Biology subjects

Macadam, A.

Publications and source records attributed to Macadam, A..

6 recordsLinked to original sources

bioRxiv2026

Conserved transcriptomic heat stress response signatures in coral recruits selectively bred from thermally distinct broodstock in a low-differentiation system

Thermal history provenancing can guide the choice of parental broodstock for selective breeding of corals from distinct reefs and has been proposed as an intervention for enhancing climate resilience. However, the genetic and molecular mechanisms underlying resultant offspring responses to heat stress, particularly during early life stages, remain poorly understood. Here, we generated Acropora tersa larvae and recruits by crossing parental colonies from the historically warmer Martin Reef and cooler Davies Reef and assessed the effects of within- and between-reef crosses on genetic diversity and transcriptional responses to heat stress. Genome-wide single nucleotide polymorphism analyses showed that broodstock from Martin and Davies Reefs were weakly differentiated (FST = 0.008) and exhibited comparable heterozygosity, as did all larval offspring groups. Transcriptomic analyses of recruits exposed to heat stress (32 {degrees}C for 36 days) revealed that both within- and between-reef offspring groups activated conserved stress-response pathways, with seven genotype-independent heat-responsive genes detected across all offspring groups. Differential expression and enrichment analyses showed induction of defence, protein homeostasis, intracellular transport, and metabolic processes alongside repression of growth- and signalling-related functions, consistent with the Type A General Coral Stress Response. Taken together, these findings suggest that the benefits of thermal history provenancing-informed selective breeding may be limited in low-differentiation systems and that targeted pre-screening of broodstock may help capture functional genetic variation relevant to restoration applications.

genomics↗

bioRxiv2026

Enhanced survival and lower growth in assisted gene flow corals during a marine heatwave driven by local adaptation

Recent increases in the frequency of mass coral bleaching and mortality events have caused shifts in species composition and rapid global reef decline. Genetic-based techniques, like assisted gene flow (AGF), offer the potential to enhance corals climate readiness by introducing genetic variation associated with heat tolerance into vulnerable populations. This method remains untested in the wild during a marine heatwave. To this end, we selectively bred AGF corals by crossing parent Acropora tersa corals collected across five Great Barrier Reef (GBR) locations spanning a thermal and bleaching gradient. Breeding produced intra- and inter-regional offspring that were then deployed to a central GBR reef. This deployment reef was subsequently hit by a marine heatwave (>31.4{degrees}C for 17 days and >6 Degree Heating Weeks). Heat tolerance-associated traits (survival, growth, and bleaching) were compared between AGF offspring and a native control cross over the 95 days in the wild. Overall, AGF offspring had 4x greater odds of survival compared to controls, and 2x greater odds compared to northern juveniles. Growth rates were 14% higher in control juveniles compared to the mean growth rate across all AGF crosses. Interestingly, heat-stress assays (32{degrees}C) of the parental adult corals showed similar patterns to their offspring, with higher survival and lower bleaching of corals from warmer northern reefs. Taken together, these findings providing critical support that the selective breeding of AGF corals can provide enhanced survival under marine heatwave conditions in the wild. It also suggests further evaluation is needed for trait-specific responses to effectively match donor and recipient reefs in restoration planning.

ecology↗

bioRxiv2024

Upscaling production of immunogenic poliovirus virus-like particles in Pichia Pastoris by controlled fermentation

The success of the poliovirus (PV) vaccines has enabled the near-eradication of wild PV, however, their continued use post-eradication poses a significant threat to maintaining a polio-free world. Recombinant virus-like particles (VLPs) that lack the viral genome remove this risk. Here, we demonstrate the production of PV VLPs for all three serotypes by controlled fermentation using Pichia pastoris. We determined the cryo-EM structure of a new PV-2 mutant, termed SC5a, in comparison to PV-2 SC6b VLPs described previously and investigated the immunogenicity of PV-2 SC5a VLPs. Finally, a trivalent immunogenicity trial using bioreactor-derived VLPs of all three serotypes in the presence of Alhydrogel adjuvant, showed that these VLPs outperform the current IPV vaccine in the standard vaccine potency assay, offering the potential for dose-sparing. Overall, these results provide further evidence that yeast-produced VLPs have the potential to be a next-generation polio vaccine in a post-eradication world.

