Biology subjects

Meir, Y.

Publications and source records attributed to Meir, Y..

8 recordsLinked to original sources

bioRxiv2026

A minimal kinase-phosphatase system and its lipid substrates self-organize into dynamic patterns

Competing lipid kinases and phosphatases are critical for organizing cellular membranes, but whether a minimal system can autonomously organize proteins and lipids into dynamic spatiotemporal patterns is unknown. Here, we report the in vitro reconstitution of the Legionella phosphatidylinositol (PI) 3-kinase MavQ and PI 3-phosphatase SidP. Together with their lipid substrates, PI and PI 3-phosphate (PI3P), these enzymes form a minimal self-organizing system that generates ATP-dependent spatiotemporal patterns, including traveling waves, on model membranes. These behaviors arise from MavQs cooperative membrane binding, SidPs phosphatase activity, and the continual interconversion and redistribution of PI and PI3P within a conserved membrane pool. A reaction-diffusion model reproduces the observed dynamics and predicts that lipid conservation prevents patterns from propagating across membrane discontinuities, which we verify experimentally. Together, these findings establish enzymatic modification of membrane lipids as a distinct molecular strategy for biological pattern formation.

biophysics↗

bioRxiv2024

Bacterial defense and phage counter-defense lead to coexistence in a modeled ecosystem

Bacteria have evolved many defenses against invading viruses (phage). Typically, each bacterium carries several defense systems, while each phage may carry multiple counter-defense systems. Despite the many bacterial defenses and phage counter-defenses, in most environments, bacteria and phage coexist, with neither driving the other to extinction. How is coexistence realized in the context of the bacteria/phage arms race, and how are the sizes of the bacterial immune and phage counter-immune repertoires determined in conditions of coexistence? Here we develop a simple mathematical model to consider the evolutionary and ecological dynamics of competing bacteria and phage with different immune/counter-immune repertoires. An analysis of our model reveals an ecologically stable fixed point exhibiting coexistence. This fixed point agrees with the experimental observation that each individual bacterium typically carries multiple defense systems, though fewer than the maximum number possible. However, in simulations, the populations typically remain dynamic, exhibiting chaotic fluctuations around this fixed point. We obtain quantitative predictions for the mean, amplitude, and timescale of these dynamics. Our results provide a framework for understanding the evolutionary and ecological dynamics of the bacteria/phage arms race, and demonstrate how bacteria/phage coexistence can stably arise from the coevolution of bacterial defense systems and phage counter-defense systems.

microbiology↗

bioRxiv2022

Lytic and temperate phage naturally coexist in a dynamic population model

Obligate lytic and temperate phage preying on the same bacteria coexist despite the presumption that a single resource should only support a single competitor. We construct a mathematical model demonstrating that such coexistence is a natural outcome of chaotic dynamics arising from competition among multiple phage and their lysogens. While obligate lytic (virulent) phage populations typically dominate, surprisingly, they also more readily fluctuate to extinction within a local community.

ecology↗

bioRxiv2021

piRNAs of Caenorhabditis elegans broadly silence nonself sequences through functionally random targeting

Small non-coding RNAs such as piRNAs serve as guides for Argonaute proteins, enabling sequence-specific, post-transcriptional regulation of gene expression. The piRNAs of Caenorhabditis elegans have been observed to bind targets with high mismatch tolerance, and appear to lack specific transposon targets, unlike piRNAs in Drosophila melanogaster and other organisms. These observations support a model in which C. elegans piRNAs provide a broad, indiscriminate net of silencing, acting in competition with siRNAs associated with the CSR-1 Argonaute that specifically protect self genes from silencing. However, the breadth of piRNA targeting has not been subject to in-depth quantitative analysis, nor has it been explained how piRNAs are distributed across sequence space to achieve complete coverage. Through a bioinformatic analysis of piRNA sequences, incorporating an original metric of piRNA-target distance, we demonstrate that C. elegans piRNAs are functionally random, in that their coverage of sequence space is comparable to that of random sequences. By possessing a sufficient number of distinct, essentially random piRNAs, C. elegans is able to target arbitrary nonself sequences with high probability. This result elucidates the mechanism by which newly transcribed mRNAs in C. elegans are classified as self or nonself, and has implications for piRNA evolution and biogenesis.

