Mechanisms of Self-organisation within Bacterial Cells
Dr. Sean Michael Murray
Spatial organisation is critical for all life. Many cellular processes such as chromosome segregation, cell division and motility require the timely positioning of proteins or chromosomal loci to specific locations within the cell and this is just as true for bacteria as it is for eukaryotes. Such spatial organisation is often due to the presence of existing cellular landmarks or spatial cues but there are many examples in which proteins or DNA appear to be actively and dynamically positioned to specific locations. This occurs in spite of the homogenising effect of diffusion.
We use bacteria as tractable model systems in which to uncover the principles and mechanisms underlying such organisation. To this end, we use mathematical modelling and stochastic simulations combined with live-cell experiments and genetics in a multi-disciplinary and systems approach. The fundamental principles we uncover will help our understanding of self-organisation across all living systems.
One current focus is on the self-positioning of the bacterial Structural Maintenance of Chromosomes (SMC) complex MukBEF in Escherichia coli and its role in chromosome segregation. In short cells, MukBEF forms a dynamic nucleoid-associated cluster that is specifically positioned at mid-cell. During cell growth the cluster splits and is re-positioned to the cell quarter positions. We are interested in understanding the mechanism behind this self-positioning both from a theoretical and experimental standpoint. Furthermore, MukBEF has been implicated in the positioning and segregation of chromosomal origins and we are currently investigating this exciting possibility, using a combination of simulations, genetics and microscopy.
Seán M. Murray†, Martin Howard† (2019).
Centre-Finding in E. coli and the Role of Mathematical Modelling: Past, Present and Future, Journal of Molecular Biology, https://doi.org/10.1016/j.jmb.2019.01.017, [arXiv: 1901.06139]
Andreas Hofmann, Jarno Mäkelä, David Sherratt, Dieter Heermann, Seán M. Murray† (2018).
Self-organised segregation of bacterial chromosomal origins, Biorxiv, https://doi.org/10.1101/304600
Max Mundt, Alexander Anders, Seán M. Murray, Victor Sourjik (2018).
A system for gene expression noise control in yeast, ACS Synthetic Biology, Article ASAP, https://doi.org/10.1021/acssynbio.8b00279
Mathilde Guzzo*, Seán M. Murray*, Eugenie Martineau*, Sébastien Lhospice*, Grégory Baronian, Laetitia My, Yong Zhang, Leon Espinosa, Renaud Vincentelli, Benjamin Bratton, Joshua Shaevitz, Virginie Molle, Martin Howard†, Tâm Mignot† (2018).
A gated relaxation oscillator mediated by FrzX controls morphogenetic movements in Myxococcus xanthus, Nature Microbiology, 3, 948-959 https://doi.org/10.1038/s41564-018-0203-x
Seán M. Murray†, Victor Sourjik (2017).
Self-organisation and positioning of bacterial protein clusters, Nature Physics, 13, 1006-1013. https://doi.org/10.1038/nphys4155
Katrin Schenk, Marc Eisemann, Ana B. Hervás, Bernhard A. Schmitt, Stephan Dahlke, Luise Kleine Borgmann, Seán M. Murray, Peter L. Graumann† (2017).
Rapid turnover of DnaA at replication origin regions contributes to initiation control of DNA replication, PLoS Genetics, 13(2): e1006561. https://doi.org/10.1371/journal.pgen.1006561
David J. Leslie, Christian Heinen, Frederic D. Schramm, Marietta Thüring, Christopher D. Aakre, Sean M. Murray, Michael T. Laub, Kristina Jonas† (2015).
Nutritional Control of DNA Replication Initiation through the Proteolysis and Regulated Translation of DnaA, PLoS Genetics 11(7): e1005342. https://doi.org/10.1371/journal.pgen.1005342
Seán M. Murray*, Gaël Panis*, Coralie Fumeaux, Patrick H. Viollier†, Martin Howard† (2013).
Computational and Genetic Reduction of a Cell Cycle to Its Simplest, Primordial Components, PLoS Biology 11 (12): e1001749. https://doi.org/10.1371/journal.pbio.1001749