We focus on the bioinformatic analysis and integration of state-of-the-art functional genomics data that we obtain through close collaboration with experimental biologists (genome sequences, gene and protein expression, metabolomics, Tn-seq data).
Complete, de novo assembled genomes are an optimal basis for functional genomics studies. We aim to identify all proteins encoded in a genome by proteogenomics, including small proteins that are often missed (e.g., antimicrobial peptides), thereby improving genome annotations. We also study the role of microbiome isolates – e.g. for plant protection – by applying metagenomic, comparative genomic and transcriptomic approaches. Finally, we aim to understand biofilm-mediated antibiotic resistance.
We co-authored a best practices paper on mass spectrometry-based proteomics and computational approaches to identify genes encoding small proteins (≤ 50 to 100 amino acids), which are often under-represented/missed in current genome annotations. Such small proteins have recently received widespread interest as some play critical roles in cellular functions, e.g. cellular communication, signaling, virulence, antibiotic resistance, metabolism. Our proteogenomics strategy and public web service support their discovery.
Moreover, we contributed our genome assembly expertise to our long-term collaborator Prof. Fischer (ETHZ) who works on rhizobial symbioses, which play a major role for sustainable agriculture. The study allowed to elucidate the function of individual and combinations of sensor histidine kinase mutants (overall 11 family members) and is of general interest how cellular functions of complex gene families can be dissected. Finally, we contributed to a study of a JPIAMR- financed consortium that aims to identify relevant mechanisms of action in biofilms that could be targeted by novel anti-microbials.
Ahrens CH et al. A Practical Guide to Small Protein Discovery and Characterization Using Mass Spectrometry. J Bacteriol. 2022, 204:e0035321. /10.1128/JB.00353-21
Wülser J et al. Salt- and Osmo-Responsive Sensor Histidine Kinases Activate the Bradyrhizobium diazoefficiens General Stress Response to Initiate Functional Symbiosis. Mol Plant Microbe Interact. 2022, 35:604-615. /10.1094/MPMI-02-22-0051-FI
Valentin, JDP et al. Role of the flagellar hook in the structural development and antibiotic tolerance of Pseudomonas aeruginosa biofilms. ISME J. 2022, 16:1176-1186. /10.1038/s41396-021-01157-9