Joint research activities
One of the key aims of the TEAMING project is to transform the RECETOX Research Centre into the Centre of Excellence in the Environmental Health Sciences. Achieving the excellence in environmental science is the paramount of RECETOX. Thanks to our advanced partners, we are building the complementary scientific expertise.
Selected joint projects
Human exposome
The human exposome research benefits from the collaboration of all project partners and research infrastructures namely at RECETOX and BBMRI. The collaboration with ETH is focused on the interpretation of data from the international air monitoring networks. ETH also supports the UCL epidemiologists, and RECETOX Environmental Health programme in development of the GIS-based modelling of the air-quality impact on public health. Within the functional exposomics we work on the application of the high-resolution MS techniques for target assessment and non- target screening of anthropogenic chemicals, metabolic and/or protein effect markers. One of the the greatest achievement is the development of open-access capacitiessuch as data processing pipelines available to public through the Galaxy pipelines of ELIXIR or annotated MS libraries.
Pharmacokinetic modelling
The research in pharmacokinetic modelling is realized within the group jointly co-supervised by researchers from RECETOX and the ETH. It is filling the gap in modelling capacities of the RECETOX. The research isfocused on the management, harmonization, analysis and interpretation of biomonitoring data, which is overseen by dr. Klára Komprdová, and on environmental and human exposure assessment, environmental persistence and long-range transport of organic chemicals, chemical risk and hazard assessment and development of specific human pharmacokinetic models, which is overseen by prof. Martin Scheringer.
Integrative toxicological risk assessment
We focus on mechanistic toxicological research on integrative networks of Adverse Outcome Pathways (AOPs) for metabolic and endocrine disruption. This is being explored using case studies with novel organophosphate flame retardants (nOPFRs). The research resulted in novel review of nOPFRs endocrine disrupting potential towards nuclear receptors and reproductive outcomes (published in Top 10% journal Env International; https://doi.org/10.1016/j.envint.2021.106550), and demonstrated development of AOPs for hepatic steatosis and Nonalcoholic Fatty Liver Disease (NAFLD; two published studies). Within this main direction of our research we foresee closer collaboration with Teaming project partner ETH - Prof. Dr. Shana Sturla.
Environmental Health
The research activities within this research programme are realized in close collaboration with the UCL partners and also in connection to the ERA Chair project RECETOX is implementing currently. It allows to develop the epidemiological expertise, which was missing for years and which has become very important in the time of the COVID pandemics. Moreover, several other studies were realized, such as the impact of the COVID pandemic on job loss and health care utilization among older persons in Europe, risk factors of alcohol consumption in the existing ELSPAC study, respiratory functions in the HAPIEE cohort (ageing cohort) or the large study of COVID-19 antibodies in the Czech Republic.
Exposure and health risk assessment
The research activities of this research group benefits from the partnership with the UCL epidemiologists. For now, the focus is on the assessment of potential relationship between external exposure (AQ – air quality parameters, like PM10, PM2.5, NO2, SO2, O3) and selected health outcomes in population studies (pulmonary diseases - asthma, bronchitis, etc.) in exposome approach and dentification of suitable biomarkers of effects and biomarkers of exposure (internal exposure) together with the other exposome factors that can modify such biological effect in response to the environmental exposures in selected cohort studies.
Chemical tools for diagnosis and therapy
In the current project of the Organic Photochemistry team, photochemistry of naturally occurring as well as synthetically prepared (modified) flavonoids as potential photoCORMs are studied in detail to understand the basic structure-reactivity principles. The compounds with the most suitable properties and in vivo potential are being tested for biomedicinal use as photoCORMs. These activities are realized both within the internal and external cooperation, namely with the ETH research group of prof. Andrew de Mello.
Alzheimer disease study: on-chip formation of liposomes as membrane models
In collaboration with the ETH team, we have developed a microfluidic device for the reproducible formation of unilamellar monodisperse liposomes, ideal membrane models to study β- amyloid (Aβ) peptides in close to physiological conditions. We follow one of the main hypotheses that stipulates that the most toxic Aβ42 peptide disrupts neuronal plasma membranes by creating pore- forming oligomers. For this purpose, we have developed the leakage assay for high-throughput monitoring of this toxicity towards biological membranes. The assay will be further optimized, validated and tested in on-chip format. In the following period, this novel technology will be employed in elucidating the structural basis of Aβ42 oligomerisation in the physiological environment of neural membranes and deciphering the role of lipid membranes composition.
Development of therapeutics for Stroke treatment: on-chip analysis of thrombolytics
During the research visit of Martin Toul at ETH Zurich, the new advanced microfluidic platform for combinatorial screening of thrombolytic drugs was utilized for systematic analysis of thrombolytics. In this project, the initial prototype was further optimized to ensure robust operation and reproducibility of the biochemical analysis. The novel more effective fabrication method was developed for chip production. Subsequently, the device has been applied to monitor the reaction kinetics and inhibitory characteristics of selected enzymes: alteplase, tenecteplase, urokinase and desmoteplase. The project is still actively running in both ETH and RECETOX.
Database Mining: Integration of Bioinformatics and High-Throughput Microfluidics
We have implemented novel droplet-based devices, developed in the previous period in collaboration with ETH team, into a pipeline for high-throughput mining of novel proteins and enzymes from gene databases. The pipeline integrates automated in silico analysis (software EnzymeMiner, https://loschmidt.chemi.muni.cz/enzymeminer/) with high-throughput microfluidics. Microfluidics accelerates experimental testing up to 20,000 reactions per day while achieving 1,000-fold lower protein/enzyme consumption. This methodology resulted in doubling the “toolbox" of the model enzyme family (haloalkane dehalogenases) characterized over three decades, yielding novel variants surpassing the efficiency of currently available enzymes. Combining microfluidics with modern global data analysis provided precious mechanistic information related to the high catalytic efficiency of newly identified variants. This pipeline applied to other enzyme families can accelerate the identification of enzymes and proteins for biomedical and industrial applications as well as the collection of high-quality data for machine learning.
