Molecular Immunology in Neurodegeneration

Priv.-Doz. Dr. Marc Beyer

Areas of investigation/research focus

The group of Dr. Beyer is highly interested in unraveling the molecular events in innate and adaptive immune cells resulting in their activation and functional reprogramming contributing to the development of neurodegenerative disorders.

One main research focus is the characterization of regulatory T cells, T cell differentiation and T cell exhaustion. Seminal work of the group could show the importance of the chromatin remodeler special AT-rich binding protein 1 (Satb1) for the function of Treg cells and peripheral T cells and its influence on the development of autoimmunity. Furthermore, the group could show that chronic exposure to the proinflammatory cytokine TNF can be causative for T cells dysfunction in chronic viral infections. Following up on these observations, the group is currently assessing the importance of T cells for CNS pathology.

An additional research focus is the understanding of myeloid cell activation and differentiation. Here the group contributed over the last years to our understanding of myeloid cell polarization and dendritic cell development. Together with colleagues in New York and Vienna the group could recently describe how early embryonic macrophages settle tissues and receive tissue derived signals to differentiate into microglia and tissue-associated macrophages. Current interests concentrate on the transcriptional and epigenetic characterization of microglia in neurodegenerative diseases.

A longstanding interest of the group has been to characterize the role of important transcription factors and chromatin remodelers for the development and differentiation of T cells. Here, the group has recently identified a novel transcription factor specifically expressed in Treg cells and characterized a novel suppressor mechanisms particularly important in adipose tissue. Loss of the major prostaglandin E2 metabolizing enzyme in Treg cells results in the development of insulin resistance through accumulation of non-functional Treg cells.

High-throughput single-cell approaches, both on protein (multi-parameter flow cytometry, >30) and transcriptomic level (single-cell RNA-seq), are key technologies the group is using to characterize cellular heterogeneity and identify important cell subpopulations and developmental pathways contributing to immune responses. We now want to establish the combination of sigle-cell Omics with multi-parameter flow cytometry as a model for 1) the discovery and validation of cellular heterogeneity during neurodegeneration and 2) the identification of key molecular drivers of the pathological process.

In addition, the group is highly active in the application of genetic engineering using TALEN and CRISPR/Cas9 technology to perform gain- and loss-of-function experiments, specifically perturbing transcription, and identifying genomic regulatory elements contributing to repression or enhancement of gene expression.

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