Biology subjects

Dobson, A. J.

Publications and source records attributed to Dobson, A. J..

6 recordsLinked to original sources

bioRxiv2026

AGES for Ageing: Evaluating the auxin-inducible gene expression system for use in Drosophila ageing studies

Our research is only as good as our tools allow it to be. The fruit fly Drosophila has been a fundamental discovery platform in uncovering evolutionarily conserved biological underpinnings of ageing, due in large part to an ever-expanding functional genetic toolbox which permits fine-tuneable and cell-type-specific modulation of gene expression with relative ease. However, many existing gene expression systems present limitations for studying fly ageing, including off-target effects for inducing agents that allow temporal control. More recently-generated tools such as the auxin-based gene expression system (AGES) therefore present opportunities as potential alternatives in our methodological repertoire for ageing research. Here we have evaluated the AGES system in a variety of contexts in Drosophila ageing. We find that AGES can effectively induce transgene expression across a range of ages, albeit with tissue-specific efficiency. However, we also observe several phenotypes from auxin feeding, even in non-AGES genotypes, that may confound studies focused on ageing research, including reduced body mass and reduced survival under starvation and oxidative stress conditions. We also observe phenotypes from activating the AGES machinery, including shortened lifespan, that could present challenges for using AGES in longevity-based studies. Nevertheless, we find that AGES can be used to recapitulate at least some effects of well-established pro-longevity interventions - for instance reduced fecundity from expression of a dominant-negative form of the insulin receptor - reinforcing the value of AGES in certain domains. Taken together, our results underscore the need for caution and comprehensive controls in ageing studies that rely on functional genetics, regardless of the chosen genetic toolset.

genetics↗

bioRxiv2026

Barcoding biology: Chemotype predicts variation in genotype, physiology, and stress response

Predicting biological responses to perturbations such as stress, nutrition, or pharmaceuticals could transform healthcare and biosciences. The task is challenging because complex interactions among many factors interactively drive biological variation, and thereby alter responses. However, metabolism integrates these drivers of variation, suggesting that emergent biological states may be reflected in aggregate chemical states. We define such states as chemotypes and test their predictive utility. Using Fourier-transform infrared (FTIR) spectroscopy coupled with machine learning in Drosophila melanogaster, we show that chemotypes serve as proxies for biological variation driven by sex, genotype, nutrition and age, and - critically - predict among-population variation in stress response. These findings indicate that chemotypes provide a computable and integrative representation of organismal biology, predicting genotype, phenotype, and response to perturbation.

systems biology↗

bioRxiv2025

Microbiota reduce Drosophila triacylglyceride density by providing pantothenate

Metabolism follows ground-rules that evolved in ancient bacteria: as a legacy, animal gut microbiota have abundant opportunity to modulate host metabolism, via conserved mechanisms. When these effects are beneficial, natural selection should favour hosts that reciprocally support bacterial growth. Whether microbes simply nourish hosts or more profoundly reprogram host metabolism remains to be established. Here we show that Acetobacter promote Drosophila coenzyme A, an ancient signalling metabolite, reprogramming host metabolism and generating a state that reciprocally supports bacterial growth. Impairing pathways from bacterial pantothenate to host coenzyme A increases host lipid storage, reduces nitrogen excretion, and diminishes bacterial load. These processes correspond to reprogrammed host carbohydrate handling and tissue-specific acyl-CoA pools, but live bacteria and short-chain fatty acids are dispensable. These results outline a simple microbial basis for complex host metabolic effects, via mechanisms that precede the origins of metazoa, facilitating metabolic and symbiotic homeostasis.

physiology↗

bioRxiv2025

Lifespan and fecundity impacts of reduced insulin signalling can be directed by mito-nuclear epistasis in Drosophila

