Drosophila Models of Brain Disorders

Our research focuses on dissecting molecular networks and mechanisms underlying human brain function and disease.

Mutations in more than 400 genes are known to give rise to Intellectual Disability (ID), providing an exciting starting point to study this problem. Accumulating evidence suggests that some of these genes ("ID genes") operate together to control specific aspects of nervous system development and function. However, the function of most ID genes is unknown or poorly characterised at present. We aim at providing functional data for all ID genes and at systematically identifying their molecular connections.

In order to be able to investigate the large number of genes, we use a powerful genetic model organism, the fruitfly Drosophila melanogaster. In flies, genes can be manipulated specifically in neurons with relative ease, and consequences for neuronal architecture, function and cognitive behaviour of the fly, such as learning and memory, can be studied and compared. Furthermore, we use the gained knowledge on ID gene function and the fruitfly as a model to search for genetic and chemical modifiers of fly "ID" phenotypes. This research identifies novel candidate genes and potential medication for humans.

Recent data including our own indicate that some forms of ID indeed result from reversible inabilities of the nervous system, raising serious hope that impaired cognition can be treated. Beyond the expected fundamental insights into molecular pathways that wire the brain, our research also aims at significantly contributing to such developments.

Whereas these projects primarily aim to understand the neuronal basis and molecular underpinnings of their specific human disorders, they also serve as pilot projects for our systematic approaches to ID, as they continuously improve our knowledge on ID-relevant fly phenotypes. We also become increasingly interested in Autism, Attention deficit hyperactivity (ADHD), Schizophrenia and language disorders, and into the arising theme that the genetics and neurobiology of these disorders significantly overlap with each other and with Intellectual disabilities.