Biology subjects

Denton, J. A.

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

7 recordsLinked to original sources

bioRxiv2022

Ecological Drivers of Community Cohesion

From protocellular to societal, networks of living systems are complex and multi-scale. The assembly of these intricate interdependencies, under ecological pressures, can be nearly impossible to understand using pairwise methods. We develop a mathematical and computational model based on a four-strain Saccharomyces cerevisiae synthetic inter-dependent system. Our system leverages transiently structured ecologies for achieving community cohesion. We show how ecological interventions could reverse or slow the extinction rate of a cohesive community. An interconnected system first needs to persist long enough to be a subject of natural selection. Our emulation of Darwins warm little ponds with an ecology governed by transient compartmentalisation provides the necessary persistence. Our results find utility across scales of organisation, stressing the importance of cyclic processes in major evolutionary transitions engineering of synthetic microbial consortia and conservation biology.

ecology↗

bioRxiv2021

Suppressed eusocial reproduction supports evolutionary convergence over co-option

Eusociality represents a major evolutionary transition that arose independently in at least 12 insect lineages. Despite this prevalence, there remains considerable uncertainty surrounding the catalysing event and underlying genomic changes that enable such modifications. Commonly associated with this evolutionary transition is establishing and maintaining the reproductive division of labour (e.g. a reproductive queen and no-reproductive workers). This division is, at least in part, induced and maintained by highly species-specific pheromones. However, genomic analysis remains conflicted on the role of pheromones in this evolutionary transition. Specifically, if there was co-option of a common pheromone-sensitive genetic pathway present in all progenitor species or strong lineage-specific selection converging on similar transcriptomic signatures. Using a solitary insect model, we sought to determine if various species-specific pheromones induced similar transcriptomic responses, thus activating similar pathways. We measured the transcriptomic and physiological response of a solitary insect, Drosophila melanogaster, to pheromones from bumblebees, honey bees, and termites. Each treatment induced the same strong physiological response - a decreased ovary size. However, employing several methods of transcriptomic analysis, we did not observe conservation in pheromone-mediated gene/pathway regulation. Thus, despite a conserved phenotypic response, the underpinning transcriptome was vastly different. This suggests that pheromone-mediated eusociality is the result of convergent evolution. We propose that mechanisms maintaining eusociality (i.e. proto-pheromone) in early stages of eusocial evolution in each group, thus, acting as a primer for eusociality. This early state is then refined through strong selective pressure, resulting in a converging eusocial phenotype. Visual Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=144 SRC="FIGDIR/small/451940v3_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@117ad33org.highwire.dtl.DTLVardef@16bf4f5org.highwire.dtl.DTLVardef@9f215aorg.highwire.dtl.DTLVardef@146c0f5_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1.C_FLOATNO C_FIG

evolutionary biology↗

bioRxiv2021

UNIGEMS: plasmids and parts to facilitate teaching on assembly, gene expression control and logic in E. coli

Synthetic biology is as an excellent vehicle for education, as it enables creative combination of engineering and molecular biology approaches for quantitative characterisations of the assembled constructs. However, there is a limited number of resources available for such applications in the educational context, where straightforward setup, easily measurable phenotypes and extensibility are of particular importance. To expand the availability of education-friendly resources to teach synthetic biology and genetic engineering, we developed Unigems, a set of 10 plasmids that enable out-of-the-box investigations of principles of gene expression control, as well as more complex designs a biological logic gate. The system uses a common high-copy plasmid backbone and a common set of primers to enable Gibson-assembly of PCR-generated or synthesised parts into a target vector. It currently has two reporter genes with either two constitutive (high- or low-level) or two inducible (lactose- or arabinose-) promoters, as well as a single-plasmid implementation of an AND logic gate. The Unigems system has already been employed in undergraduate teaching settings, during outreach events and for training of iGEM teams. All plasmids have been deposited in Addgene.