The changing demography of human populations has motivated a search for interventions that promote healthy ageing, and especially for evolutionarily-conserved mechanisms that can be studied in lab systems to generate hypotheses about function in humans. Reduced Insulin/IGF signalling (IIS) is leading example, which can extend healthy lifespan in a range of animals; but whether benefits and costs of reduced IIS vary genetically within species is under-studied. This information is critical for any putative translation. Here, in Drosophila, we test for genetic variation in lifespan response to a dominant-negative form of the insulin receptor, along with a metric of fecundity to evaluate corollary fitness costs/benefits. We also partition genetic variation between DNA variants in the nucleus (nDNA) and mitochondrial DNA (mtDNA), in a fully-factorial design that allows us to assess "mito-nuclear" epistasis. We show that reduced IIS can have either beneficial or detrimental effects on lifespan, depending on the combination of mtDNA and nDNA. This suggests that, while insulin signalling has a conserved effect on ageing among species, intraspecific effects can vary genetically, and the combination of mtDNA and nDNA can act as gatekeeper.

genetics↗

bioRxiv2025

Microbiota/gut/neuron axis promotes Drosophila ageing via Acetobacter, Tachykinin, and TkR99D

Gut microbiota exert an evolutionarily conserved influence on ageing, from invertebrates to humans. How do microbes that are physically confined to the gut lumen affect the systemic physiological process of ageing? In female Drosophila, we show that microbiota increase expression of the peptide hormone Tachykinin (Tk), which corresponds to reduced lifespan. Tk is required for microbiota to shorten lifespan, with knockdown rendering flies constitutively long-lived even in the presence of an intact microbiota. This lifespan extension does not come with canonical costs to fecundity or feeding, but impacts on triacylglyceride (TAG) storage suggest adaptive functions in metabolic homeostasis. In flies with defined (gnotobiotic) microbiotas, we show that we can model Tk-dependent effects of microbiota on lifespan and TAG by monoassociation with Acetobacter pomorum. These effects require Tk in the midgut, and the cognate TK receptor TkR99D in neurons, implicating a microbiota-gut-neuron relay. This relay also appears to compromise gut barrier function in aged flies, indicating roles in healthspan as well as lifespan. However, the effect of TkR99D is independent of its reported role in insulin signalling and adipokinetic hormone signalling which, respectively, are canonical regulators of lifespan and TAG metabolism, suggesting a non-canonical role for TkR99D elsewhere in the nervous system. Altogether our results implicate a microbiota-gut-neuron axis in ageing, via a specific bacterium modulating activity of a specific and evolutionarily-conserved hormone.

genetics↗

bioRxiv2023

Outcome of Drosophila microbiota manipulation depends on dietary preservative formula and batch variation in dietary yeast

Gut microbiota are fundamentally important for healthy function in their animal hosts. The fly Drosophila melanogaster is a powerful system for understanding the underlying host/microbe interactions, with modulation of the microbiota inducing phenotypic changes that are conserved across animal taxa. The context-dependence of these responses has not been explored systematically, which may confound repeatability. Here we show that the microbiotas impact on fly triacylglyceride (TAG) levels - a commonly-measured metabolic index - depends on factors in fly media that are rarely considered or controlled, and are not standardized among laboratories: media preservative formula, yeast batch, and the interactive effect of their combinatorial variation. In studies of conventional, axenic and gnotobiotic flies, we found that microbial impacts were apparent only on specific yeast-by-preservative conditions, with TAG levels determined by a tripartite interaction of the three experimental factors. When comparing axenic and conventional flies, we found that preservatives rather than microbiota status was the main driver of variance in host TAG, and certain yeast-preservative combinations reversed microbiota effects on TAG levels. Further, comparisons between TAG levels of axenic flies and those associated with Acetobacter pomorum or Levilactobacillus brevis determined that preservatives, microbiota status, and their interaction were the major drivers of TAG variation. Our results suggest that the microbiota shapes the host TAG response in a manner dependent on the combination of the dietary factors of preservative formulation and yeast batch, with implications for repeatability, interpretation, and optimal experimental standards. ImportanceDrosophila melanogaster is a premier model for microbiome science, which has greatly enhanced our understanding of the basic biology of host-microbe biology. However, often overlooked factors such as dietary composition, including yeast batch variability and preservative formulation used, may cofound data interpretation of experiments within the same lab and lead to different findings when comparing between labs. Our study supports this concept; we find that host TAG levels are not solely dependent on the presence or absence of microbiota members, but rather the combinatorial effects of microbiota members, yeast batch, and preservative formulation used, with preservatives being the largest driver. It serves as a cautionary tale that underappreciated components of fly rearing can mask or drive phenotypes that are believed to be impacted by microbiota members.

microbiology↗