@article{12152,
  abstract     = {ESCRT-III filaments are composite cytoskeletal polymers that can constrict and cut cell membranes from the inside of the membrane neck. Membrane-bound ESCRT-III filaments undergo a series of dramatic composition and geometry changes in the presence of an ATP-consuming Vps4 enzyme, which causes stepwise changes in the membrane morphology. We set out to understand the physical mechanisms involved in translating the changes in ESCRT-III polymer composition into membrane deformation. We have built a coarse-grained model in which ESCRT-III polymers of different geometries and mechanical properties are allowed to copolymerise and bind to a deformable membrane. By modelling ATP-driven stepwise depolymerisation of specific polymers, we identify mechanical regimes in which changes in filament composition trigger the associated membrane transition from a flat to a buckled state, and then to a tubule state that eventually undergoes scission to release a small cargo-loaded vesicle. We then characterise how the location and kinetics of polymer loss affects the extent of membrane deformation and the efficiency of membrane neck scission. Our results identify the near-minimal mechanical conditions for the operation of shape-shifting composite polymers that sever membrane necks.},
  author       = {Jiang, Xiuyun and Harker-Kirschneck, Lena and Vanhille-Campos, Christian Eduardo and Pfitzner, Anna-Katharina and Lominadze, Elene and Roux, Aurélien and Baum, Buzz and Šarić, Anđela},
  issn         = {1553-7358},
  journal      = {PLOS Computational Biology},
  keywords     = {Computational Theory and Mathematics, Cellular and Molecular Neuroscience, Genetics, Molecular Biology, Ecology, Modeling and Simulation, Ecology, Evolution, Behavior and Systematics},
  number       = {10},
  publisher    = {Public Library of Science},
  title        = {{Modelling membrane reshaping by staged polymerization of ESCRT-III filaments}},
  doi          = {10.1371/journal.pcbi.1010586},
  volume       = {18},
  year         = {2022},
}

@article{8997,
  abstract     = {Phenomenological relations such as Ohm’s or Fourier’s law have a venerable history in physics but are still scarce in biology. This situation restrains predictive theory. Here, we build on bacterial “growth laws,” which capture physiological feedback between translation and cell growth, to construct a minimal biophysical model for the combined action of ribosome-targeting antibiotics. Our model predicts drug interactions like antagonism or synergy solely from responses to individual drugs. We provide analytical results for limiting cases, which agree well with numerical results. We systematically refine the model by including direct physical interactions of different antibiotics on the ribosome. In a limiting case, our model provides a mechanistic underpinning for recent predictions of higher-order interactions that were derived using entropy maximization. We further refine the model to include the effects of antibiotics that mimic starvation and the presence of resistance genes. We describe the impact of a starvation-mimicking antibiotic on drug interactions analytically and verify it experimentally. Our extended model suggests a change in the type of drug interaction that depends on the strength of resistance, which challenges established rescaling paradigms. We experimentally show that the presence of unregulated resistance genes can lead to altered drug interaction, which agrees with the prediction of the model. While minimal, the model is readily adaptable and opens the door to predicting interactions of second and higher-order in a broad range of biological systems.},
  author       = {Kavcic, Bor and Tkačik, Gašper and Bollenbach, Tobias},
  issn         = {1553-7358},
  journal      = {PLOS Computational Biology},
  keywords     = {Modelling and Simulation, Genetics, Molecular Biology, Antibiotics, Drug interactions},
  publisher    = {Public Library of Science},
  title        = {{Minimal biophysical model of combined antibiotic action}},
  doi          = {10.1371/journal.pcbi.1008529},
  volume       = {17},
  year         = {2021},
}

@article{7569,
  abstract     = {Genes differ in the frequency at which they are expressed and in the form of regulation used to control their activity. In particular, positive or negative regulation can lead to activation of a gene in response to an external signal. Previous works proposed that the form of regulation of a gene correlates with its frequency of usage: positive regulation when the gene is frequently expressed and negative regulation when infrequently expressed. Such network design means that, in the absence of their regulators, the genes are found in their least required activity state, hence regulatory intervention is often necessary. Due to the multitude of genes and regulators, spurious binding and unbinding events, called “crosstalk”, could occur. To determine how the form of regulation affects the global crosstalk in the network, we used a mathematical model that includes multiple regulators and multiple target genes. We found that crosstalk depends non-monotonically on the availability of regulators. Our analysis showed that excess use of regulation entailed by the formerly suggested network design caused high crosstalk levels in a large part of the parameter space. We therefore considered the opposite ‘idle’ design, where the default unregulated state of genes is their frequently required activity state. We found, that ‘idle’ design minimized the use of regulation and thus minimized crosstalk. In addition, we estimated global crosstalk of S. cerevisiae using transcription factors binding data. We demonstrated that even partial network data could suffice to estimate its global crosstalk, suggesting its applicability to additional organisms. We found that S. cerevisiae estimated crosstalk is lower than that of a random network, suggesting that natural selection reduces crosstalk. In summary, our study highlights a new type of protein production cost which is typically overlooked: that of regulatory interference caused by the presence of excess regulators in the cell. It demonstrates the importance of whole-network descriptions, which could show effects missed by single-gene models.},
  author       = {Grah, Rok and Friedlander, Tamar},
  issn         = {1553-7358},
  journal      = {PLOS Computational Biology},
  number       = {2},
  publisher    = {Public Library of Science},
  title        = {{The relation between crosstalk and gene regulation form revisited}},
  doi          = {10.1371/journal.pcbi.1007642},
  volume       = {16},
  year         = {2020},
}

@article{8013,
  author       = {Currin, Christopher B. and Khoza, Phumlani N. and Antrobus, Alexander D. and Latham, Peter E. and Vogels, Tim P and Raimondo, Joseph V.},
  issn         = {1553-7358},
  journal      = {PLOS Computational Biology},
  number       = {7},
  publisher    = {Public Library of Science},
  title        = {{Think: Theory for Africa}},
  doi          = {10.1371/journal.pcbi.1007049},
  volume       = {15},
  year         = {2019},
}

@article{7103,
  abstract     = {Origin and functions of intermittent transitions among sleep stages, including short awakenings and arousals, constitute a challenge to the current homeostatic framework for sleep regulation, focusing on factors modulating sleep over large time scales. Here we propose that the complex micro-architecture characterizing the sleep-wake cycle results from an underlying non-equilibrium critical dynamics, bridging collective behaviors across spatio-temporal scales. We investigate θ and δ wave dynamics in control rats and in rats with lesions of sleep-promoting neurons in the parafacial zone. We demonstrate that intermittent bursts in θ and δ rhythms exhibit a complex temporal organization, with long-range power-law correlations and a robust duality of power law (θ-bursts, active phase) and exponential-like (δ-bursts, quiescent phase) duration distributions, typical features of non-equilibrium systems self-organizing at criticality. Crucially, such temporal organization relates to anti-correlated coupling between θ- and δ-bursts, and is independent of the dominant physiologic state and lesions, a solid indication of a basic principle in sleep dynamics.},
  author       = {Wang, Jilin W. J. L. and Lombardi, Fabrizio and Zhang, Xiyun and Anaclet, Christelle and Ivanov, Plamen Ch.},
  issn         = {1553-7358},
  journal      = {PLoS Computational Biology},
  number       = {11},
  publisher    = {Public Library of Science},
  title        = {{Non-equilibrium critical dynamics of bursts in θ and δ rhythms as fundamental characteristic of sleep and wake micro-architecture}},
  doi          = {10.1371/journal.pcbi.1007268},
  volume       = {15},
  year         = {2019},
}