Neuroscience
Term: 01.07.2023 – 30.06.2026
The development of a functional central nervous system depends on the accurate coordination of the highly dynamic microtubule cytoskeleton. Here we propose to chart the molecular landscape induced by mutations in microtubule cytoskeleton components implicated in neurodevelopmental disorders in human brain organoids to uncover unifying and diverging molecular features in a tissue-like context to design strategies to interfere with disease-phenotype progression.
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| Principal Investigator Dr. Sven Falk E-Mail: sven.falk@fau.de |
Term: 01.07.2023 – 30.06.2026
Specific regulation of protein degradation by the ubiquitin-proteasome system plays important roles in myelination, remyelination and neurodegenerative diseases. I want to analyse the functions of the deubiquitinase Otud7b in oligodendrocytes in vitro and in vivo in an oligodendrocyte-specific Otud7b knockout mouse model and identify functional targets of Otud7b in oligodendrocytes to deepen the understanding of posttranscriptional regulatory events during OL differentiation and CNS myelination.
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| Principal Investigator Dr. Melanie Küspert E-Mail: melanie.kuespert@fau.de |
An adverse local environment (“niche”) impairs the activity of neural stem cells (NSCs) in the adult brain. We investigate the new hypothesis that NSCs play an active role in generating favorable and adverse niche conditions. Specifically, we will investigate how dysfunctional NSCs generate adverse niche conditions focusing i) on the composition and the biomechanical properties of the extracellular matrix and ii) on NSC-derived exosomes and their composition.
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| Principal Investigator Prof. Dr. Dieter Chichung Lie E-Mail: chi.lie@fau.de | Principal Investigator Prof. Dr. Kristian Franze E-Mail: kristian.franze@fau.de |
Term: 01.04.2023 – 30.04.2026
Autosomal recessive mutations significantly contribute to intellectual disability and neurodevelopmental disorders (NDDs). However, high genetic heterogeneity of NDDs makes it difficult to prove pathogenicity. Using a comprehensive approach, we will combine genome sequencing and transcriptomics in a unique patient cohort of consanguineous Turkish families with at least two affected children, together with in silico analysis of candidates and in vivo screening in the Drosophila model organism.
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| Principal Investigator Prof. Dr. André Reis E-Mail: andre.reis@uk-erlangen.de | Principal Investigator Prof. Dr. Peter Soba E-Mail: peter.soba@fau.de |
Term: 01.06.2023 – 30.06.2026
Parkinson’s disease is a neurodegenerative movement disorder characterized by the progressive loss of midbrain dopaminergic (mDA) neurons. mDA neurons can be partitioned into numerous molecularly and functionally distinct neuronal subtypes. The molecular mechanisms orchestrating mDA neuron subtype specification are still largely unclear. This project will test the hypothesis that a temporal patterning program I recently uncovered contributes to the establishment of mDA neuron diversity.
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| Principal Investigator Dr. Andreas Sagner E-Mail: andreas.sagner@fau.de |
Term: 01.02.23 – 30.06.2026
Mutations in transcriptional corepressor CtBP1 cause the neurodevelopmental disorder HADDTS. Functional CtBP1 studies in the central nervous system so far focused on neurons. We recently found that CtBP1 is also important in oligodendrocytes. Here we will characterize the oligodendroglial functions of CtBP1 and the underlying cellular and molecular mechanisms in mice and a human ES cell-derived cellular disease model to show that defects in oligodendrogenesis and myelination contribute to HADDTS
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| Principal Investigator Prof. Dr. Michael Wegner E-Mail: michael.wegner@fau.de | Principal Investigator Prof. Dr. Anna Fejtova E-Mail: anna.fejtova@uk-erlangen.de |
Term: Not started yet
Heterozygous variants in the transcription factor SOX11 have been linked to a rare neurodevelopmental syndrome featuring intellectual disability and microcephaly. This project investigates the novel concept that SOX11 plays an essential role for mitotic spindle function through a non-transcriptional mechanism and that disruption of this mechanism contributes to the pathogenesis of SOX11-linked neurodevelopmental disorders.
Term: Not started yet
This project investigates the role of oligodendroglia in schizophrenia, focusing on neural circuit dysfunction using a mouse model of psychosis. It assesses oligodendroglial function and prefrontal sphingolipid metabolism during psychosis induction and treatment, examines the impact of myelination on neural coding in cognitive circuits and studies the excitability of oligodendroglia in behaving mice. This research aims to advance understanding of schizophrenia pathogenesis and treatment.
Term: Not started yet
Inflammatory bowel diseases impair gut neuro-immune circuits. While gut-innervating neurons are vulnerable to inflammation, satellite glia offer protection. Emerging evidence links glial plasticity to SOX10, but its regulation in gut-innervating ganglia remains unclear. We will investigate cytokine-driven modulation of SOX10 in glia of the myenteric, superior mesenteric, and dorsal root ganglia to uncover mechanisms of inflammation-induced plasticity and neuro-immune adaptation in colitis.
Term: Not started yet
Neurodegenerative disorders (NDs) frequently affect complex neurons with long axons. We hypothesize that axon length represents a molecularly defined source of intrinsic vulnerability to synapse loss, an early pathological feature of many NDs. We aim to identify these molecular signals, assay multiple ND-linked models and validate drivers of axon length-dependent synapse loss in human cells to provide insight into conserved molecular mechanisms as an entry point for early treatment of NDs.
Term: Not started yet
The molecular basis of motor neuron vulnerability in motor neuron diseases (MNDs) remains poorly understood. RNA dysregulation has been linked to MNDs, and LL-RNAs have recently been identified as a potentially critical component of neural longevity. We found an enrichment of long-lived RNAs (LL-RNAs) in human motor neurons. Thus, this project will investigate the mechanistic role of LL-RNAs in MNDs using brain organoids, aiming to identify novel biomarkers and therapeutic targets.