Molecular & Functional Neurobiology Group

The Molecular & Functional Neurobiology group at the LCSB

From left to right: Kobi Wasner, Nassima Ouzren, Léa Grandmougin, Dr. Anne Grünewald, Jenny Ghelfi, Dr. Sandro Pereira

About the Molecular & Functional Neurobiology Group

The main goal of the Molecular and Functional Neurobiology group is to understand the mechanisms that underlie movement disorders, such as Parkinson’s disease (PD) or Myclonus Dystonia (M-D). We apply molecular, ‘omics’ and single-cell approaches to postmortem brain tissue and iPSC-derived neuronal cultures to decipher genetic and non-genetic origins of such diseases.

For PD, in the majority of patients, no genetic cause can be identified. We therefore explore the role of the mitochondrial genome in pathogenesis of these so-called idiopathic cases using postmortem and iPSC-derived tissue. Somatic changes affecting the integrity and replication of the mitochondrial DNA (mtDNA) in dopaminergic neurons are likely part of the disease process. Employing laser-capture microdissection, RNA-sequencing and quantitative immunofluorescence, we aim to identify the cellular pathways linked to mtDNA disintegration in idiopathic PD. Such novel pathways may be the targets for therapeutic intervention in the future.

For those cases of PD that have a genetic origin, we are targeting cellular factors that are associated with penetrance, i.e. that determine the likelihood that an individuals carrying a certain gene variant also develops the disease. These biomarkers may either serve to indicate advanced disease progression or they may, ideally, also direct us to cellular processes that can be modulated by drugs to delay the onset of PD.

Beyond PD, the Molecular and Functional Neurobiology group is also studying the cellular mechanisms underlying M-D using iPSC-derived patient neurons. This work is performed in close collaboration with Institute of Neurogenetics at the University of Lübeck (Germany).     

The Molecular and Functional Neurobiology group was established under the auspices of the Luxembourg National Research Fund's ATTRACT Programme.