Doctoral Candidate Position 8 - University of Aarhus, Denmark
Investigating molecular mechanisms underlying the Sex dimorphism in the immune response in Parkinson's disease.
Felix Buchner, MSc is our BICEPS Fellow at Aarhus University's Department of Biomedicine, working in the Romero-Ramos Lab. His project bridges in vitro and in vivo systems to explore sex-specific neuroimmune mechanisms in Parkinson's disease, combining hiPSC-derived microglia and neurons in adherent and 3D-cell culture, rodent models of neurodegeneration, behavioral assays, multi-omics, and post-mortem human tissue. This translational work aims to uncover how immune dimorphism shapes disease progression in a sex-specific way.
Before starting his fellowship, Felix worked as a Staff Scientist at the DZNE Dresden, where he developed the CASCO method, improving hiPSC-derived spinal organoid motor neuron patterning approaches by introducing a more physiologically relevant axial resolution of cells. He co-authored multiple publications, including one first-author paper on spinal cord organoid development (Buchner et al., 2024, bioRxiv), a collaborative study on spinal development in Spinal Muscular Atrophy (Grass et al., 2024, Cell Reports Medicine), and a review on spinal cord hiPSC-derived organoids (Buchner et al., 2023, Life). His previous work was supported by a DGM e.V. Research Grant and included strong collaboration with Qkine Ltd. on growth-factor optimization and testing. At the MPI-CBG Dresden, Felix worked as Senior Research Technician at the Organoid and Stem Cell Facility, developing pipelines for hiPSC quality control, reprogramming, and organoid differentiation. He holds an MSc in Regenerative Biology and Medicine from TU Dresden and the Center for Regenerative Therapies Dresden (CRTD), and a BSc in Biological Sciences from FAU Erlangen-Nuernberg, where his research focused on developmental biology in Xenopus laevis.
In summary, his academic path included multiple research internships in neurobiology, immunology, and organoid systems at TU Dresden and FAU Erlangen, where he refined his expertise in molecular biology, bioimaging, and stem-cell models, now transitioning into hybrid-projects.
Description of project
The risk to develop Parkinson's disease is higher in male than female. Moeover, the presentaion fo the disease differes between sexes. Microgliosis is a common pathological observation in the brain of people with Parkinson's disease. Novel unpublished AU data from an α-synuclein based PD model using single cell RNA sequencing showed a significant difference between sexes in the immune response in brain (microglia and macrophages). We believe this immune sex-dimorphism relates to the higher PD risk seen in males. To explore this we will analyse and compare the existing data in the PD rodent model with relevant human databases and selected transcript confirmed/validated in vitro using human male and female (iPSC-derived). The significance of the selected differentially regulated genes will be confirmed using in vitro assays and the potential neuroprotection tested in vivo by using transgenic or knock-out mice. α-synuclein pathology, neurodegeneration and central and peripheral immune responses will be evaluated. The project integrates techniques from in vivo modelling, and cell culture, histology and advanced microscopy, flow cytometry and other single cell techniques providing a multidisciplinary approach to investigating immune regulation in PD. Ultimately, this work could lead to the identification of novel drugs that modulate, offering potential new avenues for treating PD and related disorders.