Projects

Abstract

Ion mobility-high resolution mass spectrometry (IM-HRMS) is the next-generation analytical platform in research and industry. Unlocking its full potential across applications as varied as biotherapeutics, environment and food safety requires not only pushing back the frontiers of instrumentation, fundamental understanding and applications – but harmonisation is essential. To achieve this, current shortcomings in data collection, analysis and reporting across instrument types, laboratories and research areas need to be scrutinised and overcome. The MobiliTraIN Doctoral Network will form 10 Doctoral Candidates(DCs) who will bring a new fundamental understanding of IM-HRMS, provide reference materials and guidelines for standardisation, develop state-of-the-art methods for the application of IM HRMS in biopharmaceutical development, biological 'omics studies, and nontarget screening of contaminants, and lay the foundations for IM-HRMS adoption in industry. Through an interdisciplinary research programme, including an open science approach and training in technical, business and transferable skills, the MobiliTraIN DCs will become leading experts in ion mobility with a unique skill set to successfully advance their careers while supporting Europe's innovation capacity. Building on existing collaborations and research excellence covering the entire innovation chain of IM-HRMS development and application, MobiliTraIN unites 8 academic institutions, 3 leading instrumentation companies, 1 regulatory agency, 1 pharma industry leader and 5 SMEs from 8 countries. With complementary expertise, know-how and mentoring experience, our consortium is ideally suited to unveil the potential of IM-HRMS as a key technology for safer therapeutics, better understanding of complex disease progression and improved monitoring of food, water and public health safety

Researcher(s): Promoter: Covaci Adrian, Co-promoter: van Nuijs Alexander

Research team(s) Toxicological Centre

Abstract

Belgian and European citizens are exposed to multiple environmental stressors, such as chemical pollution, noise or lack of green space. The actual PFAS crisis in Flanders illustrates the urgent need for scientific evidence to shape environment & health policy making. EIRENE-Flanders is the Belgian hub of EIRENE RI, the European Environmental Exposure Assessment Research Infrastructure. In line with the holistic 'exposome' approach, it will allow to capture the complex interactions between environmental exposure, lifestyle and socio-economic variables, their impact on biological processes in the human body and effects on human health. It provides the infrastructure for large scale collection of human samples and data, efficient measurements of large sets of chemicals, metabolites and proteins, connection to existing datasets, and use of advanced bioinformatics and data science methods to process these large amounts of data. EIRENE-Flanders will contribute to reduce the environmental burden of disease through scientific evidence for environmental, chemicals, food safety and preventive health policies both at Flemish and at European level, and personalised medicine approaches.

Researcher(s): Promoter: Covaci Adrian, Co-promoter: Jorens Philippe

Research team(s): Toxicological Centre

Abstract

Per- and polyfluoroalkyl substances (PFAS) are chemicals globally present in the environment and biota, as a result of their massive production and use in numerous applications, such as food contact paper, fire-fighting foams, textiles, construction and cleaning products. Their bioaccumulative and persistent properties have led to global regulatory measures for PFOS and PFOA. These are the most frequently detected legacy PFAS and their concentrations are still very high in the environment and biota. In addition, there are many emerging PFAS alternatives developed, with similar structures and chemical properties, not yet regulated and hence used unrestrictedly. However, very little or no information is available on the bioavailability, biomagnification and toxic effects of these emerging compounds, particularly for the terrestrial environment. PFAS may thus accumulate in the environment, posing risks to organisms. There are also many uncertainties on which factors might influence the bioavailability and biomagnification, especially of emerging PFAS. The identification of emerging PFAS, which have largely replaced the legacy PFAS, would allow us to investigate the environmental relevance of currently-used PFAS, as well as to characterize possible point sources. Detailed field studies on soil, plants, invertebrates (e.g. earthworms, woodlice, caterpillars, snails, slugs, and spiders), and great tits (Parus major; a songbird model species) planned in this project will provide us with: 1) an overview of the distribution of legacy and emerging PFAS present in the terrestrial environment near a fluorochemical polluting hotspot in Antwerp, 2) how the concentrations in the food chain are influenced by soil properties, and 3) their potential toxicity in key model species. In addition, experimental lab studies with PFAS and elevated temperature (T) as stressors on terrestrial invertebrates and plants will be performed to: 4) disentangle causal links from confounding effects regarding the soil properties, 5) verify whether or not increased T and PFAS have an additive toxic effect when combined, and 6) create a mechanistic framework explaining the underlying subcellular basis of root growth responses towards PFAS/increased T in the plant model species Arabidopsis thaliana. This project will allow us to understand the bioavailability and mechanism of the toxicity of emerging and legacy PFAS in plants, invertebrates, and birds and will offer instruments for regulators to assess the environmental risk and potential effects on human health.

