Neurosciences

Main Research: Neurosciences

Term: 16.11.2020 – 15.05.2023

sALS is a motor neuron disease where pathological insoluble states of TDP-43, an alternative splicing (AS) factor are found. Dysregulated AS is detected, but it is unknown whether TDP-43 aggregation is causative for this. We develped an iPSC-derived model of sALS where AS changes in this system are not dependent on TDP-43. We propose to investigate pathological mechanisms of new AS factors in sALS using proteomics and NGS approaches and subsequent validation in sALS post mortem tissue.

Principal Investigator Dr. Florian Krach e-mail: Florian.Krach@uk-erlangen.de

Main Research: Neurosciences

Term: 01.07.2021 – 31.12.2023

Multiple system atrophy (MSA) is characterized by neurodegeneration and neuroinflammatory response of myeloid cells. The goal of this project is to decipher the role of microglia in disease mechanisms of MSA. Depletion of microglia results in improved survival, however, also in behavioural motor deficits in a MSA mouse model. Structural, biochemical and transcriptional approaches will be used to characterize changes in neuronal connectivity and synaptic networks upon microglia depletion in MSA.

Main Research: Neurosciences

Term: Not started yet

Alcoholism and depression are highly comorbid disorders. Neutral sphingomyelinase (NSM) is suggested as a missing link between emotional status and alcohol consumption due to the downstream effects on the serotoninergic system. A new line of mice with NSM gene knockout specifically in the brain serotoninergic system was created to investigate if the interaction between NSM and the brain serotoninergic system determines the comorbidity between negative emotional state and alcohol consumption.

Main Research: Neurosciences

Term: Not started yet

Inflammatory bowel disease (IBD) predisposes for synucleinopathies like Parkinson Disease. This is putatively caused by propagation of chronic inflammation into the brain. The hypothesis of this project is that chronic inflammation in IBD activates microglia in distinct brain regions, thereby mediating neuronal pathology and aggravating synucleinopathy. This hypothesis will be tested in post mortem brain tissue of IBD patients and mice with colitis.

Main Research: Neurosciences

Term: Not started yet

Proper Schwann cell development and myelination are essential for a functional peripheral nervous system and regulated by networks of chromatin modifiers and transcription factors. Here I plan to study the role of the acetyltransferase Tip60 as part of the Tip60/Ep400 chromatin remodeling complex in lineage progression and myelination by characterizing its target genes and interaction with transcription factor Sox10. Results may help to better understand peripheral neuropathies.