Transport

Prise en charge à 75% du coût et forfait mobilité durable jusqu’à 300€

About the offer

About the CNRS

The CNRS is a major player in fundamental research on a global scale. The CNRS is the only French organization active in all scientific fields. Its unique position as a multi-specialist allows it to bring together different disciplines to address the most important challenges of the contemporary world, in connection with the actors of change.

CNRS

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