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Research project (§ 26 & § 27)
Duration : 2024-01-01 - 2027-12-31

Wider research context Of the five human heme peroxidases, evolved to perform widely divergent functions, thyroid peroxidase (TPO) is the least well studied. The multidomain membrane protein catalyses the biosynthesis of thyroid hormones, which are essential for metabolism, growth and development of the human body. With the use of hydrogen peroxide TPO catalyses the iodination and coupling of tyrosine residues on the surface of thyroglobulin (TG) in the thyroid gland. However, there are open questions about substrate selectivity, biochemical characteristics, the coupling mechanism and the roles of the individual domains. Critically, TPO is at the core of two autoimmune thyroid diseases that combined afflict nearly 150 million people but the only two clinically approved TPO inhibitors are not specific. Objectives This project will elucidate the biochemical and structural characteristics of TPO. The main goals are (I) understanding the kinetics and substrate specificity of TPO, (II) provide structural data of TPO alone and of relevant ligated states and (III) clarify the mode of action of TPO inhibitors. Approach In preliminary work an expression and purification protocol for truncated TPO variants was established. Importantly, it was found that it is possible to reconstitute and link the heme cofactor even after purification, yielding highly pure and enzymatically active recombinant TPO. This allows the first detailed spectroscopic, thermodynamic and structural study of the enzyme. This will include an analysis of the reaction kinetics of TPO using a range of methods, including stopped-flow UV-vis spectroscopy for pre-steady kinetics, analysis of the interaction with small molecules (i.e. inhibitors, ligands) and TG with thermodynamic and mass spectroscopic assays. Finally, this project aims to solve the X-ray crystal structure of TPO alone and in complex with biologically relevant substrates, ligands and inhibitors. Level of originality TPO is crucial in thyroid hormone biosynthesis. However, to date the available biochemical and structural data is scarce and does not allow (I) a clear rationalization of the structure-function relationship of the active site architecture and TPO reactivity, (II) the role of the additional TPO domains and (III) the design of new more specific inhibitors. This project aims to provide a complete enzymatic and structural characterization of TPO to address these issues. Primary researchers involved Vera Pfanzagl graduated from the international PhD program BioToP at BOKU in 2019. She worked primarily on structure-function relationships of heme enzymes and during her postdoc focused on human heme peroxidases. Within this Fellowship she aims to obtain her habilitation to advance her academic career. She will be supported and coached by Kristina Djinovic-Carugo, a highly recognized expert in structural biology and head of EMBLE Grenoble and Chris Oostenbrink (professor at BOKU), an expert in molecular modelling and simulation.
Research project (§ 26 & § 27)
Duration : 2023-12-01 - 2028-11-30

Through photosynthesis, marine algae convert gigatonnes of carbon dioxide into carbohydrates every year. In the form of algal polysaccharides, these structurally complex biomolecules determine to a large extent how much carbon is stored in the oceans. Specialised marine bacteria unlock this carbon energy by breaking down the polysaccharides through the action of carbohydrate-active enzymes (CAZymes) and releasing the carbon dioxide back into the atmosphere. However, some of the polysaccharides are not recycled quickly, but sink into the deep sea and sediments, where they can store carbon for millennia. To better understand these processes, great efforts are needed to further explore the marine carbon cycle. The same advances are also important to support emerging efforts to use algal biomass as a new sustainable resource for the bioeconomy. The enzymatic machinery responsible for the degradation of polysaccharides by marine bacteria has remained largely unexplored because of the size and heterogeneity of algal polysaccharides. Pure and defined oligosaccharides needed for systematic screenings of marine CAZymes are currently not available. Since conventional chemical synthesis is time-consuming and often not general enough, ASAP aims to obtain collections of oligosaccharides related to different classes of algal polysaccharides by using automated glycan assembly (AGA) technology. Oligosaccharides with many different sequences and sulfation patterns will be prepared from small sets of monosaccharide building blocks. Incubation of the synthetic oligosaccharides with samples containing carbohydrate-degrading activity and subsequent HPLC-MS analysis of the degradation products will provide information on: 1) the collective enzyme activities of a bacterial community in seawater and sediment samples; 2) the abilities of individual bacterial strains to degrade specific polysaccharides; 3) the substrate specificities of purified CAZymes.
Research project (§ 26 & § 27)
Duration : 2022-06-01 - 2025-05-31

The final sensorial quality of a wine is the result of a multitude of interactions between all the chemical components within the wine and specific environmental factors such as the temperature of the wine. Since influenced by numerous factors such as grape varieties, growing conditions, climate change, yeast strains, wine making technologies, human experiences, the evaluation and preservation of wine quality – in terms of reproducibility from year to year - is nowadays the main challenge for both wine producers and wine science community. Viticultural practices aim primarily at producing high quality grapes that would reflect varietal flavours and aromas and/or characters typical for a specific region or terroir. In Austria, Districtus Austriae Controllatus (DAC) is a classification for regionally typical quality wine that provides products of distinction in wine market. An accurate evaluation and assessment of the wine quality, identity and typicity is of high significance for vintners to perform proper wine classification and target marketing. The aim of this project is on grape and wine quality evaluation, and regional typical quality characterization and prediction using elemental and sensory analysis, non-targeted and targeted metabolomics, spectroscopic approaches, and artificial intelligence. Grape quality is the most important factor for making high quality wine and some grape metabolites can have a strong relation to the wine quality. The relationship between the grape metabolites and the wine quality will be explored using non-targeted metabolomics and spectroscopic approaches and wine quality prediction models generated by artificial intelligence and machine learning algorithms. Of particular focus in this project is providing detailed chemical characterization that elucidates the influence of the Viennese wine growing region (origin) on Viennese Gemischter Satz DAC and Grüner Veltliner. As final output of the project, software, apps and a unique quality mark tag will be developed, for wine quality prediction and authenticity assessment based on established databases. This solution will be designed and developed to prove the identity and authenticity of each bottle and trace them. In turn, the outcomes of this project aim to both support origin marketing and future maintenance of wine production processes and wine quality in Vienna.

Supervised Theses and Dissertations