Title Promoter Affiliations Abstract "Molecular mechanisms of zinc tolerance in Suillus luteus." "Jan COLPAERT" "Environmental Biology" "Zinc is an essential micronutrient for all organisms but can become toxic when present in elevated concentrations. The quantity of free zinc in the cell has to be controlled precisely to assure growth and reproduction in all circumstances, in spite of the potential toxic nature of this element. Eukaryotes evolved a zinc homeostasis network restricting the zinc influx, storing it in specific organelles and/or chelating it when present in elevated concentrations [1]. However, at prolonged exposure or in case of extremely elevated concentrations in the environment, these basic detoxification mechanisms are not longer sufficient for most organisms and tolerant ecotypes can evolve due to selective pressure. The ectomycorrhizal fungus, Suillus luteus, evolved ecotypes with an adaptive tolerance for zinc, cadmium and/or copper. These ecotypes can protect their host from toxicity and are of crucial importance for the preservation of vegetation on contaminated sites [2,3,4]. Own research pointed out that adaptive zinc tolerance in Suilloid fungi relies on active transport of zinc out of the cell [5,6]. Transcriptome analysis yielded a lot of TDFs (transcript derived fragments) of which a few could be linked to zinc detoxification but of which none could be linked directly to the transport of zinc or zinc complexes [7]. Therefore the players of the zinc homeostasis network, responsible for adaptive tolerance in Suilloid fungi, are still unknown. Objectives of the project The overall objective of the current project is to unravel the molecular biological mechanism responsible for adaptive zinc tolerance in Suilloid fungi. To realize this overall objective, three sub objectives are set: 1. Identify and characterize some components of the zinc homeostasis network of Suillus luteus. There will be focused on cation transporters with a function in zinc fluxes. 2. Gain an understanding of the regulation of the zinc homeostasis network. Upstream components will be identified and will shed light on the zinc sensing mechanism of the eukaryotic fungus cell. 3. Determine the interaction of other metals and the zinc homeostasis network." "Zinc protoporphyrin IX formation in relation to the colouring of nitrite-free dry fermented sausages." "Ilse Fraeye, Chris Michiels" "Bioengineering Technology, Ghent and Aalst Technology Campuses, Centre for Food and Microbial Technology" "The colour of fresh meat is mainly determined by myoglobin, which is found in large quantities in mammalian muscles (≈ 30% of the total muscle proteins). Myoglobin has a globular structure and consists of one chain of 153 amino acids enclosing a non-protein heme group. This heme group, an iron-containing protoporphyrin IX, is the active center of myoglobin and directly responsible for the colour of meat.Traditionally, sodium nitrite and/ or potassium nitrate are used for the colouring of meat products. Nitric oxide (NO), formed after the reduction of the added nitrite and/ or nitrate, is bound to heme. This resulting nitrosyl myoglobin gives raw meat products their characteristic red colour.Consumers are increasingly aware of the impact and the importance of a healthy lifestyle and therefore have a growing interest in healthy food. Because of this increasing awareness, the use of ""chemical"" additives is becoming less obvious. Especially sodium nitrite (E250) and potassium nitrate (E252) are controversial. Although nitrite also increases the microbial shelf-life and safety, this additive is nevertheless considered to be undesirable as it is involved in the formation of carcinogenic N-nitrosamines. Therefore, strict regulations were formulated to limit the use of nitrite and nitrate. Under current European legislation, the maximum allowed amount of sodium nitrite for all meat products is only 150 mg / kg [Directive 2006/52 / EC].For a long time nitrosyl myoglobin was regarded as the only molecule that could give meat products their attractive red colour. In contrast to this generally accepted idea, however, it was established in 2004 that the red colour of Parma ham, a traditional Italian dried ham, was not due to the formation of nitrosyl myoglobin but zinc protoporphyrin IX was identified as the colour-forming pigment. Similar to heme, zinkprotopofyrine IX has a protoporphyrin IX structure, but instead of iron zinc is complexed in the pyrrole ring.Until now, the formation mechanism of zinc protoporphyrin IX has not yet been clarified sufficiently. More knowledge about this red pigment, however, would be interesting to replace sodium nitrite or potassium nitrate in other meat products with regard to the colour formation, such as, for example, in dry fermented sausages. The purpose of this doctoral study is to assess whether zinc protoporphyrin IX can be formed during the production of nitrite-free dry fermented sausage and what effect it has on colour formation. Additionally, investigation will be done on the influence of product and process factors on formation of this natural pigment, in order to obtain an attractive colour in meat products without any addition of additives." "A profound study of the mechanism and field of application of the increase of Glucocorticoid