WHAT WE DO

We study genes that are important for cognitive function and investigate how can single genetic defects result in dramatic and severe neurodevelopmental disorders, such as intellectual disability (ID) or autism (autism spectrum disorder, ASD).

HOW WE DO IT

We introduce equivalent mutations that are found in individuals with ID or ASD into the genes of a fruit fly, Drosophila. We use various approaches, depending on the type of mutation, such as RNA interference (to mimic loss-of-function), overexpression (to mimic gain-of-function), or CRISPR/Cas9-based genome editing (to model missense and patient-specific variants).

The fruit fly genetic models are inspected for cognitive phenotypes. We mostly focus on habituation, a conserved form of learning that we found to be relevant for ID and ASD. During habituation, a reaction to repeated irrelevant stimuli gradually wanes. They are filtered out and our brain can focus on important matters. A typical example is learning to ignore the sound of a ticking clock. Habituation protects our brain from information overload and it is required for higher cognitive functions, such as memory. It can be assessed in both ID/ASD individuals and their Drosophila models, which makes it suitable for the investigation of disease mechanisms and treatment targets.

You can read more about genetics, molecular control and clinical relevance of habituation learning in our review.

Just as the human brain gets used = habituates to clock ticking, fruit flies can suppress their jump response to a repetition of a light-off stimulus. In the beginning, they perceive it as a danger and respond with a jump. After few repetitions, they learn that it does not cause any harm and stop jumping. Flies with habituation deficit are not able to suppress the response and continue jumping, like in the video below. Our habituation assay is thus called light-off jump habituation. With this assay, we can test 24 flies in less than 30 minutes.