Researcher(s): Promoter: Bervoets Lieven, Co-promoter: Covaci Adrian, Eens Marcel, Prinsen Els, Vissenberg Kris

Research team(s): Ecosphere

Abstract

FoodTraNet is designed to provide high-level training of a new generation of high achieving early stage researchers (ESRs) in a common platform of advanced mass spectrometry tools for food quality, safety and security. Due to the fast growing and changing area in food science researchers need a multidisciplinary, intersectoral grounding in these tools to extract all the potential from traditional and new available methodologies and techniques. Although already available there is still a big gap between research capability and industrial uptake that needs to be bridged to assure their use in more practical and efficient way. The network is designed to bridge this translational gap by creating a multidisciplinary training and research network that will give ESRs the ability to transfer their knowledge from basic sciences to industrial applications. FoodTraNet will cover techniques including stable isotopes, target, suspect, non-target screening and mass spectrometry imaging to obtain the following objectives: 1) identify biomarkers and bioactive compounds to assure food quality and traceability; 2) characterize novel foods to support food safety and security; and 3) developed and characterize new products based on the latest advances in nanotechnology: edible photonic barcodes; nano-sensors; multi-functional polymer nanostructured materials; and new, active and intelligent packaging. These goals will be achieved by a unique combination of "hands-on" research training, non-academic placements/courses and workshops on scientific and complementary transferrable skills facilitated by the academicnon- academic composition of the consortium. Strong industry involvement in the project, with full participation of CONCAST and SMEs from different sectors, will provide ESRs with the transferable skills necessary for thriving careers in a burgeoning area that underpins food sustainability through innovative technological development across a range of diverse disciplines.

Researcher(s): Promoter: Covaci Adrian, Co-promoters: van Nuijs Alexander; Giulia Poma​

Research team(s): Toxicological Centre

Project website: https://www.foodtranet.org/

Abstract

The human exposome covers the totality of non-genetic exposures from conception throughout the life course. The Flemish exposome project, FLEXiGUT, combines the unique and complementary expertise in Flanders on dietary- and environment-related human biomarkers and biomonitoring, metabolomics, microbiome research and epidemiology to investigate the complex human exposome. This first large-scale Flemish Exposome study, will make use of biomonitoring and -omics based technologies on the available biological matrices of the Flemish Environage Birth and the Flemish Gut Microbiome cohorts. Associations between the acquired exposome metadata and chronic low-grade gut inflammation parameters and related diseases will be analysed using an integrated -omics approach. Our pioneering results will be validated through extension towards other international cohorts.

