Microbial Proteomics

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Microbes are by far the most abundant organisms living on our planet, outnumbering the human population by more than 1020 times. Even our own body is populated by 10 times more microbial than human cells. In the light of such numbers it becomes apparent, that we will always have to deal with all microbial life forms that surround us, and that we have to share living space and resources. Therefore, a thorough understanding of microbial physiologies, infection and defense systems, metabolic processes or survival strategies are of great interest in order to actively defeat or cultivate microorganism.

Our group works on microorganisms, on the one hand as model organisms and for technology development, on the other hand because of their clinical relevance. We currently focus on Saccharomyces cerevisiae, Mycobacterium tuberculosis, Streptococcus pyogenes, as well as various viruses. In recent years, for most of these microbes we have generated comprehensive, high quality assay repositories for the sensitive detection and relative as well as absolute quantification of virtually all annotated proteins using targeted mass spectrometric techniques like SRM or SWATH-MS.

Microbial proteomics  
Workflow used to generate proteome-wide reference assays for the M. tuberculosis proteome.

In the context of M. tuberculosis we use these unique resources to improve genome annotation by proteogenomic analysis, as well as to study protein-level responses to different stress conditions, such as starvation and oxygen depletion, which causes a transition into a clinically relevant dormant state. Further, we are interested in elucidating host-pathogen interactions upon infection of human cells, such as altered protein expression in M. tuberculosis, as well as changes in the human MHC peptidome.

In the case of S. pyogenes our aim is to identify and understand virulence factors by integrating genomic, proteomic, and phenotypic data of clinically isolated S. pyogenes strains. Specifically, we aim to understand how genomic variation may lead to differences in proteome expression and ultimately differences in phenotype (virulence).

Our research interests in the smallest eukaryotic model organism S. cerevisiae are multifaceted. One focus is on the better understanding of metabolic regulation and adaptation upon changing nutritional conditions based on protein abundance changes as well as phosphoproteomic analyses. Further, we are interested in the phosphorylation-based signaling networks, including for example the TOR pathway and the pheromone pathway. Also the regulation of gene expression by transcriptional regulatory elements we investigate using targeted mass spectrometry. Finally, we use yeast as a model organism to study how genetic loci are influencing the levels of related proteins by quantitative trait loci analysis (QTLs).

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