Alternative splicing in Drosophila Development
Our main research interest focuses on the regulation and function of alternative splicing. Recently it has become evident that regulation at the level of gene transcription presents only one part of the regulation network of gene expression, being important for the development and life of organisms. Over 95% of human genes are targeted by alternative pre-mRNA splicing, and an increasing number of diseases are being associated with the misregulation of this process. Surprisingly, very little is known as to what extent alternative splicing intersects functionally with other biological pathways. We use Drosophila as a model system to address different aspects in the field of alternative splicing. Currently, we have two main projects in the lab:
I. Sex-specific alternative splicing in Drosophila
Drosophila sex-determination is a prime example of an alternative splicing (AS) cascade where Sex lethal (Sxl) as a master regulator controls alternative splicing of the key sex-determination genes Sxl, transformer (tra), male-specific-lethal 2 (mls-2), doublesex (dsx), and fruitless (fru). Previous genome-wide studies revealed extensive sex-specific splicing in adult flies (Hartmann et. al. 2011). These changes were partially tissue-restricted and suggested that additional regulatory mechanisms exist in parallel to the SXL/TRA pathway to control tissue-restricted sex-specific splicing. Interestingly, signals from the germline appeared to be important for the regulation of some sex-specific splicing events in the head. We performed transcriptomic analysis by RNA-Seq to identify sex-specific differences in alternative splicing in the larval and adult nervous system of Drosophila. We are analyzing the mechanisms by which sex - or germline-specific AS events are regulate and characterize the function of these isoforms in vivo.
II. Investigating the role of RNA-binding proteins in Drosophila neural development
The impact of AS on neural development is highlighted by reports of isoforms linked to specific functions in neural development, but still very little is known about the regulation of these alternative splicing processes. The aim of this project is to identify splicing factors and RNA binding proteins involved in Drosophila neural development using an in vivo RNAi screen. Our candidate list comprises about 400 Drosophila splicing factors and RNA binding proteins which will be knocked down specifically in the mushroom bodies. The mushroom bodies are important brain centers of Drosophila fulfilling both elementary functions such as visual context generalization and higher-order functions such as courtship behavior, decision making, and olfactory learning and memory. Many tools to target this tissue have been developed lately. Their complex lobular neuropil organization makes the mushroom bodies an interesting model to investigate the effects of knockdown of RNA binding proteins on neural development.
We are looking for motivated students who would like to join our small group for their Bachelor or Master thesis (biology and/or molecular medicine).