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PhD position in Chemistry at the interface of synthesis / biology for the development of anticancer theranostic compounds (fully funded, M/F)

This offer is available in the following languages:
Français - Anglais

Date Limite Candidature : lundi 30 mai 2022

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General information

Reference : UMR5306-GUIBOR-002
Workplace : ORSAY
Date of publication : Monday, May 9, 2022
Scientific Responsible name : Guillaume Bort
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 5 September 2022
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly

Description of the thesis topic

Mission

The possibility to control the activation of treatment in space and time in vivo has mobilized considerable efforts in the last 20 years. Externally triggered theranostic prodrugs are one of the most promising tools in this field. In particular, photosensitive prodrugs and nanoobjects showed great promise for spatio-temporally controlled and non-invasive activations in vivo. However, to date, most of the photosensitive systems described can only be activated by UV to near-IR lights. This limits in vivo activation to few millimetres below the skin, which hugely restrains clinical applications, mainly to ophthalmology or skin treatment. To date, there is no non-invasive approach for using light-sensitive materials in deep tissues.
The project takes part in the development of tools able to provide treatment in deep tissues in a space- and time-controlled resolution. Theranostic prodrugs detectable by nuclear magnetic resonance imaging (MRI) and able to be activated by radiotherapy clinical beams, will be developed. This project, based on activation techniques relying on already-available clinical infrastructures, is consistent within the perspective of future developments of molecular systems for clinical applications. The chemical (prodrug synthesis), physical (activation mechanism) and biological (cell-death mechanism, therapeutic effect) locks will be investigated in collaboration with Institut Curie (Paris, Orsay), Institute of Light and Matter (Villeurbanne) and Laboratory of Chemoinformatics (Strasbourg). The PhD candidate will be based at the Institut Curie (Orsay) in the laboratory “Chemistry and Modelling for Biology of Cancer” and in the team “Chemistry and Modelling for Protein Recognition”. She/He will be supervised by Dr Guillaume Bort.


Job description

The project consists in the development of theranostic prodrugs for cancer treatment, adapted for MRI monitoring and for activation upon radiotherapy. Both physical and biological mechanisms leading to prodrug activation and cell toxicity respectively, will be investigated.
In addition to organic and inorganic synthetic chemistry, other techniques will be acquired such as cell biology, fluorescence microscopy, flow cytometry and characterisation upon radiation. The PhD candidate will also be involved in other activities related to this project and supported by collaborations such as density functional theory calculation, development of algorithm for machine-learning and data analysis.

Developed skills :
- Synthesis of theranostic prodrug using organic and inorganic chemistry.
- Prodrug activation and assessment of photophysical properties.
- Investigation of stability/activation/diffusion in biological environments, cytotoxicity and immunogenicity.
- Bringing forward ambitious and realistic design of new compounds, synthesis pathways, characterization techniques; being proactive.
- Participation in the supervision of engineers and trainees.
- Restoring the results to collaborators and communication at international conferences, participation in writing of scientific manuscripts.


Required Skills

You should hold a master's degree in chemistry. We are seeking a motivated individual with a desire to tackle technical and scientific problems to potentially make breakthrough innovation in medical treatments, and with a strong interest in multidisciplinary approach. English oral communication skills and a great team spirit are a must.
This project will give great opportunities to develop competences in organic/inorganic chemistry, physics of radiations, cell biology and associated characterization techniques. You are expected to be highly motivated to take advantages to work in a leading research environment, to benefit from a multi-collaboration context, and to potentially participate in the valorisation phases (patent, etc.) of this project.

Work Context

The position is administratively attached to the Institute of Light and Matter (Institut Lumière Matière - iLM) in Villeurbanne and the experimental work will be carried out at the Institut Curie in Orsay.
iLM is a joint CNRS-University of Lyon 1 research unit located on the Lyon Tech La Doua campus. With approximately 300 employees, including a hundred doctoral students, iLM is a major player in physics and chemistry research in the Auvergne Rhône Alpes region, internationally recognized for the excellence of its research. Fundamental research, responses to major societal challenges and innovation are at the heart of the unit's approach.
A leading player in the fight against cancer, Institut Curie brings together an internationally-renowned Research Center and an advanced Hospital Group that provides care for all types of cancer. Founded in 1909 by Marie Curie, Institut Curie comprises three sites (Paris, Saint-Cloud and Orsay), where more than 3,500 members of staff are dedicated to achieving three objectives: hospital care, scientific research, and the sharing of knowledge and the preservation of legacy. As a private foundation that is recognized as serving the public interest, Institut Curie is supported by donations and grants. This support is used to fund discoveries that will improve treatments and the quality of life of cancer patients. The successful candidate will benefit of a vibrant environment based on the pluri-disciplinary approaches and excellence offered by over 85 research groups constituting the Institut Curie.
The project related to this position is currently supported by several collaborations gathering different expertizes such as molecular observation at the attosecond-timescale resolution using ultrafast spectroscopy, in vitro and in vivo assessment of immunogenicity and therapeutic effect, and development of machine-learning algorithms and density functional theory models. The PhD candidate will be at the interface of all these approaches and will have some opportunities to take part in several collaborative studies.

Constraints and risks

No specific risk. Chemical and biological products will be handled with appropriate safeguards. Traveling between Villeurbanne and Orsay may be possible.

Additional Information

The starting date can potentially be modified depending on candidate availability.

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