Ph.D. Theses

Early impairments at the synaptic level can lead to disruption of communication between neurons, triggering neurological diseases such as schizophrenia. Emerging evidence has identified microglia as a key player in shaping synaptic architecture, but the precise mechanisms remain insufficiently understood.This study aims to investigate mechanisms of microglia-mediated synapse formation and elimination in two physiological contexts: first, during postnatal development, targeting microglia-complement interactions and second, during adult homeostasis examining microglia-synapse crosstalk via neurotransmitter signaling.The first objective used two-photon in vivo imaging to assess changes in synaptic density, microglial surveillance dynamics and microglia-synapse contact rates in a mouse model of complement protein overexpression, recapitulating hallmark phenotypes of schizophrenia. [...]

Mitochondria play vital roles in a variety of processes such as cellular metabolism, intracellular signalling and cell death. Defects in mitochondria can lead to inherited metabolic disorders and neurodegenerative diseases. [...]

In this cumulative thesis, I present my research on transcriptomic-based drug repurposing in human viral infections describing an optimized workflow for drug prediction, in vitro validation and in vivo studies in clinical cohorts based on three publications.In the first publication, I took lead in a larger team effort to introduce a newly designed drug repurposing approach based on whole blood transcriptomics data and drug signatures databases, which was applied to identify potential drug candidates for treatment of patients across COVID-19 severity groups stratified based on clinical parameters and transcriptomic phenotypes (Aschenbrenner et al. 2021). [...]

Tauopathies are neurodegenerative diseases characterised by the pathological folding of Tau into highly ordered, !3-sheet rich fibrils (so-called amyloid), which progressively spreadthrough the central nervous system in a prion-like manner. Despite extensive research, interand intracellular prion-like Tau aggregate formation and transmission mechanisms remainunresolved. [...]

Spatial navigation is an essential behavior for all moving life-forms. A main mammalian brain structure implicated in this process is the hippocampal formation. [...]

Tau protein is a microtubule associated protein present abundantly in the neurons of the central nervous system where it stabilizes the axonal microtubules thereby providing structural architecture for the axons of neurons. Aggregation of Tau occurs in many neurodegenerative diseases collectively termed tauopathies including Alzheimer disease (AD) and frontotemporal dementia (FTD). [...]

Tau is one of the microtubule associated proteins which can bind and stabilize microtubules. It is classified as a natively unfolded protein. [...]

Biological systems are ubiquitous, encompassing complex molecular networks governing single-cell organisms to expansive ecosystems profoundly impacting our planet's environment. In biology, the adoption of a systems approach seeks to achieve a comprehensive, quantitative understanding of living organisms comparable in some ways to the kind of understanding we have of systems in engineering and physics. [...]