Biology subjects

Sgro, A. E.

Publications and source records attributed to Sgro, A. E..

5 recordsLinked to original sources

bioRxiv2026

Memory from variability: Heritable short-term cellular memory emerges from stochastic biochemical reaction networks

Cells exhibit a mysterious form of selective heritable short-term memory, influencing outcomes as diverse as cell fate decisions in embryos and environmental responses in cancer cells and bacteria. Here, we present a simple theoretical framework explaining how this selective memory can arise from the reactions regulating molecular levels in cells. Our key insight is that related cells retain more similar molecular concentrations relative to random cells when a greater variance of possible concentration states is created during a single cell generation than is created by cell division across a population. This persistence of molecular similarity down a lineage constitutes a form of heritable short-term memory. We identify the biochemical networks that produce, modify, and degrade molecules as an underexplored source of these additional molecular concentration states. Using experimentally informed simulations, we find that the strength and duration of molecular similarity down a lineage depend on tunable network properties, explaining why some cellular traits persist only briefly while others last generations. These contributions to molecular concentration variance from biochemical reaction networks act in concert with gene expression and other regulatory processes to shape the protein composition of cells. Our framework yields clear, testable predictions for determining how biochemical network architectures drive non-genetic cellular inheritance.

biophysics↗

bioRxiv2022

Self-cleaving 2A peptides allow for expression of multiple genes in Dictyostelium discoideum

The social amoeba Dictyostelium discoideum is a model for a wide range of biological processes including chemotaxis, cell-cell communication, phagocytosis, and development. Interrogating these processes with modern genetic tools often requires the expression of multiple transgenes. While it is possible to transfect multiple transcriptional units, the use of separate promoters and terminators for each gene leads to large plasmid sizes and possible interference between units. In other eukaryotic systems this challenge has been addressed through polycistronic expression mediated by 2A viral peptides, permitting efficient, co-regulated gene expression. Here, we screen the most commonly used 2A peptides, porcine teschovirus-1 2A (P2A), Thosea asigna virus 2A (T2A), equine rhinitis A virus 2A (E2A), and foot-and-mouth disease virus 2A (F2A), for activity in D. discoideum. We find that these 2A sequences are effective but that, unexpectedly, combining the coding sequences of two proteins into a single transcript leads to notable decreases in expression level with strain-dependent magnitudes, suggesting unexplored constraints of gene expression in D. discoideum that merit further investigation. Our results show that P2A is the optimal sequence for polycistronic expression, opening up new possibilities for genetic engineering in this model system.

molecular biology↗

bioRxiv2021

Robust coordination of collective oscillatory signaling requires single-cell excitability and fold-change detection

Complex multicellular behaviors are coordinated at the level of biochemical signaling networks, yet how this decentralized mechanism enables robust control in variable environments and over many orders of magnitude of spatiotemporal scales remains an open question. A stunning example of these behaviors is found in the microbe Dictyostelium discoideum, which uses the small molecule cyclic AMP (cAMP) to drive the propagation of collective signaling oscillations leading to multicellular development. The critical design features of the Dictyostelium signaling network remain unclear despite decades of mathematical modeling and experimental interrogation because each model makes different assumptions about the network architecture and in general, normalizing models for direct comparison presents a major challenge. We overcome this challenge by using recent experimental data to normalize the time and response scales of five major signal relay network models to one another and assess their ability to recapitulate experimentally-observed population and single-cell dynamics. We find that to successfully reproduce the full range of observed dynamical behaviors, single cells must be excitable and respond to the relative fold-change of environmental signals. This suggests these features represent robust principles for coordinating cellular populations through oscillatory signaling and that single-cell excitable dynamics are a generalizable route for controlling population behaviors.

systems biology↗

bioRxiv2021

Ventral Stress Fibers Induce Plasma Membrane Deformation in Human Fibroblasts

Interactions between the actin cytoskeleton and the plasma membrane are essential for many eukaryotic cellular processes. During these processes, actin fibers deform the cell membrane outward by applying forces parallel to the fibers major axis (as in migration) or they deform the membrane inward by applying forces perpendicular to the fibers major axis (as during cytokinesis). Here we describe a novel actin-membrane interaction in human dermal myofibroblasts. When labeled with a cytosolic fluorophore, the myofibroblasts developed prominent fluorescent structures on the ventral side of the cell. These structures are present in the cell membrane and colocalize with ventral actin stress fibers, suggesting that the fibers bend the membrane to form a "cytosolic pocket" for the fluorophores to flow into, creating the observed structures. The existence of this pocket was confirmed by transmission electron microscopy. Dissolving the stress fibers, inhibiting fiber protein binding, or inhibiting myosin II binding of actin removed the observed structures. However, decreasing cellular contractility did not remove the structures. Taken together, our results illustrate a novel actin-membrane bending topology where the membrane is deformed outwards rather than being pinched inwards, resembling the topological inverse of cytokinesis.

cell biology↗

bioRxiv2018

Eco-evolutionary significance of ‘loners’

Loners, individuals out-of-sync with a coordinated majority, occur frequently in nature. Are loners incidental byproducts of large-scale synchronization attempts or are they part of a mosaic of life-history strategies? Here, we provide the first empirical evidence of naturally occurring heritable variation in loner behavior, using the social amoeba Dictyostelium discoideum. Moreover, we show that Dictyostelium loners--cells that do not join the multicellular life-stage-- result from a dynamic population-partitioning process. Underlying this partitioning, we find evidence that each cell makes a stochastic, signal-based decision resulting in an imperfectly synchronized multicellular development affected by both abiotic (environmental porosity) and biotic (strain-specific signaling) factors. Finally, we predict that when strains differing in their partitioning behavior co-occur, cross-signaling impacts slime-mold diversity across spatio-temporal scales. Loners are therefore critical to understanding collective and social behaviors, multicellular development, and ecological dynamics in D. discoideum. More broadly, across taxa, imperfect synchronization might be adaptive by enabling diversification of life-history strategies.

ecology↗