Host Microbe Interactions - AG Jabs

Sabrina Jabs

Host Microbe Interactions

Sabrina Jabs

Group Leader

Sabrina Jabs


Anna Gegautzke

Welcome to the Host Microbe Interactions Group

We are interested in host-microbe interactions, which includes studying the influence of the microbiota on host physiology and possible consequences for developing diseases, and the mechanisms bacterial and viral pathogens use to manipulate the host to favor infection. We are primarily interested in the role of RNA epitranscriptome modifications in these processes, but also study select aspects of intracellular protein trafficking in this context.

Research Projects

Epitranscriptome modifications in Host Microbe Interactions

Commensal bacteria, in particular the gut microbiota, have profound effects on host physiology, including host metabolism, intestinal morphology, or the development of the immune system. Dysbiosis of the microbiota, but also select bacterial species, can influence the development of multiple diseases, such as inflammatory bowel disease, colorectal cancer, diabetes or metabolic syndrome. We are interested in mechanisms by which commensal bacteria and their metabolites influence disease development by modulating gene expression in host tissues.

Our attention is focused on epitranscriptomic modifications, i.e. post-transcriptional mRNA modifications such as N6-methyladenosine (m6A), that have been shown to be important regulators of mRNA fate. We are studying how these modifications are influenced by commensal and pathogenic bacteria and examine the physiological relevance of mRNA modifications in the context of select inflammatory diseases applying state-of-the art cell biology, imaging, RNA-sequencing and single cell sequencing approaches to study cellular, organoid and gnotobiotic and transgenic animal models. Read more about the influence on  the microbiota on epitranscriptome modifications here.

Dynamic regulation of m6A modifications by methyltransferase (‘writer’) complexes and demethylases (‘erasers’). m6A modifications are recognized by m6A-binding proteins (‘readers’). Modified from Zhao et al. 2017 Nature Reviews Molecular Cell Biology.

Regulation of Lysosome Biogenesis in Health and Disease

Lysosomes are key degradative compartments of the cell and have emerged as metabolic signalling hub in the past decade. Lysosome dysfunction results in both rare and more common disorders. Certain viruses, such as Ebola Virus and SARS-CoV-2, use the degradative function of lysosomes to gain entry into the cell and start their infection cycle.

A plethora of membrane proteins and transporters and more than 60 lysosomal hydrolases are required for proper functioning of lysosomes. The majority of lysosomal hydrolases are tagged with mannose 6-phosphate (M6P) moieties by the GlcNAc-1-phosphotransferase complex. We are interested in identifying novel regulators of M6P-dependent protein trafficking from the Golgi apparatus to lysosomes, which is prerequisite for lysosome biogenesis, using genome-wide genetic screens and targeted approaches. We study the molecular functions of these regulators using high-resolution microscopy, proteomics and biochemical methods in cellular, organoid and animal models of human diseases. Understanding the mechanisms of lysosomal biogenesis has implications for inherited diseases, pathogen infections and metabolic adaptations in cancer. Therefore, deeper insights into these mechanisms may help to develop novel therapeutic strategies.

We recently identified LYSET, a novel regulator of M6P-trafficking of lysosomal hydrolases with implications for an inherited human disease, viral infections and tumor growth (Richards*, Jabs*, Qiao* et al. Science 2022 and Pechincha et al. Science 2022). Read more about LYSET here.

The group is always interested in motivated students to conduct their bachelor, master or MD thesis.

There’s currently an MD fellowship funded by the Research Traning Group RTG2771 Humans and Microbes available. Please get in touch for more information.

Main Projects / Funding

Selected Publications