bioinformatics↗

bioRxiv2020

Mechanical frustration of phase separation in the cell nucleus by chromatin

Liquid-liquid phase separation is a fundamental mechanism underlying subcellular organization. Motivated by the striking observation that optogenetically-generated droplets in the nucleus display suppressed coarsening dynamics, we study the impact of chromatin mechanics on droplet phase separation. We combine theory and simulation to show that crosslinked chromatin can mechanically suppress droplets coalescence and ripening, as well as quantitatively control their number, size, and placement. Our results highlight the role of the subcellular mechanical environment on condensate regulation.

biophysics↗

bioRxiv2020

Sequence dependence of biomolecular phase separation

Cells are home to a wide variety of biomolecular condensates - phase-separated droplets that lack a membrane. In addition to nonspecific interactions, phase separation depends on specific binding motifs between constituent molecules. Nevertheless, few rules have been established on how these specific, heterotypic interactions drive phase separation. Using lattice-polymer simulations and mean-field theory, we show that the sequence of binding motifs strongly affects a polymers ability to phase separate, influencing both phase boundaries and condensate properties (e.g. viscosity and polymer diffusion). We find that sequences with large blocks of a single motif typically form more inter-polymer bonds which promote phase separation. Notably, the sequence of binding motifs influences phase separation primarily by determining the conformational entropy of self-bonding by single polymers. This contrasts with systems where the molecular architecture primarily affects the energy of the dense phase, providing a new entropy-based mechanism for the biological control of phase separation.

biophysics↗

bioRxiv2020

Decoding the physical principles of two-component biomolecular phase separation

Cells possess a multiplicity of non-membrane bound compartments, which form via liquid-liquid phase separation. These condensates assemble and dissolve as needed to enable central cellular functions. One important class of condensates is those composed of two associating polymer species that form one-to-one specific bonds. What are the physical principles that underlie phase separation in such systems? To address this question, we employed coarse-grained molecular dynamics simulations to examine how the phase boundaries depend on polymer valence, stoichiometry, and binding strength. We discovered a striking phenomenon - for sufficiently strong binding, phase separation is suppressed at rational polymer stoichiometries, which we termed the magic-ratio effect. We further developed an analytical dimer-gel theory that confirmed the magic-ratio effect and disentangled the individual roles of polymer properties in shaping the phase diagram. Our work provides new insights into the factors controlling the phase diagrams of biomolecular condensates, with implications for natural and synthetic systems.

biophysics↗

bioRxiv2018

Concerted 2-5A-Mediated mRNA Decay and Transcription Reprogram Protein Synthesis in dsRNA Response

RNA degradation by RNase L during 2-5A-mediated decay (2-5AMD) is a conserved mammalian stress response to viral and endogenous double-stranded RNA (dsRNA). 2-5AMD onsets rapidly and facilitates a switch of protein synthesis from homeostasis to production of interferons (IFNs). To understand the mechanism of this protein synthesis reprogramming, we examined 2-5AMD in human cells. 2-5AMD triggers polysome collapse characteristic of a translation initiation defect, but translation initiation complexes and ribosomes purified from the translation-arrested cells remain functional. Using spike-in RNA-seq we found that basal messenger RNAs (mRNAs) rapidly decay, while mRNAs encoding IFNs and IFN-stimulated genes evade 2-5AMD and accumulate. The IFN evasion results from the combined effect of better mRNA stability and positive feedback amplification in the IFN response. Therefore, 2-5AMD and transcription act in concert to revamp the cellular mRNA composition. The resulting preferential accumulation of innate immune mRNAs establishes \"prioritized\" synthesis of defense proteins.

cell biology↗