Latest SCI publications
Research project (§ 26 & § 27)
Duration : 2019-02-01 - 2022-01-31
In all eukaryotic cells, N-glycosylation is an essential and very common modification of proteins entering the secretory pathway. N-glycosylation affects many properties of proteins including their conformation and interaction with other proteins. This highly conserved process is characterized by the transfer of a preassembled oligosaccharide from a lipid carrier to selected asparagine residues present in a conserved amino acid sequence motif within newly synthesized proteins. A single membrane-bound multiprotein complex - called the oligosaccharyltransferase (OST) complex -catalyses the transfer of the oligosaccharide to newly synthesized protein. In yeast and metazoans, the OST complex is well studied and consists of one catalytically active subunit and several different non-catalytic subunits with accessory function. By contrast, little is known about the composition of the plant OST complex and the functional roles of many subunits remain elusive. Importantly, we have recently shown that human glycoproteins are incompletely N-glycosylated in plants. A comparison of structural features and amino acid sequence motifs from already known plant and mammalian OST subunits indicate clear differences that may explain the observed variation in N-glycosylation efficiency. Hence, it is hypothesized that the composition of the OST complex and the molecular function of individual subunits differ substantially between plants and mammals. In this project, we will investigate the N-glycosylation defect of OST mutants using a glycoproteomics approach and identify the plant OST complex composition by affinity purification coupled to mass spectrometry-based identification of proteins. Newly identified OST subunits will be explored for their involvement in N-glycosylation of proteins using biochemical methods, advanced bioimaging and phenotypic characterization of mutant plant lines.
Research project (§ 26 & § 27)
Duration : 2019-01-01 - 2022-12-31
HISTOVAR: Role of the histone variant H2A.Z in phytopathogenic fusaria Fusaria are among the most important group of phytopathogenic fungi infecting various economically important host plants worldwide. Besides enormous crop losses caused by these fungal attacks, fusaria are able to produce a diverse spectrum of natural compounds, referred to as secondary metabolites. These compounds include mycotoxins that frequently contaminate food and feed, thereby posing a serious health threat to animals and humans when consumed. A crucial step towards the development of efficient and durable strategies against fungal infections and contaminations with mycotoxins is to understand the regulatory network that orchestrates pathogenesis and secondary metabolite biosynthesis. Gene expression in eukaryotes functions within the context of chromatin. This includes histone posttranslational modifications that do not alter the DNA sequence, but affect the read out thereof, i.e. inducing or silencing expression of the underlying genes. These histone marks emerge more and more as key factors in regulating fungal virulence and secondary metabolism. Our working hypothesis is that during fungal development and during infection of the plant, the chromatin structure is dynamic and driven by changes in the histone marks deposited on the genome. These changes allow the expression of virulence- and secondary metabolite-related genes hitherto silent as optionally embedded in repressive chromatin. Among known eukaryotic histone marks, although regularly found as decorating transcriptionally active genes, the role of the variant H2A.Z remains to date a riddle, with conflictual roles often described for the same organisms. The function of H2A.Z in fungi has, to date, received very little attention. HISTOVAR proposes to focus on the chromatin dynamics in the two prominent Fusarium spp., Fusarium fujikuroi and Fusarium graminearum, infecting rice and wheat, respectively, and to study the role of so far overlooked – but likely essential – mechanisms involving H2A.Z during secondary metabolism and pathogenesis. HISTOVAR is a collaborative project between an Austrian and a French research group who both aim at, ultimately, finding the Fusarium’s “Achilles’ heel” that could serve as preferential target(s) for efficient, durable, and environment-friendly fighting strategies against fungal infections and mycotoxin contamination. By a combination of reverse genetics and whole genome approaches (transcriptome, metabolome and epigenome analyses), HISTOVAR will provide groundbreaking knowledge regarding the function of H2A.Z in fungal development, pathogenicity, and secondary metabolism.
Research project (§ 26 & § 27)
Duration : 2018-10-01 - 2019-09-30
Multiresistant microorgansims and tumors represent a continuous challenge to modern medicine. To encounter this situation, new pharmaceuticals have to be discovered and developed. A process that requires new, flexible strategies. Many pharmaceuticals originate from the kingdom of fungi. Bioinformatic analysis suggest that many more are still being hidden, even within exhaustively studied species. With this project, we want to activate these “silent” gene clusters with combination of the RNA-guided state-of-the-art tool CRISPR/CAS and an “artificial” activator, composed of viral and human transactivation domains. The system has already been established in other organisms and is therefore the tool of choice for our project. To our knowledge, there is no literature about the activation of “silent” gene clusters in filamentous fungi to this date. Should this project succeed, it would open completely new opportunities for the research of bioactive substances. Furthermor it would render the BOKU as an attractive partner for upcoming collaborations with pharmaceutical companies, who are interested in the discovery, development and production of new bioactive compounds, suitable for pharmaceutical industry.