Biology subjects

Graham, J. M.

Publications and source records attributed to Graham, J. M..

5 recordsLinked to original sources

bioRxiv2026

Pervasive effects of Wolbachia on host body mass and metabolic rate

Metabolic rate is a widely variable trait that reflects organismal energy expenditure. At least half of all arthropod species carry maternally transmitted Wolbachia bacteria, but it is poorly understood how these endosymbionts affect host physiology and fitness. We tested how two central host traits, body mass and standard metabolic rate (SMR), are altered by Wolbachia for nine diverse Drosophila fly species and 13 co-occurring Wolbachia variants diverged roughly 150 million years. Interspecific trait variation was structured according to the host phylogeny, but within each host system, Wolbachia almost always altered body mass and/or SMR. Wolbachia often caused increases or decreases in body mass that, in some cases, also led to mass-dependent effects on whole-organism SMR. Other Wolbachia altered mass-adjusted SMR. These variable effects are plausibly explained by complex interactions among Wolbachia and host genomes, as documented for other traits (e.g., Wolbachia-induced cytoplasmic incompatibility). Endosymbiont effects on body mass and metabolic rate likely have cascading consequences for host biology and evolution, because these central traits are correlated with many aspects of host physiology, behavior, and life history. This also applies to hosts transinfected with Wolbachia from Drosophila to reduce the impacts of pathogens and pests on multiple continents.

evolutionary biology↗

bioRxiv2026

Self-organizing physical and biochemical interactions explain diverse behaviours in Physarum polycephalum

How can simple organisms lacking nervous systems encode and transmit environmental signals to generate complex, adaptive behaviours? Using the unicellular organism Physarum polycephalum as a model, we identify a unifying mechanochemical mechanism that links intracellular calcium oscillations to large-scale behavioural coordination. We first demonstrate experimentally that local perturbation of the actomyosin cortex is sufficient to induce symmetry breaking and directed migration, even in the absence of nutrient cues. Building on evidence linking calcium concentration to actin depolymerization and contractile relaxation, we develop a mechanochemical tubule model in which self-sustained calcium oscillations are coupled to pressure-driven mechanics. We show that environmental cues, encoded through the local modulation of these oscillations, give rise to directed transport and the redistribution of biomass. By extending this framework to a two-dimensional phase-field model, we demonstrate that this mechanism is sufficient to generate a diverse set of slime mould behaviours, including chemotaxis, network formation, and balancing exploration-exploitation trade-offs. In doing so, we provide a single mechanistic framework linking intracellular dynamics to organism-scale behaviour across spatial and temporal scales. Our work shows that these sophisticated behaviours can emerge from the modulation of self-sustained oscillations coupled by diffusion, providing a physically grounded mechanism for information processing in non-neural organisms and offering insight into the evolutionary origins of coordinated behaviour.

biophysics↗

bioRxiv2025

The contributions of host population size and maternal transmission rate to fluctuating Wolbachia frequencies

Many insects and other animals host heritable endosymbionts that alter host fitness and reproduction. The prevalence of facultative endosymbionts can fluctuate in host populations across time and geography for reasons that are poorly understood. This is particularly true for maternally transmitted Wolbachia bacteria, which infect roughly half of all insect species. For instance, the frequencies of several wMel-like Wolbachia, including wMel in host Drosophila melanogaster, fluctuate over time in certain host populations, but the specific conditions that generate temporal variation in Wolbachia prevalence are unresolved. We implemented a discrete generation model in the new R package symbiontmodeler to evaluate how finite-population stochasticity contributes to Wolbachia fluctuations over time in simulated host populations under a variety of conditions. Using empirical estimates from natural Wolbachia-Drosophila systems, we explored how stochasticity is determined by a broad range of factors, including host population size, maternal transmission rates, and Wolbachia effects on host fitness (modeled as fecundity) and reproduction (cytoplasmic incompatibility; CI). While stochasticity generally increases when host fitness benefits and CI are relaxed, we found that a decline in the maternal transmission rate had the strongest relative impact on increasing the size of fluctuations. We infer that non- or weak-CI-causing strains like wMel, which often show evidence of imperfect maternal transmission, tend to generate larger stochastic fluctuations compared to strains that cause strong CI, like wRi in D. simulans. Additional factors, such as fluctuating host fitness effects, are required to explain the largest examples of temporal variation in Wolbachia. The conditions we simulate here using symbiontmodeler serve as a jumping off point for understanding drivers of temporal and spatial variation in the prevalence of Wolbachia, the most common endosymbionts found in nature.

evolutionary biology↗

bioRxiv2019

STAT3 and GR cooperate to drive basal-like triple negative breast cancer gene expression and proliferation.

Breast cancers can be divided into subtypes with different prognoses and treatment responses based on global gene expression differences. Luminal breast cancer gene expression and proliferation are driven by the transcription factors Estrogen Receptor (ER), FOXA1 and GATA3. Targeting ER is the most effective therapy for treating luminal breast cancer because ER is the master regulator of the luminal gene expression program. In contrast, it is unclear which transcription factors are responsible for driving the gene expression signature that defines basal-like triple negative breast cancer, and there are no targeted therapies approved to treat this aggressive subtype of the disease. This study utilized integrated analysis of DNA methylation, chromatin accessibility, transcription factor binding, and gene expression in large collections of breast cancer cell lines and patient tumors to identify transcription factors responsible for the basal-like gene expression program. The results of this study indicate that glucocorticoid receptor (GR) and signal transducer and activator of transcription 3 (STAT3) bind to the same genomic regulatory regions that are specifically open and unmethylated in basal-like breast cancer. These transcription factors cooperate to regulate expression of hundreds of genes in the basal-like gene expression signature and these downstream genes are associated with poor prognosis in patients. Furthermore, combination treatment with small molecule drugs that inhibit both transcription factors leads to synergistic decreases in cell proliferation in cell lines and patient-derived organoid models. This study demonstrates that GR and STAT3 cooperate to regulate the basal-like breast cancer gene expression program and provides the basis for improved therapy for basal-like triple negative breast cancer through rational combination of STAT3 and GR inhibitors.

cancer biology↗

bioRxiv2017

Optimal construction of army ant living bridges

Integrating the costs and benefits of collective behaviors is a fundamental challenge to understanding the evolution of group living. These costs and benefits can rarely be quantified simultaneously due to the complexity of the interactions within the group, or even compared to each other because of the absence of common metrics between them. The construction of living bridges by New World army ants - which they use to shorten their foraging trails - is a unique example of a collective behavior where costs and benefits have been experimentally measured and related to each other. As a result, it is possible to make quantitative predictions about when and how the behavior will be observed. In this paper, we extend a previous mathematical model of these costs and benefits into a general framework for analyzing the optimal formation, and final configuration, of army ant living bridges. We provide experimentally testable predictions of the final bridge position, as well as the optimal formation process for certain cases, for a wide range of scenarios, which more closely resemble common terrain obstacles that ants encounter in nature. As such, our framework offers a rare benchmark for determining the evolutionary pressures governing the evolution of a naturally occurring collective animal behavior.

animal behavior and cognition↗