synthetic biology↗

bioRxiv2021

Apis mellifera cognition as a tool for scientific engagement

In addition to the crowdsourcing of experimental data, citizen science, and scientific engagement more broadly, serve as a bridge between researchers and the wider community. This serves to foster a greater understanding of the scientific method and science-based solutions generally. Apis mellifera (honeybees) are a well-established model for the study of learning and cognition and can serve as an engaging outreach system for this wider community. Here, we developed and implemented a protocol using well established honeybee conditioning protocols to safely study the effects of caffeine and dopamine on learning performance. Using this protocol, a group of high-school aged students as part of the Ryukyu Girls program demonstrated that caffeine, but not dopamine, significantly reduced the number of trials required for a successful conditioning response. This allowed these students to explore the scientific method in a relatable and engaging way. Simple SummaryGlobal scientific literacy can be improved through widespread and effective community engagement by researchers. We propose Apis mellifera (honeybee) as an public engagement tool due to widespread awareness of colony collapse and the bees importance in food production. Moreover, their cognitive abilities make for engaging experiments. Their relative ease of cultivation means that studies can be performed cost-effectively, especially when partnering with local aperists. Using a proxy for honeybee learning, a group of non-specialist high-school-aged participants obtained data suggesting that caffeine, but not dopamine, improved learning. This hands-on experience facilitated student understanding of the scientific method, factors that shape learning and the importance of learning for hive health.

animal behavior and cognition↗

bioRxiv2020

Perturbations of Ribosomal Protein Expression Reveal Overlapping Gene Networks between Drosophila Minutes and Human Cancer

Ribosomal proteins (RPs) are critical to all cellular operations through their key roles in ribosome biogenesis and translation, as well as their extra-ribosomal functions. Leveraging previously identified RP mutants we characterised the RP macro transcriptome and sought to compare it with transcriptomes of pathologies associated with failures of ribosomal function, cancer and Zika virus (ZIKV). Single gene-based analysis revealed highly variable transcriptomes of RP mutations with little overlap in genes that were differentially expressed. In contrast, weighted gene co-expression network analysis revealed a highly conserved transcriptomic network pattern across all RP mutants studied. In addition, when we compared network changes in RP mutants, we observed similarities to transcriptome alterations in human cancer, and thus confirming the oncogenic role of RPs. Finally, it is known that ZIKV infection influences translational machinery, but this study shows infection network changes dissimilar to those of either the RP mutation or cancer.

genetics↗

bioRxiv2020

Evaluation of pigmentation gene knock-outs by CRISPR as potential targets for the genetic engineering of Culex quinquefasciatus

Culex quinquefasciatus mosquitoes are a globally widespread vector of several human and animal pathogens. Their biology and behavior allow them to thrive in proximity to urban areas, rendering them a constant public health threat. Their mixed bird/mammal feeding behavior further offers a vehicle for zoonotic pathogens transmission to people, and separately, poses a threat to the conservation of insular birds. The advent of CRISPR has led to the development of novel technologies for the genetic engineering of wild mosquito populations, yet research in Culex quinquefasciatus has been lagging compared to other disease vectors. Here we use this tool to disrupt a set of five pigmentation genes in Culex quinquefasciatus that, when altered, lead to visible, homozygous-viable phenotypes. We further validate this approach in separate laboratories and in two distinct strains of Culex quinquefasciatus that are relevant to potential future public health and bird conservation applications. We generate a double-mutant line, demonstrating the possibility of sequentially combining multiple such mutations in a single individual. Lastly, we target two loci, doublesex in the sex-determination pathway and proboscipedia a hox gene, demonstrating the flexibility of these methods applied to novel targets. Our work provides a platform of seven validated loci that could be used for targeted mutagenesis in Culex quinquefasciatus and the future development of genetic suppression strategies for this species. Furthermore, the mutant lines generated here could have widespread utility to the research community using this model organism, as they could be used as targets for transgene delivery, where a copy of the disrupted gene could be included as an easily-scored transgenesis marker.

genetics↗

bioRxiv2019

Engineering recombination between diverged yeast species reveals genetic incompatibilities

The major cause of the sterility of F1 hybrids formed between Saccharomyces cerevisiae and Saccharomyces paradoxus is anti-recombination. The failure of homologous chromosomes from the different species to recombine causes them to mis-segregate, resulting in aneuploid gametes, most of which are inviable. These effects of anti-recombination have previously impeded the search for other forms of incompatibility, such as negative genetic interactions (Bateson-Dobzhoansky-Muller incompatibilities). By suppressing the meiotic expression of MSH2 and SGS1, we could increase recombination and improve hybrid fertility seventy-fold. This allowed us to recover meiotic tetrads in which all four gametes were viable, ensuring that segregation had occurred properly to produce perfectly haploid, not aneuploid, recombinant hybrid gametes. We sequenced the genomes of 84 such tetrads, and discovered that some combinations of alleles from different species were significantly under-represented, indicating that there are incompatible genes contributing to reproductive isolation.

evolutionary biology↗