Ph.D. Theses

Mutations in genes that control epigenetic gene expression, especially the machinery that controls Histone 3 lysine 4 (H3K4me) methylation, are over-represented in intellectual disability disorders. It is mediated by both lysine methyltransferases and demethylases. [...]

Histone modifications and gene expression are tightly regulated processes in the brain that has been shown to play crucial role from the beginning of brain development, learning-memory formation and aging. While brain comprises of numerous types of neurons and non-neuronal cells, this regulation is highly cell type specific. [...]

Synaptic plasticity is how neurons adapt to new stimuli and necessitates changes in synaptic weight. For these changes to be durable, local translation in neurites, and at pre- and post-synapses is required. [...]

Dementia is the most significant health challenge in modern times, currently affecting over 50 million people worldwide. The number of people afflicted with this disorder is on the rise and expected to double by 2025. [...]

AIMS AND BACKGROUND: Besides Alzheimer’s disease (AD), Vascular dementia (VD) caused by cerebral small vessel disease (CSVD) is one of the most common causes of dementia but differential diagnosis, especially the discrimination of VD and AD, is still difficult. Established imaging markers of VD (e.g. [...]

Abstract: This thesis covers a very broad range of bioinformatics methods ranging from the development of the analysis pipeline to the data integration and development of an expression atlas (database and web application development). In addition, an in silico method was developed to annotate genome with novel features, and predicting diseases based on the expression profiles. [...]

Of all neurodegenerative diseases, Alzheimer´s Disease is the most widespread dementia syndrome, exhibiting progressive memory loss and intellectual abilities. One of the pathological hallmarks of this disease is associated to the presence of abundant intracellular deposits of the Tau protein. [...]

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). [...]