Some fungal species splice their mRNA during gene expression in an alternative (differential) manner. But how wide-spread is this cellular process in the fungal kingdom and which processes of the microbial lifestyle are affected? Does alternative splicing facilitate multicellularity? One could also imagine that the switch from peaceful mutualism to pathogenic behavior may involve regulated alternative splicing.
To address these issues, we analyse RNA-Seq data of various fungi, such as Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans. Various analysis tools are tested in order to identify (unknown) alternative splicing events. Detected alternatively spliced genes are viewed in a cell biological context. We study conservation of these genes and investigate phylogenetic distribution.

The focus of the project lies on age-related protein damage that leads to aggregates. These cannot be degraded anymore and therefore accumulate until the cell suffers from major functional inhibitions and finally triggers apoptosis. The goal is to determine what are the most or also least favoured targets in terms of aggregation. Also information from structure and prominent aggregates will be included. Furthermore connections and functions will be examined by computational modeling and the use of transcriptome data.

Bacteria keep their DNA twisted and writhed in a state of a supercoil. The level of this DNA supercoiling is tightly regulated and influences gene expression genome-wide on the level of promoter activity and RNA chain elongation rate. It even promotes the formation of alternative DNA structures like Z-DNA, cruciforms and G-quadruplexes. The major regulatory role of supercoiling makes it an interesting target. If one can predict the response of a promoter to changes in the supercoiling level, one could conclude on regulatory programs that might become active when a certain supercoiling level is achieved by environmental perturbations. However, while we know that the global supercoiling level is in homeostasis in constant conditions, we know very little about local supercoiling levels, which is further complicated by the formation of topological domains with varying borders and a lack of experimental access to key properties of supercoiling. We shed light on these complex interactions by studying the effect of transcription dynamics on the supercoiling level in a local domain using omics data and computational models of the underlying processes in the model bacterium Eschierichia coli.