A coupled mechano-biochemical model for cell polarity guided anisotropic root growth

Plants develop new organs to adjust their bodies to dynamic changes in the environment. How independent organs achieve anisotropic shapes and polarities is poorly understood. To address this question, we constructed a mechano-biochemical model for Arabidopsis root meristem growth that integrates biologically plausible principles. Computer model simulations demonstrate how differential growth of neighboring tissues results in the initial symmetry-breaking leading to anisotropic root growth. Furthermore, the root growth feeds back on a polar transport network of the growth regulator auxin. Model, predictions are in close agreement with in vivo patterns of anisotropic growth, auxin distribution, and cell polarity, as well as several root phenotypes caused by chemical, mechanical, or genetic perturbations. Our study demonstrates that the combination of tissue mechanics and polar auxin transport organizes anisotropic root growth and cell polarities during organ outgrowth. Therefore, a mobile auxin signal transported through immobile cells drives polarity and growth mechanics to coordinate complex organ development.

A subcellular biochemical model for T6SS dynamics reveals winning competitive strategies

The Type VI secretion system (T6SS) is a broadly distributed interbacterial weapon that can be used to eliminate competing bacterial populations. Although unarmed target populations are typically used to study T6SS function, bacteria most likely encounter other T6SS-armed competitors in nature. The outcome of such battles is not well understood, neither is the connection between the outcomes with the subcellular details of the T6SS. Here, we incorporated new biological data derived from natural competitors of Vibrio fischeri light organ symbionts to build a biochemical model for T6SS function at the single cell level. The model accounts for activation of structure formation, structure assembly, and deployment. By developing an integrated agent-based model (IABM) that incorporates strain-specific T6SS parameters, we replicated outcomes of biological competitions, validating our approach. We used the IABM to isolate and manipulate strain-specific physiological differences between competitors, in a way that is not possible using biological samples, to identify winning strategies for T6SS-armed populations. We found that a tipping point exists where the cost of building more T6SS weapons outweighs their protective ability. Furthermore, we found that competitions between a T6SS-armed population and a unarmed target had different outcomes dependent on the geometry of the battlefield: target cells survived at the edges of a range expansion scenario where unlimited territory could be claimed, while competitions within a confined space, much like the light organ crypts where natural V. fischeri compete, resulted in the rapid elimination of the unarmed competitor.

Emergence of a geometric pattern of cell fates from tissue-scale mechanics in the Drosophila eye

Pattern formation of biological structures involves the arrangement of different types of cells in an ordered spatial configuration. In this study, we investigate the mechanism of patterning the Drosophila eye into a precise triangular grid of photoreceptor clusters called ommatidia. Previous studies had led to a long-standing biochemical model whereby a reaction-diffusion process is templated by recently formed ommatidia to propagate a molecular prepattern across the eye epithelium. Here, we find that the templating mechanism is instead, mechanical in origin; newly born columns of ommatidia serve as a template to spatially pattern cell flows that move the cells in the epithelium into position to form each new column of ommatidia. Cell flow is generated by a pressure gradient that is caused by a narrow zone of cell dilation precisely positioned behind the growing wavefront of ommatidia. The newly formed lattice grid of ommatidia cells are immobile, deflecting and focusing the flow of other cells. Thus, the self-organization of a regular pattern of cell fates in an epithelium is mechanically driven.

scanMiR: a biochemically-based toolkit for versatile and efficient microRNA target prediction

Despite the importance of microRNAs (miRNAs) in regulating a broad variety of biological processes, accurately predicting the transcripts they repress remains a challenge. Recent research suggests improved miRNA target prediction using a biochemical model combined with empirically-derived affinity predictions across 12mer sequences. Here, we translate this approach into a generally applicable, flexible and user-friendly tool (scanMiR). By compressing and handling miRNA 12mer affinity predictions into lightweight models, scanMiR can efficiently scan for both canonical and non-canonical binding sites on transcripts and custom sequences (including circRNAs and lncRNAs). Aggregation of binding sites into predicted transcript repression using a generalized biochemical model correlates better with experimental data than the most accurate alternative publicly available predictions. Moreover, a flexible 3'-supplementary alignment enables scanMiR to highlight and visualize unconventional modes of miRNA target mRNA interactions, such as bindings leading to target-directed miRNA degradation (TDMD) and slicing. By specifically scanning for these unconventional binding sites in brain-derived expression data, we provide a first systematic overview of potential TDMD and slicing sites on brain-specific lncRNAs as well as circRNAs. Finally, in addition to the main bioconductor package implementing these functions, we provide a user-friendly web application enabling the scanning of sequences, the visualization of predicted bindings, and the browsing of predicted target repression.

NO● Represses the Oxygenation of Arachidonoyl PE by 15LOX/PEBP1: Mechanism and Role in Ferroptosis

We recently discovered an anti-ferroptotic mechanism inherent to M1 macrophages whereby high levels of NO● suppressed ferroptosis via inhibition of hydroperoxy-eicosatetraenoyl-phosphatidylethanolamine (HpETE-PE) production by 15-lipoxygenase (15LOX) complexed with PE-binding protein 1 (PEBP1). However, the mechanism of NO● interference with 15LOX/PEBP1 activity remained unclear. Here, we use a biochemical model of recombinant 15LOX-2 complexed with PEBP1, LC-MS redox lipidomics, and structure-based modeling and simulations to uncover the mechanism through which NO● suppresses ETE-PE oxidation. Our study reveals that O2 and NO● use the same entry pores and channels connecting to 15LOX-2 catalytic site, resulting in a competition for the catalytic site. We identified residues that direct O2 and NO● to the catalytic site, as well as those stabilizing the esterified ETE-PE phospholipid tail. The functional significance of these residues is supported by in silico saturation mutagenesis. We detected nitrosylated PE species in a biochemical system consisting of 15LOX-2/PEBP1 and NO● donor and in RAW264.7 M2 macrophages treated with ferroptosis-inducer RSL3 in the presence of NO●, in further support of the ability of NO● to diffuse to, and react at, the 15LOX-2 catalytic site. The results provide first insights into the molecular mechanism of repression of the ferroptotic Hp-ETE-PE production by NO●.

Resolving leaf level metabolism of C4Setaria viridis acclimated to low light through a biochemical model

When C4 plants are exposed to low light, CO2 concentration in the bundle sheath (BS) decreases, causing an increase in photorespiration, leakiness (the ratio of CO2 leak rate out of the BS over the rate of supply via C4 acid decarboxylation), and a consequent reduction in biochemical efficiency. This can to some extent be mitigated by complex acclimation syndromes, which are of primary importance for crop productivity, but not well studied. We unveil a strategy of leaf-level low light acclimation involving regulation of electron transport processes. Firstly, we characterise anatomy, gas-exchange and electron transport of Setaria viridis grown under low light. Through a newly developed biochemical model we resolve the photon fluxes, and reaction rates to explain how these concerted acclimation strategies sustain photosynthetic efficiency. Smaller BS in low light-grown plants limited leakiness but sacrificed light harvesting and ATP production. To counter ATP shortage and maintain high assimilation rates, plants facilitated light penetration through mesophyll and upregulated cyclic electron flow in the BS. This novel shade tolerance mechanism based on optimisation of light reactions is more efficient than the known mechanisms involving the rearrangement of dark reactions and can potentially lead to innovative strategies for crop improvement.