Growing evidence indicates that lifespan human chronic exposure to multiple chemical contaminants present in the environment (including food, water, air and soil) can interfere with the normal function of the endocrine system, and consequently induce adverse health effects on an intact organism and on its progeny. To date, endocrine-disrupting chemicals (EDCs) are suspected or proved to be involved in the development of hormone-sensitive cancers and dysfunctions related to the immune or reproductive systems. According to national recommendations and legislation, and based on current biomonitoring approaches, the number of analyzed EDCs remains limited to known classes of molecules which are furthermore investigated in few matrices. Therefore, the current knowledge is only partially reflecting the actual human chemical exposome.
The development of high throughput analytical strategies dedicated to the detection and the characterization of emerging, still unknown EDCs present at ultra-low doses in complex matrices such as food, or biological sample remains a methodological challenge and a major concern for public authorities.
In this project, we propose to develop a non-targeted strategy allowing the detection and the characterization of EDCs (emerging and/or not yet known) from complex matrices. The work will be focused on currently blocking steps in relation with both complex sample preparation and analysis issues, including the purification and fractionation steps to reduce the complexity of the mixture and the semi-targeted monitoring of molecules exhibiting specific biological activity, which constitutes the originality of the present work.
- The first phase will consist in validating purification efficiency and developing a new multi-step fractionation process using High-Performance Liquid Chromatography (HPLC).
- In the second phase, we will analyze the fractions obtained using gene reporter assay based on ligand-receptor response (e.g. AhR, which is a critical intermediate in the toxic and carcinogenic response or others).
- The third and last phase will focus on the characterization of the biologically active fractions and the elucidation of the structure of isolated molecule by means of mass spectrometry and by a bioinformatics approach designed to reveal specific isotopic patterns and exact mass.
The overall procedure will overcome several issues currently limiting isolation and identification of a biologically active emerging and/or not yet known EDCs from a complex matrix and could answer needs high throughput work. The multi-step fractionation will reduce the number of compounds in the same fraction and reduce matrix effect. Finally, gene reporter assay will confirm biological activity of the isolated compound and mass spectrometry will enable its characterization.
Fanny RENOIS, Dr (LABERCA)
Gaud DERVILLY-PINEL, Dr, HDR (LABERCA)
We are looking for a highly motivated scientist with M2 or PhD degree.
- Strong chemical background with a PhD in Chemistry, Analytical Chemistry or equivalent
- Strong hands on experience with:
- Purification and fractionation techniques
- Structural elucidation using mass spectrometry (tandem and/or high resolution MS) and/or NMR
- Good laboratory skills
- Good collaboration and communication skills (written and oral English)
- Structured and analytical working approach
The period of employment is 1 year, salary depending on experience.
For further information, please contact the project coordinator, Dr Fanny RENOIS (email@example.com).
Please submit your application no later than 15th August 2017.
Applications must be submitted as one pdf file containing all materials to be given consideration. The file must include:
- A letter motivating the application (cover letter)
- Curriculum vitae
- 1 or 2 letters of support
- M2 or PhD diploma