Ott Scheler

Reproduction is regulated by the endocrine system and its disturbances by endocrine disruptive chemicals (EDCs) may lead to infertility. As humans are constantly exposed to EDCs through the use of common household items and personal care products, it is important to test chemicals for their potential activity as endocrine disruptors affecting reproductive function. Project MERLON aims to study the effects of EDCs on sexual development and function in order to deliver new approach methodologies (NAMs) for EDC identification. While MERLON targets the vulnerable stages of development from fetal to puberty, MERLON2, with additional partner TalTech, will add one more sensitive window of susceptibility in female reproduction to the project: the adult preovulatory ovarian follicle, where the oocyte maturation takes place. In collaboration with TalTech, it was recently demonstrated that follicular somatic cells (FSCs) lose sensitivity to follicle stimulating hormone (FSH) in the presence of a mixture of 13 EDCs. FSH is crucial for both, the oocyte maturation and for the synthesis of steroid hormones by the FSCs. We have also demonstrated the intricate heterogeneity of somatic cells in the ovarian follicle. The roles that FSC subpopulations play in the adverse effects of EDCs is unknown and unaddressed by the initial MERLON project. MERLON2 will complement the aims of the consortium by developing NAMs based on single cell transcriptomics, automated image analysis and machine learning to understand the effect of EDCs on FSC subpopulations and their sensitivity to FSH. This will increase the research output for MERLON in the number of proposed NAMs and quantitative adverse outcome pathways. As a result of MERLON2 the range of stakeholders will enlarge, increasing the public awareness related to the harmful health effects of EDCs, and proposing new approaches to resolve the complicates issue of testing substances in everyday products for their adverse effects on human fertility.

The overall objective of the original CHIRALFORCE project is to demonstrate enantiomer separation in a compact, on-chip, photonic platform that is fabricated using standard silicon-based technology. This CHIRALFORCE2 hop-on project enhances the original project by providing automated in-line platform for the analysis of chiral separation for this CHIRALFORCE photonic chip. Separation of enantiomers from mixtures is essential, especially in early phase drug discovery processes when many mixtures need to be separated. CHIRALFORCE aims to revolutionize the field of chiral chemistry by introducing a radically new strategy for separating enantiomers by using chiral optical forces in silicon-based photonic integrated waveguides to separate enantiomers. The successful implementation of CHIRALFORCE project (development of separator chip) relies on fast and accurate feedback on the enantiomer separation. However, current state-of-the art technologies for checking the enantiomer separation: e.g. circular dichroism (CD) spectroscopy or High-Performance Liquid Chromatography (HPLC) lack off-the shelf capabilities for rapid in-line separation monitoring that is needed in CHIRALFORCE project. CHIRALFORCE2 addresses this need by providing a platform for in-line monitoring of the chiral separation down-stream from the CHIRALFORCE separator chip. We use interdisciplinary approach combining automation, electronics, optics and IT disciplines. The monitoring of in-line chiral separation will be achieved by CD-spectrometry or absorbance detection depending on the microfluidic and optical requirements from CHIRALFORCE project. Both scenarios are supported by designated software for the signal analysis and feedback.