Biosketch

Prof. dr. Dirk-Jan Scheffers

Dirk-Jan Scheffers is a microbiologist (PhD 2001) specialized in bacterial cell biology. The research in his lab focuses on two lines: an applied line aimed at the development of novel pesticides for agriculture, and a fundamental line that aims to unravel the mechanisms of peptidoglycan synthesis. The fundamental line is the result of a career-long fascination on how bacteria grow and divide. Critical to these processes is the formation and splitting of peptidoglycan at the outside of the bacterial cell that proceeds in a very tightly regulated fashion. In this work, advanced molecular genetics and state-of-the-art microscopy are used to determine when, where, and by which proteins, precursor molecules are incorporated into the peptidoglycan layer.

The applied line arises from a long-standing (>10 years) collaboration of Scheffers with various Brazilian and Dutch partners (both academic and industrial), with the overall aim to develop new pesticides that can be used in agriculture (our model is orange trees and the disease Asiatic citrus canker) to replace the use of copper-based pesticides. Copper-based pesticides are cheap and effective, but have long term detrimental effects on crops, soil and ground water. Scheffers’ characterizes the mode of action of novel compounds and this expertise has also led to various new collaborations for the characterization of antimicrobials. Recent work has led to the identification of a series of active compounds, derived from natural compounds with antimicrobial activity, that have low toxicity, but really work in a greenhouse setting. The challenge now is to design formulation concepts for use in field tests under natural conditions (incl. tropical rain showers), and to monitor whether these novel formulations less affect crops, soil and ground water. This work has been consecutively funded by NWO and FAPESP (Sao Paulo, Brazil) with Scheffers as the leading scientists on the Dutch side.

Three top publications 2017-2022

1. Zielińska A., Savietto A., Sousa Borges A., …… Bramkamp M & Scheffers D.-J. (2020) Flotillin-mediated membrane fluidity controls peptidoglycan synthesis and MreB movement. eLife 9: e57179 DOI: https://doi.org/10.7554/eLife.57179

This was the first paper to show that there is a protein-mediated mechanism of membrane fluidity control. This mechanism is responsible for keeping the membrane sufficiently fluid to allow processive peptidoglycan synthesis by a membrane anchored protein complex.

2. Morão L.G., Polaquini C.R. …… Scheffers D.-J., Regasini L.O. & Ferreira H. (2019) A simplified curcumin targets the membrane of Bacillus subtilis. MicrobiologyOpen 8 (4): e00683 DOI: https://onlinelibrary.wiley.com/doi/full/10.1002/mbo3.683

This paper is an example of a mode of action study of a antimicrobial based on a natural compound.

3. Morales Angeles D., Liu Y., …… Hirsch A.K.H. & Scheffers D.-J. (2017) Pentapeptide‐rich peptidoglycan at the Bacillus subtilis cell‐division site. Molecular Microbiology 104: 319-333 DOI: https://onlinelibrary.wiley.com/doi/full/10.1111/mmi.13629

This paper showed that extensive labeling of peptidoglycan, observed when bacterial cells divide, is not (only) the result of increased synthesis activity, but much more a mark of the absence of cross-linking. This facilitates splitting of the wall during the actual separation of cells.