Researcher(s): Promotor: Covaci Adrian

Research team(s): Toxicological Centre

Abstract

Autophagy is a ubiquitous process that removes unnecessary or dysfunctional cellular components from the cytoplasm. Defective autophagy is currently emerging as a hallmark of many diseases. In this framework, there is strong interest in pharmacological agents that stimulate autophagy (so-called 'autophagy inducers'), as a potential treatment for these diseases. The unequivocal validation of autophagy induction as a therapeutic strategy, however, is far from established. Many obstacles persist, including the lack of druglike, selective autophagy inducers and readily translatable preclinical results that are obtained with such compounds. In addition, the availability of reliable biomarkers for autophagy and additional fundamental safety data for the approach, would strongly contribute to its validation. This proposal addresses existing limitations in the state-of-the art in the domain. We have recently carried out a phenotypic High-Throughput Screen (HTS) on a curated compound library. Members in this library were preselected from different providers based on in silico druglikeness scores. One compound family that was identified in the screen and maximally validated prior to this application, will be further optimized chemically for autophagy induction potency and biopharmaceutical properties. The biopharmaceutical profile of the best new representative will be thoroughly characterized in vivo, both involving PET-based pharmacokinetics and phenotypic pharmacodynamics. The compound will subsequently be investigated in two mouse models of diseases characterized by defective autophagy: atherosclerosis and Charcot-Marie-Tooth periferal neuropathy. In addition, we propose to investigate whether autophagy induction is intrinsically sufficiently safe as a therapeutic strategy. Existing hypotheses that autophagy induction could accelerate tumorigenesis and/or tumor growth will be investigated in vivo. In the same framework, metabolomics will be relied on to monitor eventual cellular stress fingerprints that result from chronic or long-term autophagy stimulation. Finally, metabolomics will also be relied on to identify cellular biomarkers of autophagy induction. The latter will be validated in plasma samples of animals that were systemically treated with autophagy inducers. Combined, we expect the knowledge and tools that are generated by this proposal to have strong impact on the field of autophagy research and ongoing endeavors to validate autophagy induction as a therapeutic strategy.

Researcher(s): Promotor: Van Der Veken Pieter Co-promotor: Martinet Wim Co-promotor: Stroobants Sigrid Co-promotor: Timmerman Vincent Co-promotor: van Nuijs Alexander

Research team(s): Medicinal Chemistry (UAMC)

Abstract

- Phthalates (i.e. DEHP) and alternative plasticizers (APs) are used in plastics to increase their elasticity and extend their lifetime. - Leaching of plasticizers from indwelling medical devices used in the neonatal intensive care unit (NICU) might expose neonates to these chemicals at levels far exceeding tolerable daily dose recommendations. - Although awareness of these plasticizers is growing, they are still used in many (most) medical devices even in the NICU. - Premature neonates are extremely vulnerable to external insults. - This project aims to explore the utility of levels of plasticizers and their metabolites in a keratinous non-invasive matrix (hair) and in urine as a diagnostic tool for cumulative and past exposure in the neonatal intensive care unit. - The possibility that this matrix can detect past and cumulative exposure in this vulnerable population is a novel approach and is expected to provide fresh insights into the detection of past exposure to these chemicals. - The studied plasticizers have toxic effects on neuronal and pulmonary cells, as proven in in vitro and in vivo (animal and human) models. - Based on these pathophysiological effects, we hypothesize that exposure to these plasticizers during the NICU stay contributes to the long-lasting impaired (neurocognitive and lung) development that is frequently observed in neonates after discharge from NICU.

Researcher(s): Promoter: Jorens Philippe, Co-promoter: Covaci Adrian, Mulder Antonius

Research team(s): Laboratory Experimental Medicine and Pediatrics (LEMP)

Abstract

Plastic particles are everywhere in the environment and there is concern about the adverse effects they may have on organisms, and subsequently on ecosystems. Much global attention has been directed towards so-called microplastics, i.e. plastic particles with dimensions in the millimeter to micrometer range. Microplastics slowly degrade in the environment, by physical and chemical processes, into smaller and smaller entities, eventually reaching the nano-size domain. Due to difficulties in sampling and characterisation, almost nothing is known about the amounts and behaviour of extremely small plastic particles with dimensions on the order of nanometers, i.e. nanoplastics. Our project addresses this knowledge gap. We will measure and model the chemical reactivity, biouptake, and bioaccumulation of nanoplastics and their adverse effects on aquatic organisms. The results will provide fundamental information which enable robust risk assessment strategies to be developed that inform environmental policies.

Researcher(s): Promotor: Blust Ronny; Co-promotor: Town Raewyn

Research team(s): Systemic Physiological and Ecotoxicological Research (SPHERE)

Abstract

The ENVIRONAGE (Environmental Influences on Early Ageing) birth cohort was initiated in February 2010 as a collaboration between Hasselt University and East-Limburg Hospital in Genk, Limburg, Belgium. This longitudinal study aims to investigate the influence of environmental exposures during pregnancy and early life on the health of children. Recruitment occurs at birth and the first follow-up occurs at the age of four to six years, and at the pre-adolescent age.

Researcher(s): Principal investigator: Tim Nawrot

Research team(s): Centre for Environmental Sciences (CMK, University of Hasselt)