microbiology↗

bioRxiv2024

Non-lytic spread of poliovirus requires the nonstructural protein 3CD

Non-enveloped viruses like poliovirus (PV) have evolved the capacity to spread by non-lytic mechanisms. For PV, this mechanism exploits the host secretory autophagy pathway. Virions are selectively incorporated into autophagosomes, double-membrane vesicles that travel to the plasma membrane, fuse, and release single-membrane vesicles containing virions. Loading of cellular cargo into autophagosomes relies on direct or indirect interactions with microtubule-associated protein 1B-light chain 3 (LC3) that are mediated by motifs referred to as LC3-interaction regions (LIRs). We have identified a PV mutant with a severe defect in non-lytic spread. An F-to-Y substitution in a putative LIR of the nonstructural protein 3CD prevented virion incorporation into LC3-positive autophagosomes and virion trafficking to the plasma membrane for release. Using high-angle annular dark-field scanning transmission electron microscopy to monitor PV-induced autophagosome biogenesis, for the first time, we show that virus-induced autophagic signals yield normal autophagosomes, even in the absence of virions. The F-to-Y derivative of PV 3CD was unable to support normal autophagosome biogenesis. Together, these studies make a compelling case for a direct role of a viral nonstructural protein in the formation and loading of the vesicular carriers used for non-lytic spread that may depend on the proper structure, accessibility, and/or dynamics of its LIR. The studies of PV 3CD protein reported here will hopefully provoke a more deliberate look at the presence and function of LIR motifs in viral proteins of viruses known to use autophagy as the basis for non-lytic spread. IMPORTANCEPV and other enteroviruses hijack the cellular secretory autophagy pathway for non-lytic virus transmission. While much is known about the cellular factors required for non-lytic transmission, much less is known about viral factors contributing to transmission. We have discovered a PV nonstructural protein required for multiple steps of the pathway leading to vesicle-enclosed virions. This discovery should facilitate identification of the specific steps of the cellular secretory autophagy pathway and corresponding factors commandeered by the virus and may uncover novel targets for antiviral therapy.

microbiology↗

bioRxiv2021

Predicting selection-response gradients of heat tolerance in a wide-ranging reef-building coral

Ocean temperatures continue to rise due to climate change but it is unclear if heat tolerance of marine organisms will keep pace with warming. Understanding how tolerance scales from individuals to species and quantifying adaptive potentials is essential to forecasting responses to warming. We reproductively crossed corals from a globally distributed species (Acropora tenuis) on the Great Barrier Reef (Australia) from three thermally distinct reefs to create 85 offspring lineages. Individuals were experimentally exposed to temperatures (27.5, 31, and 35.5 {degrees}C) in adult and two critical early life stages (larval and settlement) to assess acquired heat tolerance via outcrossing of offspring phenotypes by comparing five physiological responses (photosynthetic yields, bleaching, necrosis, settlement, and survival). Adaptive potentials and physiological reaction norms were calculated across three stages to integrate heat tolerance at different biological scales. Selective breeding improved larval survival to heat by 1.5 - 2.5x but did not result in substantial enhancement of settlement, although population crosses were significantly different. At heat, adults were less variable compared to larval responses in warmer reefs compared to the cooler reef. Adults and offspring also differed in their mean population responses, likely underpinned by heat stress imposing strong divergent selection on adults. These results have implications for downstream selection during reproduction, evidenced by variability in a conserved heat tolerance response across offspring lineages. These results inform our ability to forecast the impacts of climate change on wild populations of corals and will aid in developing novel conservation tools like the assisted evolution of at-risk species. SUMMARY STATEMENTHeat stress exerts disruptive selection on adult corals. This likely underpins variability in offspring survival and results in differences in offspring responses to selection.

evolutionary biology↗

bioRxiv2020

Recombination in enteroviruses is a ubiquitous event independent of sequence homology and RNA structure

Genetic recombination in RNA viruses is an important evolutionary mechanism. It contributes to population diversity, host/tissue adaptation and compromises vaccine efficacy. Both the molecular mechanism and initial products of recombination are relatively poorly understood. We used an established poliovirus-based in vitro recombination assay to investigate the roles of sequence identity and RNA structure, both implicated or inferred from analysis of circulating recombinant viruses, in the process. In addition, we used next generation sequencing to investigate the early products of recombination after cellular co-infection with different poliovirus serotypes. In independent studies we find no evidence for a role for RNA identity or structure in determining recombination junctions location. Instead, genome function and fitness are of greater importance in determining the identity of recombinant progeny. These studies provide further insights into this important evolutionary mechanism and emphasise the critical nature of the selection process on a mixed virus population.

microbiology↗