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Biology subjects

Welch, T.

Publications and source records attributed to Welch, T..

4 recordsLinked to original sources

A general mathematical framework for modelling subnetworks of the nuclear auxin pathway

Auxins are a family of plant hormones involved in various processes across plant tissues and species. The Nuclear Auxin Pathway (NAP) consists of interacting transcription factors (ARFs) and repressors (Aux/IAAs), which govern an individual cell's response to changes in auxin concentration. These components are present in all land plants, and many species possess multiple copies of each signalling component. We present a general framework for ODE-based models of NAP submodules with the flexibility to model the promotion and repression of target genes by any combination of transcriptional regulators. We analyse published data and show that auxin treatment in Arabidopsis thaliana roots triggers a range of characteristically distinct temporal response profiles-for both target genes and the signalling components themselves. Using our modelling framework, we recapitulate aspects of this behaviour by presenting examples of real and theoretical NAP subnetworks, and by analysing the effect that these network dynamics have on auxin-mediated transcriptional responses. This work demonstrates the utility of our modelling framework as a general-purpose tool for understanding the function of certain protein-protein and protein-DNA interactions through their effects on the NAP. This exploration of the rich dynamics of more complex signalling pathways promises to advance our understanding of the NAP.

plant biology↗

Whole brain mapping of spinal-projecting neurons in larval zebrafish

To elicit voluntary movements and integrative reflexes underlying behavior, the brain sends command signals to the spinal cord via specialized long-range descending neurons, known as spinal-projecting neurons (SPNs). The vast and widespread distribution of SPNs, combined with their complex long-distance connectivity, poses a significant challenge for mapping their anatomical organization and associating specific populations with distinct functions. Here we took advantage of the transparency and genetic accessibility of larval zebrafish to uncover the fundamental principles of SPN anatomical organization in a Teleost. Using an optical backfilling method relying on photoactivable GFP, we generate a whole-brain map of all neurons sending axons towards the spinal cord. This approach reveals far more SPNs than previously described through conventional strategies, offering an unparalleled opportunity to revisit distinct spinal-projecting nuclei distributed across hindbrain, midbrain, and diencephalic structures. Combining information on cell location, morphology, and projection patterns, we propose tentative homological designations for zebrafish of SPN nuclei based on established descriptions in mammals and other vertebrates.

neuroscience↗

Temperature and predation alter metabolic scaling without changing size-based structure community in freshwater macroinvertebrates

Body size is a key trait that influences ecological processes such as metabolism, abundance, and species interactions. While the metabolic theory of ecology (MTE) proposes a universal scaling of metabolic rate with body mass, recent evidence shows that this relationship is not fixed. Environmental factors like temperature and predation can alter the metabolic scaling exponent, potentially reshaping size distribution. However, most research has examined these patterns within individual species, leaving open questions about how environmental drivers affect scaling at the community level. To address this, we performed a mesocosm experiment manipulating both temperature and fish predator presence in freshwater macroinvertebrate communities. We found that metabolic scaling at the community level is highly responsive to environmental context: warming steepened the scaling exponent in predator-free tanks but flattened it when predators were present. This suggests that larger individuals reduce their baseline metabolic rates under predation risk, especially at higher temperatures. Interestingly, the slope of the community size distribution remained stable across treatments, indicating that shifts in metabolic scaling occurred independently of changes in size structure. Together, these findings highlight the environmental sensitivity of metabolic scaling and suggest that links between metabolism scaling and size distribution may be more complex than MTE predicts.

ecology↗

A Binary RNA and DNA Self-Amplifying Platform for Next Generation Vaccines and Therapeutics

Conventional mRNA-based vaccines were instrumental in lowering the burden of the pandemic on healthcare systems and in reducing mortality. However, such first-generation vaccines have significant weaknesses. Here, we describe a high-performance binary recombinant vectoral platform offering the flexibility to be used as a self-amplifying mRNA or a self-amplifying DNA. Both formats drive long-lasting expression and actuate robust antibody responses against SAR-CoV-2 spike, and neither format require encapsulation with lipid nanoparticles (LNP) in the generation immune responses. The platform combines the power of conventional mRNA with the low-dosage of self-amplifying vectors together with the simplicity, rapid creation, ease of storage, and convenience of distribution of plasmid DNA vectors. This platform promises to pave the way for more effective, less expensive, and truly democratized vaccines and therapeutics. One-Sentence SummaryGemini: a versatile platform that improves on existing vaccine formats in terms of effectiveness, manufacturing, distribution, and cost.

immunology↗