Receptor transcriptional activity by zinc. " "Claude Libert" "Department of Biomedical molecular biology" "We aim to find a treatment for systemic inflammatory response syndrom (SIRS), which is an often fatal acute condition occuring after serious trauma, bleeding, burning and infection (sepsis). Despite SIRS is an inflammatory condition, anti-inflammatory glucocorticoids (GCs) have no therapeutic benefit in SIRS. GCs bind to the GC receptor GR. Our work in mouse SIRS models show that GCs might have therapeutic future in SIRS if we find a way to stimulate the GR dimer rather than the GR monomer pathway. A GR dimer functions as a true transcription factor, binding GRE DNA elements and inducing gene transcription. In SIRS, this dimer pathway is inactivated. We found that zinc (Zn) protects in a mouse model of SIRS and that the effect of zinc needs GR dimerization. Here, we want to find the mechanism by which Zn helps GCs in stimulating the GR dimer pathway. Our data suggest a direct effect of Zn on the GR dimerization process, which will be further studied in work package 1 (WP1) and at several levels of the GR dimer pathway (dimerization, DNA binding, co-factor recruitment, GRE-gene induction). In WP2, we will study the involvement of the primary Znrecognizing Metal Transcription Factor-1 (MTF-1) in these processes using MTF-1-KO cells and mice and in WP3, we will study the impact of Zn on the gut, the primary target in SIRS, by studying gene expression in relation to GCs and the microbiome. WP4 addresses therapeutic options for Zn to help GCs in GC resistant SIRS and sepsis. " "Study of Process Technology and Device Architecture for Amorphous Indium Gallium Zinc Oxide Thin Film Transistors" "Paul Heremans" "ESAT - MICAS, Microelectronics and Sensors" "Amorphous oxide semiconductors (AOS) based thin film transistors (TFTs) find potential applications in the field of large area electronics. Among the various AOS, amorphous Indium Gallium Zinc Oxide (a-IGZO) based TFTs have been broadly researched in the display industry. The characteristics such as high mobility, large-area uniformity, transparency, and low-temperature processing make a-IGZO TFTs suitable for next generation Active Matrix  Liquid Crystal Displays (AMLCDs) and Active Matrix Organic Light Emitting Diode (AMOLED) displays. The advancement of a-IGZO TFT based applications relies on a thorough understanding of the impact of the material properties and process integration on the performance and reliability of a TFT. The objective of this thesis is to fabricate a-IGZO TFTs with different architectures and to understand the impact of different materials and process integration variables on device performance." "Influence of Lactobacillus fermentation on the iron and zinc bio-accessibility in vegetable products" "In vegetable products (legumes, grains and vegetables), the iron and zinc bio-accessibiltity is low. This is partly due to the presence of phytates, polyphenols and fibres, making complexes with iron en zinc. In this way the bio-accesibility and bio-availablity of these minor components is inhibited. In this project proposal, it is aimed to increase the bio-accessibility by using fermentations with Lactobacillus strains." "Understanding the anti-diarrhea effects of zinc at the Paneth cell level." "Claude Libert" "Department of Biomedical molecular biology" "Diarrhea in humans and animals causes immense socio-economic problems. The food and feed additive zinc (Zn) has clear protective effects against diarrhea. In pigs, post weaning diarrhea (PWD), usually resulting from Enterotoxigenic E. coli (ETEC), is efficiently treated by Zn. However the use of Zn will be forbidden from 2022 on, because of environmental issues. To replace Zn efficiently as a treatment, we have to understand its function. The host lab has unraveled a new mechanism, based on a TNF model in mice. The focus lies on Paneth cells, which form the epithelial layer in the crypts in the small intestine. These cells undergo cell death by TNF, leading to permeability and inflow of bacteria in the spleen and other organs, causing septic death. The details of the impact of TNF and Zn on these cells depend on their gene expression status, which is influenced by the microbes in the gut. To understand these details, we must isolate Paneth cells via FACS, study their genome wide gene expression by RNAseq, and culture these cells to study in vitro effects of TNF and Zn. Optimizing these assays is a major challenge. Furthermore, I will establish a mouse model of PWD using ETEC bacteria and study the role of PC cell death, permeability, TNF, the heat-labile toxin of ETEC and Zn using my newly established assays. With this project, I hope to open new possibilities for the treatment of diarrhea, including PWD, an economically huge issue in an area as Flanders." "Iron and zinc absorption in food products derived from processed wheat" "Jan Delcour" "Translational Research in GastroIntestinal Disorders, Food and Microbial Technology (CLMT)" "Iron (Fe) and zinc (Zn) deficiencies are widespread in developing countries and in some industrialised countries. This can lead to the so-called hidden hunger in which people do not get the essential vitamins and minerals they need for their growth and development. Cereal crops are an important source of