Biology subjects

Gartner, M.

Publications and source records attributed to Gartner, M..

4 recordsLinked to original sources

bioRxiv2026

Epistasis facilitates the long-term antigenic evolution of the influenza B virus hemagglutinin

The antigenic drift of viral glycoproteins must be balanced by purifying selection pressure to maintain functionality. Understanding these evolutionary processes is key to predicting and combating viral evolution but is primarily based on influenza A(H3N2), which may limit generalisability. By characterising the influenza B virus haemagglutinin (HA) over 8 decades of circulation in humans, we found continuous genetic diversification, punctuated with antigenic changes that did not follow a linear path in antigenic space. Antigenic change is primarily underpinned by re-occurring mutations and deletions at positions 136, 150, 162-165, 197 and 203. These residues form complex epistatic networks that modulate the antigenic impact of mutation recycling. They also generate permissive backbones on which immune escape can emerge with limited replicative fitness cost. Our study identifies critical similarities and differences with A(H3N2) evolution and demonstrates the role of epistasis in balancing antigenic novelty with viral fitness. Our findings and genetic, antigenic and phenotypic datasets support the development of genotype-to-phenotype prediction tools, but such predictions need to capture the complex outcomes of epistasis.

microbiology↗

bioRxiv2026

Metabolostasis failure thresholds are linked with network topology, metabolite solubility, and translational control

Cells maintain metabolite homeostasis (metabolostasis) by buffering fluctuations in metabolite levels, yet the limits of this buffering and the mechanisms underlying metabolic toxicity remain poorly understood. To study this, we systematically overfed metabolites in Saccharomyces cerevisiae and quantified associations with growth inhibition, intracellular aggregation, and multiomic perturbations. We identify metabolite-specific failure thresholds at which amyloid-like aggregates are observed, with graded growth inhibition detectable at sub-threshold concentrations, suggesting toxicity mechanisms beyond transporter saturation. Metabolites with higher network influence and broader pathway participation are associated with higher failure thresholds and smaller pathway disturbances. These patterns are associated with chemical properties and solubility: more soluble metabolites, while broadly tolerated, are associated with localised aggregates at their failure thresholds, whereas less soluble metabolites are associated with larger systemic pathway disruptions. Multiomic integration identifies a two-tiered translational regulatory architecture characterising cellular resilience to metabolic overfeeding. General resilience is associated with transcriptional commitment to resource conservation via attenuation of anabolic pathways. Metabolite-specific defense is characterised by high-magnitude translational regulatory events; for example, engagement of aromatic catabolism under phenylalanine overfeeding and energetic control pathways under glycine overfeeding. Together, our results operationally define metabolostasis as a cellular system associated with constraint of metabolite concentrations, coordination of network and pathway-level regulation, and buffering against amyloid-like aggregation, highlighting how network topology, pathway architecture, and chemical properties are associated with metabolic resilience and toxicity thresholds.

cell biology↗

bioRxiv2022

No evidence that urbanisation encourages wild red foxes (Vulpes vulpes) to exploit unfamiliar food-related objects when first discovered

Urbanisation is the fastest form of landscape transformation on the planet, but researchers understanding of the relationships between urbanisation and animal adaptability is still in its infancy. In terms of foraging, bold and innovative behaviours are proposed to help urban animals access, utilise, and exploit novel anthropogenic food sources. Red foxes (Vulpes vulpes) are one of the best known and widespread urban-dwelling species. However, despite frequent stories, images, and videos portraying them as "pests" due to their exploitation of food-related objects (e.g., raiding the contents of outdoor bins), it is unknown whether they are bolder and more innovative in terms of their likelihood of exploiting these resources compared to rural populations. In the current study, we gave novel food-related objects to foxes from 104 locations (one object per location) across a large urban-rural gradient. To access the food, foxes had to use behaviours necessary for exploiting many food-related objects in the real world (e.g., biting, pushing, pulling, or lifting human-made materials). Despite all foxes acknowledging the objects, foxes from 31 locations touched them, while foxes from 12 locations gained access to the food inside. A principal component analysis of urban and other landscape variables (e.g., road, greenspace, and human population density) revealed that urbanisation was significantly and positively related to the likelihood of foxes touching, but not exploiting, the objects. Thus, while urban foxes may be bolder than rural populations in terms of their willingness to physically touch novel food-related objects, our findings are inconsistent with the notion that they are more innovative and pose a general nuisance to people by exploiting these anthropogenic resources. HighlightsO_LIThe impact of urbanisation on animal adaptability remains unclear C_LIO_LIBold and innovative behaviour may help some urban species thrive C_LIO_LIWe studied wild red foxes responses to novel food-related objects C_LIO_LIUrban foxes were bolder, but not more innovative, than rural foxes C_LIO_LIUrbanisation may favour bolder, not more innovative, fox behaviour C_LI

animal behavior and cognition↗

bioRxiv2022

Engineered Riboswitch Nano-carriers as a Possible Disease-Modifying Treatment for Metabolic Disorders

Both DNA- and RNA-based nanotechnologies are remarkably useful for in vitro molecular-scale device engineering and are applied in a vast array of applications. However, while the function of nucleic acid nanostructures is robust under in vitro settings, their implementation in real-world conditions requires overcoming their inherent degradation sensitivity and subsequent loss of function. Viruses are minimalistic yet sophisticated supramolecular assemblies, able to protect their nucleic acid content in inhospitable biological environments. Inspired by this natural ability, we engineered RNA-virus-like particles (VLPs) nanocarriers (NCs). We showed that the VLPs can serve as an excellent protective shell against nuclease-mediated degradation. We then harnessed biological recognition elements and demonstrated how engineered riboswitch NCs can act as a possible disease-modifying treatment for genetic metabolic disorders. The functional riboswitch is capable of selectively and specifically binding metabolites and preventing their self-assembly process and its downstream effects. When applying the riboswitch nano-carriers to an in vivo yeast model of adenine accumulation and self-assembly, significant inhibition of the sensitivity to adenine feeding was observed. In addition, using an amyloid-specific dye, we proved the riboswitch nano-carriers ability to reduce the level of intracellular amyloid-like cytotoxic structures. The potential of this RNA therapeutic technology does not stop at metabolic disorders, as it can be easily fine-tuned to be applied to other conditions and diseases.

bioengineering↗