Search bioRxiv⌕ Search

Biology subjects

Woodling, N.

Publications and source records attributed to Woodling, N..

4 recordsLinked to original sources

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↗

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↗

Building Inclusive Leadership: A Biosciences Approach

One-size-fits-all Equity, Diversity, and Inclusion (EDI) strategies and provisioning are no longer suitable for a growing and diversifying higher education landscape; as each research discipline faces its own unique challenges to inclusion. High impact research needs reliable, decisive, and holistic approaches to leadership, but managerial and leadership skills are often considered an add-on as opposed to a necessity in modern research environments. An estimated 70% of EDI initiatives in UK Higher Education Institutions fail to flourish (Marchiondo et al. 2023) - a combinatory effect of conservative approaches to change, cultural adaptation, and departmental stability. We developed an Inclusive Leadership Programme to empower bioscientists to work autonomously and inclusively. Using a co-creation approach, the Inclusive Leadership Programme collectively defined inclusive leadership traits to create a resource. The interactive resource shares inclusive approaches to communication, feedback, recognition, and development - prioritising the experiences of those typically excluded from leadership conversations. By embedding a self-reflective scoring system, we share changes in approaches to inclusivity. After using the resource, self-perception normalises in distribution, indicating the resource provides a baseline for best practice, and space to understand personal approaches to inclusive practice in biosciences. Ultimately, the Inclusive Leadership Programme and Resource offers a template for other biological research, learning, and teaching environments to build their own tailored approach to integrating inclusivity and empowering all members to work as autonomous and inclusive leaders, regardless of seniority.

scientific communication and education↗

Sex- and strain-dependent effects of ageing on sleep and activity patterns in Drosophila

The fruit fly Drosophila is a major discovery platform in the biology of ageing due to its balance of relatively short lifespan and relatively complex physiology and behaviour. Previous studies have suggested that some important phenotypes of ageing, for instance increasingly fragmented sleep, are shared from humans to Drosophila and can be useful measures of behavioural change with age: these phenotypes therefore hold potential as readouts of healthy ageing for genetic or pharmacological interventions aimed at the underpinning biology of ageing. However, some age-related phenotypes in Drosophila show differing results among studies, leading to questions regarding the source of discrepancies among experiments. In this study, I have tested females and males from three common laboratory strains of Drosophila to determine the extent to which sex and background strain influence age-related behavioural changes in sleep and activity patterns. Surprisingly, I find that some phenotypes - including age-related changes in total activity, total sleep, and sleep fragmentation - depend strongly on sex and strain, to the extent that some phenotypes show opposing age-related changes in different sexes or strains. Conversely, I identify other phenotypes, including age-related decreases in morning and evening anticipation, that are more uniform across sexes and strains. These results reinforce the importance of controlling for background strain in both behavioural and ageing experiments, and they imply that caution should be used when drawing conclusions from studies on a single sex or strain of Drosophila. At the same time, these findings also offer suggestions for behavioural measures that merit further investigation as potentially more consistent phenotypes of ageing.

animal behavior and cognition↗