Biology subjects

Dobson, A.

Publications and source records attributed to Dobson, A..

7 recordsLinked to original sources

bioRxiv2023

Orthogonal axes of microbiome variation associated with functionally distinct transcriptomic signatures in the gut of wild Drosophila melanogaster

Gut microbiota are fundamental for healthy animal function, but the evidence that host function can be predicted from microbiota taxonomy remains equivocal, and natural populations remain understudied compared to laboratory animals. Paired analyses of covariation in microbiota and host parameters are powerful approaches to characterise host-microbiome relationships mechanistically, especially in wild populations of animals that are also lab models, enabling insight into the ecological basis of host function at a molecular and cellular level. The fruitfly Drosophila melanogaster is a preeminent model organism, amenable to field investigation byomic analyses. Here we present an analysis of wild male D. melanogaster, with paired measurements of (A) bacterial diversity and abundance, measured by 16S amplicon sequencing; and (B) the host gut transcriptome. We found orthogonal axes of microbial genera, which correspond to differential expression of host genes. The differentially-expressed gene sets were enriched in functions including protein translation, mitochondrial respiration, immunity and reproduction. Each gene set had a distinct functional signature, suggesting that wild flies exhibit a range of distinct axes of functional variation, which correspond to orthogonal axes of microbiome variation. These findings strengthen the bridge between the wild ecology and functional genetics of a leading host-microbiome model.

ecology↗

bioRxiv2022

The importance of reaction norms in dietary restriction and ageing research

Ageing research has progressed rapidly through our ability to modulate the ageing process. Pharmacological and dietary treatments can increase lifespan and have been instrumental in our understanding of the mechanisms of ageing. Recently, several studies have reported genetic variance in response to these anti-ageing interventions, questioning their universal application and making a case for personalised medicine in our field. As an extension of these findings the response to dietary restriction was found to not be repeatable when the same genetic mouse lines were retested. We show here that this effect is more widespread with the response to dietary restriction also showing low repeatability across genetic lines in the fly (Drosophila melanogaster). We further argue that variation in reaction norms, the relationship between dose and response, can explain such conflicting findings in our field. We simulate genetic variance in reaction norms and show that such variation can: 1) lead to over- or under-estimation of treatment responses, 2) dampen the response measured if a genetically heterogeneous population is studied, and 3) illustrate that genotype-by-dose-by-environment interactions can lead to low repeatability of DR and potentially other anti-ageing interventions. We suggest that putting experimental biology and personalised geroscience in a reaction norm framework will aid progress in ageing research.

genetics↗

bioRxiv2022

Natural helminth infections reduce relative abundance of inflammation-inducing Prevotella in wild primates

Microbes living within the mammalian gastrointestinal tract affect the metabolization and extraction of dietary nutrients, immune function, colonization by pathogens, and risk of autoimmune disease. While most microbiome studies focus on sequences of the 16S gene shared by Bacteria and Archaea, these are not the only regular inhabitants of mammalian guts. Macroparasites such as helminths are nearly ubiquitous in wildlife, and a quarter of the worlds human population harbors helminths; these worms affect host physiology as they compete with microbiota over host resources while also affecting host immunity, and changing the host microbiome. Little is understood about how helminths interact with microbiomes to affect host disease states, and few studies have examined these interactions in natural systems in genetically diverse hosts experiencing coinfections and other stressors. We surveyed the microbiomes and helminth parasites of wild primates and found strong associations between helminths and microbes in the bacterial microbiome. Notably, we find that the presence of a strongyle we hypothesize to be hookworm is correlated strongly with decreased relative abundance of Prevotella species, a lineage associated with inflammatory bowel disease humans. This observed decline in Prevotella relative abundance, a genus implicated in several host autoimmune and inflammatory disorders, motivates future research on whether the mixed results of helminthic therapy (i.e., "infecting" patients with gastrointestinal nematodes to treat various diseases) stem from the mixed causes of inflammation, and whether inflammation specifically correlated with Prevotella-driven dysbiosis can be mediated through mechanisms mimicking how hookworms and other nematodes behave in the gastrointestinal ecosystem of their hosts. Our findings lend ground-truthed support to previous lab-based studies and limited/restricted human trials showing potential benefits, via microbial modulation, of nematode therapy in treating inflammatory bowel disease. Our study adds statistical weight to a link between helminths and a specific lineage of microbes associated with inflammation.

ecology↗

bioRxiv2021

Mito-nuclear variation in transgenerational and reproductive effects of amino acid and lipid nutrition

