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Research project (§ 26 & § 27)
Duration : 2019-11-01 - 2023-10-31

Wider research context: Our group is interested in understanding how fungal transcription factors function in the context of chromatin. This structure is particularly relevant for synchronized expression of physically linked gene clusters. We have studied the Aspergillus nitrate cluster (primary metabolism, PM) and also work on chromatin-level regulation of fungal secondary metabolite gene clusters (SMGCs). It is now well established in many fungi that SMGCs are silenced by heterochromatin formation and activated by wide-domain and pathway-specific regulators. The interplay between those processes is largely unknown. Hypotheses, research questions and objectives: The activation process must counteract heterochromatic silencing and we know that this requires factors such as Velvet/LaeA or histone demethylases (KdmB) but how the process works mechanistically, is poorly understood. We would like to add mechanistic information on the silencing and activation process of SMGCs and want to understand how co-regulation of these “toxin-islands” is insulated from surrounding genomic regions. Experimental approaches and methods: we will use Aspergillus nidulans as model and first plan to map the positions of the main silencing regulator HepA and the activators LaeA and KdmB by ChIP-seq. We then will apply Cas-ID, a locus-specific chromatin pull-down technique based on sgRNA-guided enzymatically disabled dCas9 fused to a biotinylating domain, to study the local proteome composition at the regulator target sites in silent and active SMGCs. We will compare these proteomes to genomic regions immediately outside with the aim to identify and then characterize factors that are specific for the chromatin of co-regulated SMGCs. Originality and innovation: Cas-ID has not yet been applied in fungi and we expect that this new technique will provide completely novel insights on chromatin composition, associated factors and their post-translational modifications (PTMs) in and around SMGCs. We expect to identify new chromatin-related SMGC regulators for repression and activation and get some novel information how they functionally or physically interact. All this together will provide a more detailed mechanistic view on chromatin-level regulation of SMGCs and their insulation from the surrounding genomic regions and will also provide possibilities for epigenetic engineering to activate orphan SMGCs and find novel metabolites. Involved scientists: Joseph Strauss´ lab has pioneered studies in chromatin-level regulation of fungal gene clusters in primary and secondary metabolism. They are publishing regularly on this topic since many years as leading lab or in collaboration with other groups in high-ranking journals. There is a long-standing and successful cooperation with the proteomics group of Friedrich Altmann who will be involved mainly in the Cas-ID part of the project and characterization of protein PTMs.
Research project (§ 26 & § 27)
Duration : 2019-05-01 - 2020-10-31

Targets of project In Phase I of project a biosensor for androgens on the basis of Aspergillus nidulans should be established and validated –using the reaction of the test system with different androgen concentrations. In Phase II of project different samples from animals at different reproduction stages will be analyzed. The microbiom of the animals will be considered and compared to samples only stored at frozen stages.
Research project (§ 26 & § 27)
Duration : 2019-06-01 - 2023-05-31

The plant-specific family of arabinogalactan proteins (AGPs) is implicated with a multitude of biological functions and their O-glycan might be crucial for either ligand interactions or for crude biophysical or structural protein properties. In this research proposal, however, I propose a role of O-glycosylation of the AGP type for protein fate by introducing the concept of an O-glycosylation checkpoint. I discuss evidence for the importance of O-glycosylation for protein fate in all eukaryotes and specifically describe the case of the moderately O-glycosylated FASCICLIN-LIKE ARABINOGALACTAN PROTEIN 4 (FLA4) from Arabidopsis thaliana. FLA4 abundance and localization strongly depends on its O-glycosylation. With a set of hydroxyproline-specific galactosyl transferases FLA4 acts in a linear genetic pathway necessary for normal root growth, salt tolerance and seed coat structure. Using FLA4 as genetic paradigm for a functional O-glycoprotein, I suggest hypothetical models of where and how O-glycosylation might influence the fate of plant proteins. I propose experimental approaches to elucidate the genetic and molecular mechanisms that determine the fate of FLA4 in dependence of its O-glycosylation status. Precise definition of proline hydroxylation and -glycosylation as well as molecular identification of crucial modification sites on FLA4, the cell biological elucidation of the involved organelles and the investigation of the degradation mechanism will comprise the first example for an endogenous plant protein that is controlled by its O-glycosylation state. Forward genetic isolation and next generation sequencing-based identification of suppressors of O-glycan dependent control of FLA4 abundance will provide novel genetic components of this process. A remarkable set of signalling proteins that have not previously been considered to be O-glycosylated, potentially also contain this modification. Therefore, it is likely that the O-glycan checkpoint acts on various regulatory pathways. The outcomes of this project will provide an important contribution to our fundamental knowledge of protein glycosylation and proteostasis and might thus contribute to improved stress tolerance of crop plants and the use of plants as factories

Supervised Theses and Dissertations