minerals. However, only 3-5% of Fe and Zn in wheat is bio-accessible as both these minerals are (i) physically entrapped and (ii) occur as chelates in aleurone cells of the bran layer. The physical barrier is set by the rigid cell walls which withstand conventional milling and action by human digestion enzymes. In addition, mostly phytate, the main storage form of phosphorus, chelates them. There is a need to increase the content of bio-accessible minerals in cereals to make diets more balanced and healthy. It has been shown that steeping, sprouting and hydrothermal processing of wheat results in an increased in vitro bio-accessibility of Fe and Zn as a result of phytate hydrolysis in combination with mechanical cell wall opening (e.g. by milling) in whole grain-based products. The current project aims to evaluate whether consumption of foods based on such processed wheat increases mineral absorption in healthy humans." "Generation, characterization and use of immortalized Paneth cells, to elucidate and mimic the therapeutic mechanism of Zinc against infections." "Claude Libert" "Department of Biomedical molecular biology" "Zinc (Zn) is a mineral, taken up from the food. Zn deficiency is related to intestinal infections and sepsis. Zn addition has been found to have therapeutic effects in animals and humans. However, the mechanism is not known. It is thought that Zn modulates the composition of the gut microbiome, by modulating gene expression in the intestinal epithelial cells (IECs). Our work hypothesis is that Zn stimulates antimicrobial pathways in the most specialized cells of the IECs, the Paneth cells (PCs). PCs store Zn and respond to it, but the lack of sufficient amounts of PCs has hampered their detailed study so far. We have decided that the generation of an immortalized PC line (iPCL) would be a tremendous step forward, to study the effects of Zn, but also to develop an assay system, to screen for molecules which have a Zn-like effect, and could help to reduce the necessary dose of Zn that should be provided to patients and animals. This is important because Zn is a heavy metal and should not cause environmental contamination. With my project, I will make ample use of our PC-specific cre-mice and use them to purify PCs and immortalize them. Once the iPCL is there, I will study the impact of Zn on transcriptomics and proteomics. Third, I will develop a screening assay, and screen a custom compound library and a larger discovery library. Finally, I will evaluate the possibility to identify in mouse feces, a PC biomarker that might reflect the amount and/or secretion status of PCs." "Zinc homeostasis in ectomycorrhizal symbiosis: nutrition and beyond" "Joske Ruytinx" "Department of Bio-engineering Sciences, Plant Genetics" "Mutualistic associations between tree roots and fungi, ectomycorrhizas (ECMs), are ubiquitous. Through these associations, trees can colonize, establish and survive in a wide range of soils. Underground hyphal networks regulate nutrient access and limit translocation of pollutants in exchange for plant derived sugars. Traditionally, transport of macronutrients throughout the fungal mycelium and towards the plant is well studied. However, regulation of nutrient exchange and its impact on sustainability of the mutualism remains unclear. Indeed, including micronutrients in the current models of symbiotic transport is urgently needed to fully understand establishment and resilience of ECM mutualism. The aim of the current project is to unravel the role of micronutrient Zn in ECM fungi and symbiosis. We will study Zn dynamics and trafficking upon environmental change to evaluate the contribution of ECM fungi at plant Zn balances and to explore the potential of Zn to act as a molecular signal beyond its trophic role. Zn transporters of the CDF and ZIP family will be characterized, and in-depth analysis of a putative Zn responsive transcription factor will be performed. The results of this study will contribute profound knowledge on Zn homeostasis and gene regulation in ECM, linking cytoplasmic Zn availability to adaptive growth responses. This will ultimately lead to a better understanding of the pervasive power of ECM fungi in terrestrial ecosystems" "Synthesis of fused isothiazole derivatives as inhibitors of cyclin G associated kinase (GAK) and phosphoinositide kinase FYVE-type zinc finger (PIKfyve)" "Wim Dehaen" "Sustainable Chemistry for Metals and Molecules" "Previous research in our lab led to the discovery of 6-aryl-isothiazolo[4,3-b]pyridines as potent and selective inhibitors of either cyclin G associated kinase (GAK) or phosphoinositide kinase FYVE-type zinc finger (PIKfyve). Both kinases are promising drug targets for the development of broadspectrum antiviral agents. Using the current chemistry, 3,6-disubstituted isothiazolo[4,3-b]pyridines can easily be prepared. In this project proposal, we will focus on the establishment of synthetic procedures to have access to novel fused isothiazolo derivatives, which will allow us to broaden chemical space that can be studied as GAK and PIKfyve inhibitors. The design will be guided by molecular modeling and biochemical kinase assays. Promising compounds will be investigated for activity against various viruses, such as the dengue virus and the venezuelan equine encephalitis virus."