Biology subjects

Halatek, J.

Publications and source records attributed to Halatek, J..

4 recordsLinked to original sources

bioRxiv2020

Adaptability and evolution of the cell polarization machinery in budding yeast

How can a self-organized cellular function evolve, adapt to perturbations, and acquire new sub-functions? To make progress in answering these basic questions of evolutionary cell biology, we analyze, as a concrete example, the cell polarity machinery of Saccharomyces cerevisiae. This cellular module exhibits an intriguing resilience: it remains operational under genetic perturbations and recovers quickly and reproducibly from the deletion of one of its key components. Using a combination of modeling, conceptual theory, and experiments, we show that multiple, redundant self-organization mechanisms coexist within the protein network underlying cell polarization and are responsible for the modules resilience and adaptability. Based on our mechanistic understanding of polarity establishment, we hypothesize how scaffold proteins, by introducing new connections in the existing network, can increase the redundancy of mechanisms and thus increase the evolvability of other network components. Moreover, our work suggests how a complex, redundant cellular module could have evolved from a more rudimental ancestral form.

evolutionary biology↗

bioRxiv2020

Bulk-surface coupling reconciles Min-protein pattern formation in vitro and in vivo

Self-organisation of Min proteins is responsible for the spatial control of cell division in Escherichia coli, and has been studied both in vivo and in vitro. Intriguingly, the protein patterns observed in these settings differ qualitatively and quantitatively. This puzzling dichotomy has not been resolved to date. Using reconstituted proteins in laterally wide microchambers with a well-controlled height, we show that the Min protein dynamics on the membrane crucially depend on bulk gradients normal to the membrane. A theoretical analysis shows that in vitro patterns at low bulk height are driven by the same lateral oscillation mode as pole-to-pole oscillations in vivo. At larger bulk height, additional vertical oscillation modes set in, marking the transition to a qualitatively different in vitro regime. Our work qualitatively resolves the Min systems in vivo/in vitro conundrum and provides important insights on the mechanisms underlying protein patterns in bulk-surface coupled systems.

biophysics↗

bioRxiv2019

Design of biochemical pattern forming systems from minimal motifs

Although molecular self-organization and pattern formation are key features of life, only very few pattern-forming biochemical systems have been identified that can be reconstituted and studied in vitro under defined conditions. A systematic understanding of the underlying mechanisms is often hampered by multiple interactions, conformational flexibility and other complex features of the pattern forming proteins. Because of its compositional simplicity of only two proteins and a membrane, the MinDE system from Escherichia coli has in the past years been invaluable for deciphering the mechanisms of spatiotemporal self-organization in cells. Here we explored the potential of reducing the complexity of this system even further, by identifying key functional motifs in the effector MinE that could be used to design pattern formation from scratch. In a combined approach of experiment and quantitative modeling, we show that starting from a minimal MinE-MinD interaction motif, pattern formation can be obtained by adding either dimerization or membrane-binding motifs. Moreover, we show that the pathways underlying pattern formation are recruitment-driven cytosolic cycling of MinE and recombination of membrane-bound MinE, and that these differ in their in vivo phenomenology.

biophysics↗

bioRxiv2018

PAR protein activation-deactivation cycles stabilize long-axis polarization in C. elegans

In the Caenorhabditis elegans zygote, PAR protein patterns, driven by mutual anatagonism, determine the anterior-posterior axis and facilitate the redistribution of proteins for the first cell division. Yet, the factors that determine the selection of the polarity axis remain unclear. We present a reaction-diffusion model in realistic cell geometry, based on biomolecular reactions and accounting for the coupling between membrane and cytosolic dynamics. We find that the kinetics of the phosphorylation-dephosphorylation cycle of PARs and the diffusive protein fluxes from the cytosol towards the membrane are crucial for the robust selection of the anterior-posterior axis for polarisation. The local ratio of membrane surface to cytosolic volume is the main geometric cue that initiates pattern formation, while the choice of the long-axis for polarisation is largely determined by the length of the aPAR-pPAR interface, and mediated by processes that minimise the diffusive fluxes of PAR proteins between cytosol and membrane.

biophysics↗