1. Glutamate receptors and synaptic physiology

In our lab we are interested in understanding the main control switch of the nervous system - the synapse.

With its powerful genetic toolkit, the fruit-fly Drosophila is an ideal model system for investigating synaptic biology and for identifying novel regulators of synaptic physiology that are also relevant to humans; at the primary amino acid level, Drosophila synaptic proteins share >70% similarity with their mammalian counterparts.

The neuromuscular junction (NMJ) innervating body wall muscles of developing Drosophila larvae is a complex synapse composed of muscle, neuronal and glial cells that shares many functional similarities with mammalian synapses, including mechanisms governing synaptic transmission and molecular processes underlying presynaptic vesicle release and postsynaptic receptor function. Because of their large size and accessibility, these excitatory, glutamatergic synapses are amenable to a range of electrophysiological, genetic, molecular and imaging analyses (all of which we use).

In our most recent work, we identified new factors governing synapse formation, neuronal morphology and muscle function in flies and mammalian cells and continue to search for novel regulators of synaptic function under both normal and pathological conditions.

Figure 1: A 3D image of the Drosophila larval neuromuscular junction. Motoneurons are shown in red, (postsynaptic) glutamate receptors in green. Muscle fibres innervated by the NMJ are not shown.

2. Ageing and ageing-associated diseases

Increasing longevity and improving physical and cognitive performance in old age is one of the main goals of biological ageing research. D. melanogaster is one of the most important model organisms for studying ageing, critical for identifying genetic, pharmacological and nutritional interventions that can extend lifespan in complex organisms. Many of these interventions, such as reduced insulin signalling or dietary restriction, can also alleviate pathological changes in various animal disease models, indicating common mechanisms underlying “normal” and pathological ageing.

Recently, we discovered a novel cellular mechanism by which lowered IIS can maintain synaptic transmission in a neuronal circuit during ageing (Fig. 2), pointing to new avenues for therapeutic interventions into ageing-related neuronal disorders. In addition, we use behavioural, molecular and computational approaches to investigate recently identified plant-based compounds for their possible anti-ageing effects both in healthy flies and in various Drosophila models of human neurodegenerative diseases.

Figure 2: Age-related loss of gap junctions in the Drosophila escape-response circuit leads to reduced physiological output in old flies. Attenuation of insulin signalling stimulates Rab-mediated recycling of gap junctional components, preventing the circuit’s functional decline (Augustin et al., 2017).