new group leader at the ZML

Our research focusses on vesicular and non-vesicular membrane transport processes in neuronal and other excitable cells serving a fundamental role in cellular communication. Vesicular carriers transport and secrete biomolecules such as neurotransmitters, lipids, peptides and hormones by means of tethering and fusion and are essential entities for Ca2+-evoked exocytosis. In addition to vesicle-based routes, cells communicate through non-vesicular pathways at membrane contact sites formed at interorganelle interfaces. Emerging evidence suggests a profound impact of membrane contact sites in lipid and ion homeostasis, membrane biogenesis and in modulation of Ca2+-evoked release. Accordingly, membrane contact site dysfunction is associated with neurodegenerative diseases and metabolic disorders among others. However, the distinct contribution of vesicular and non-vesicular transport to neuronal function and how exactly membrane transport is spatiotemporally regulated in healthy and diseased neurons, remains unresolved.

We aim at elucidating the underlying mechanisms by analyzing the molecular machineries steering these processes, and by identifying new candidates and interaction partners involved in neuronal membrane dynamics. Here, we focus on the C₂ domain protein family of ferlins, which are membrane-anchored proteins orchestrating Ca²⁺-sensitive membrane dynamics in auditory synapses and muscle cells. Mutations in these proteins cause hearing impairment (otoferlin), muscular dystrophy (dysferlin and myoferlin) and cancer (myoferlin). A new research line aims at analyzing the role of C₂ domain dual-function proteins at membrane contact sites.

Methodologically, my group employs bottom-up approaches, studying membrane proteins reconstituted into artificial membranes as well as isolated organelles outside of their native cellular environment. This reductionist strategy allows us to precisely control parameters such as the ion and lipid composition, membrane curvature and tension, as well as the presence or absence of drug candidates, thereby enabling the dissection of factors critical for protein function. These approaches are integrated with biochemical and biophysical methodologies, alongside advanced electron microscopy techniques including single particle cryo electron microscopy and cryo electron tomography, and proteomics analyses.