Two Projects (Jörg Stülke)
Project 1
The essence of life – contributions of so far unknown proteins
Understanding cellular life requires a comprehensive knowledge of the essential cellular functions, the components involved, and their interactions. Minimized genomes are an important tool to gain this knowledge. In this project, we want to construct a minimized genome of the Gram-positive model bacterium Bacillus subtilis with the aim of identifying the protein and RNA molecules that are essential for growth of B. subtilis, their functions, and interactions. At the end, we aim at constructing a strain that we designate MiniBacillus (www.minibacillus.org). The main questions are:
1) Which genes and proteins have to be part of a minimal cell, and which components are dispensable?
2) How are the individual essential cellular functions organized?
3) How do the gene expression and metabolic networks adapt to the genome minimization?
4) How do the cells respond to genome minimization by the acquisition of mutations?
So far, we have reduced the genome of B. subtilis by more than 40% which is the most advanced genome reduction for any complex organism. We will now put the focus on highly expressed unknown proteins and their functions. Judged from their strong expression, such proteins are likely to play a key role for the physiology of the organism. We will combine unbiased interaction studies with mutant analyses and biochemical experiments.
Homepage Research Group
http://genmibio.uni-goettingen.de/
For more information see for instance:
Reuß, D. R., Altenbuchner, J., Mäder, U., Rath, H., Ischebeck, T., Sappa, P. K., Thürmer, A., Guérin, C., Nicolas, P., Steil, L., Zhu, B., Feussner, I., Klumpp, S., Daniel, R., Commichau, F. M., Völker, U., & Stülke, J. (2017) Large-scale reduction of the Bacillus subtilis genome: consequences for the transcriptional network, resource allocation, and metabolism. Genome Res. 27: 289-299.
O’Reilly, F. J., Graziadei, A., Forbrig, C., Bremenkamp, R., Charles, C., Lenz, S., Elfmann, C., Fischer, L., Stülke, J., & Rappsilber, J. (2023) Protein complexes in cells by AI-assisted structural proteomics. Mol. Syst. Biol. 19: e11544.
Wicke, D., Meißner, J., Warneke, R., Elfmann, C., & Stülke, J. (2023) Understudied proteins and understudied functions in the model organism Bacillus subtilis – a major challenge in current research. Mol. Microbiol. 120: 8-19.
Wicke, D., Neumann, P., Gößringer, M., Chernev, A., Davydov, S., Poehlein, A., Daniel, R., Urlaub, H., Hartmann, R. K., Ficner, R., & Stülke, J. (2024) The previously uncharacterized RnpM (YlxR) protein modulates the activity of ribonuclease P in Bacillus subtilis in vitro. Nucleic Acids Res. 52:1404-1410.
Project 2
Data integration in the era of artificial intelligence
Understanding cellular life requires a comprehensive knowledge of the essential cellular functions, the components involved, and their interactions. We are interested in the comprehensive understanding of the Gram-positive model bacterium Bacillus subtilis with the aim of identifying the protein and RNA molecules that are essential for growth of B. subtilis, their functions, and interactions. At the end, we aim at constructing a strain that we designate MiniBacillus (www.minibacillus.org). This large project integrates experimental and bioinformatic projects.
To facilitate the generation of hypotheses on the possible functions of unknown proteins, we have developed a database that aims at integrating all available information. This database, SubtiWiki, is used worldwide in labs that study Gram-positive bacteria, including those that are important pathogens or relevant for biotechnological applications.
In this particular project we want to further develop the database with a focus on RNA molecules, their roles and interactions. moreover, we want to apply novel AI tools to predict structures of proteins and protein complexes with the aim of providing hypotheses for further experimental investigation.
Homepage Research Group
http://genmibio.uni-goettingen.de/
https://subtiwiki.uni-goettingen.de/v5/welcome
For more information see for instance:
Reuß, D. R., Altenbuchner, J., Mäder, U., Rath, H., Ischebeck, T., Sappa, P. K., Thürmer, A., Guérin, C., Nicolas, P., Steil, L., Zhu, B., Feussner, I., Klumpp, S., Daniel, R., Commichau, F. M., Völker, U., & Stülke, J. (2017) Large-scale reduction of the Bacillus subtilis genome: consequences for the transcriptional network, resource allocation, and metabolism. Genome Res. 27: 289-299.
Elfmann, C. & Stülke, J. (2023) PAE Viewer: A webserver for the interactive visualization of the predicted aligned error for multimer structure predictions and crosslinks. Nucleic Acids Res. 51: W404-W410.
Stülke, J., Grüppen, A., Bramkamp, M. & Pelzer, S. (2023) Bacillus subtilis, a swiss army knife in science and biotechnology. J. Bacteriol. 205: e00102-23.
O’Reilly, F. J., Graziadei, A., Forbrig, C., Bremenkamp, R., Charles, C., Lenz, S., Elfmann, C., Fischer, L., Stülke, J., & Rappsilber, J. (2023) Protein complexes in cells by AI-assisted structural proteomics. Mol. Syst. Biol. 19: e11544.
Stahl, K., Warneke, R., Demann, L., Bremenkamp, R., Hormes, B., Brock, O., Stülke, J. & Rappsilber, J. (2024) Modelling protein complexes with crosslinking mass spectrometry and deep learning. Nat. Commun. 15: 7866.
Elfmann, C., Dumann, V., van den Berg, T., & Stülke, J. (2025) A new framework for SubtiWiki, the database for the model organism Bacillus subtilis. Nucleic Acids Res. In press. https://doi.org/10.1101/2024.09.10.612211.