Epistasis between mitochondrial and nuclear genomes can modulate fitness effects of nutrition. Are these "mitonuclear" effects deterministic with regard to optimal nutrition? Which nutrients and genetic loci participate? Here, in fruitflies, we show that mitonuclear epistasis repeatably dictates fitness effects of dietary lipids and amino acids, with a tripartite interaction emerging as an unprecedented source of quantitative variation. We also observed diet-dependent developmental lethality and parental effects, but only in specific mitonucleotypes. Associating phenotype to mtDNA variation implicated a non-coding RNA (mt:lrRNA), suggesting a novel mechanism, with epistasis between mitochondria-derived regulatory factors and the nuclear genome producing qualitative differences in how diet impacts fitness. SUMMARYCombined action of nuclear genotype and regulatory loci on mtDNA produces major differences in fitness impacts of nutrition.

genetics↗

bioRxiv2020

Species and intra-specific competition affect growth in greenhouse more than mycorrhizal colonization on Quercus rubra and Acer rubrum seedlings

AimsDistributions of mycorrhizal guilds correlate with differences in soil nutrient availability and tend to predominate ecosystems where plant growth and development are limited by either soil phosphorus (AM, arbuscular mycorrhiza) or nitrogen (EM, ectomycorrhiza) (Read, 1991). In an effort to characterize functional trait differences, we designed a common garden greenhouse experiment to measure growth and colonization responses between two tree seedling species (Acer rubrum and Quercus rubra) that associate with the two major mycorrhizal guilds. MethodsIn a fully factorial, 12-week greenhouse common garden experiment, seedlings were treated to three levels of nitrogen and phosphorus availability, and grown under inter- and intra-species competition. Change in heights and stem diameters were tracked and mycorrhizal colonization was quantified by percent of total and morphology. ResultsRelative growth rates were higher for Acer rubrum seedlings across treatments and intra-species competition had a strong negative effect on height and stem diameter, especially for Quercus rubra. Both species were highly colonized (>50%) by typically endomycorrhizal forms (arbuscules and vesicles) but varied in the distribution of morphological forms present in cells. ConclusionsThis study highlights the plasticity of tree seedling symbiosis during early developmental stages and challenges the strict static categorization of plant species associations with particular mycorrhizal guilds.

ecology↗

bioRxiv2018

A family of transcription factors that limit lifespan: ETS factors have conserved roles in longevity

Increasing average population age, and the accompanying burden of ill health, is one of the public health crises of our time. Understanding the basic biology of the ageing process may help ameliorate the pathologies that characterise old age. Ageing can be modulated, often through changes in gene expression where regulation of transcription plays a pivotal role. Activities of Forkhead transcription factors (TFs) are known to extend lifespan, but detailed knowledge of the broader transcriptional networks that promote longevity is lacking. This study focuses on the E twenty-six (ETS) family of TFs. This family of TFs is large, conserved across metazoa, and known to play roles in development and cancer, but the role of its members in ageing has not been studied extensively. In Drosophila, an ETS transcriptional repressor, Aop, and an ETS transcriptional activator, Pnt, are known to genetically interact with Foxo and activating Aop is sufficient to extend lifespan. Here, it is shown that Aop and Foxo effect a related gene-expression programme. Additionally, Aop can modulate Foxos transcriptional output to moderate or synergise with Foxo activity depending on promoter context, both in vitro and in vivo. In vivo genome-wide mRNA expression analysis in response to Aop, Pnt or Foxo indicated, and further experiments confirmed, that combinatorial activities of the three TFs dictate metabolic status, and that direct reduction of Pnt activity is sufficient to promote longevity. The role of ETS factors in longevity was not limited to Pnt and Aop. Knockdown of Ets21c or Eip74EF in distinct cell types also extended lifespan, revealing that lifespan is limited by transcription from the ETS binding site in multiple cellular contexts. Reducing the activity of the C. elegans ETS TF Lin-1 also extended lifespan, a finding that corroborates established evidence of roles of this TF family in ageing. Altogether, these results reveal the ETS family of TFs as pervasive and evolutionarily conserved brokers of longevity.

genetics↗

bioRxiv2018

Critical transitions in malaria transmission models are consistently generated by superinfection

The history of infectious disease modelling essentially begins with the papers by Ross on malaria [1-5]. These models assume that the dynamics of malaria can most simply be characterized by two equations that describe the prevalence of malaria in the human and mosquito hosts. This structure has formed the central core of models for malaria and most other vector-borne diseases for the last century with occasional additions acknowledging important aetiological details. We partially add to this tradition by describing a malaria model that provides for vital dynamics in the vector and the possibility of super-infection in the human host; reinfection of asymptomatic hosts before they have cleared a prior infection. These key features of malaria aetiology create the potential for break points in the prevalence of infected hosts, sudden transitions that seem to characterize malarias response to control in different locations. We show that this potential for critical transitions is a general and underappreciated feature of any model for vector borne diseases with incomplete immunity and asymptomatic patients, including the canonical Ross-McDonald model. Ignoring these details of the hosts immune response to infection can potentially lead to serious misunderstanding in the interpretation of malaria distribution patterns and the design of control schemes for other vector-borne diseases.

epidemiology↗