Biology subjects

Reynolds, P.

Publications and source records attributed to Reynolds, P..

7 recordsLinked to original sources

bioRxiv2026

Virtual reality exposes fine-scale alterations in behaviour following loss of the ADHD-linked gene adgrl3.1 in zebrafish

Zebrafish have been used a prominent model for high-throughput phenotypic screens of candidate risk gene mutations for several disorders. This also includes models for attention deficit/hyperactivity disorder (ADHD). Traditional behavioural tests, such as the forced light/dark assay, concentrate on basic locomotion measures. However, recently developed visually-driven locomotion assays, for example closed-loop systems using virtual reality, have allowed extraction of richer data on animal locomotion and decision-making under different sensory stimuli. Here, we have used such a system to assess the behaviour in adgrl3.1 mutant fish, an established model for ADHD. Our results show that mutants exhibit a higher baseline excitability and a lower threshold for initiating motor events, demonstrating that collecting behavioural responses in an interactive environment enables a more precise characterisation of ADHD-relevant phenotypes associated with adgrl3.1 disruption. More generally, we establish a scalable translational platform to screen gene-function relationships and possible therapeutic interventions, not only for ADHD but multiple neurodevelopmental disorders.

neuroscience↗

bioRxiv2025

Early visual experience elicits cellular and functional plasticity in the retina and alters behaviour

Our interaction with the surrounding environment shapes how our brain processes sensory information and drives adaptive behaviour. This plasticity allows the brain to rewire in response to specific sensory experiences. For instance, early manipulation of visual inputs profoundly impacts brain plasticity, which is crucial for functions like size perception, object recognition, and visuospatial processing. While neuronal plasticity has been detected in visual target structures such as the colliculus, thalamus, and cortex, it remains unclear if the retina, the primary sensory organ, undergoes significant plasticity. Here, we show that the zebrafish retina demonstrates pronounced plastic transformations in response to alterations of the visual environment during development, which ultimately modifies the detection of oriented visual stimuli. We demonstrate that orientation-selective amacrine cells undergo profound morphological changes in animals exposed to distinct visual environments during development. We further find that the functional orientation-selective output from the retina is altered in a manner consistent with the visual environment in which the animals are raised and that these changes are persistent. Finally, animals tested in a virtual reality system show that early exposure to different visual environments changes their innate preference for specifically oriented patterns. Our findings unveil a unique developmental form of sensory organ plasticity with continuing structural and functional consequences.

neuroscience↗

bioRxiv2021

Establishing CREATE: Lessons learned in setting up a training environment for early-career researchers in respiratory medicine

BackgroundThe purpose of the National Health and Medical Research Council Centre of Research Excellence in Pulmonary Fibrosis (CRE-PF) is to improve and extend the lives of patients living with pulmonary fibrosis through the development of a comprehensive and integrated program of basic and clinical research and education across Australia. A key objective of the CRE-PF was establishment of a unique national training scheme, CREATE, for early-career researchers (ECRs) in respiratory research. CREATE ECRs are broadly drawn from two main fields of researchers: clinicians and scientists, where clinicians tend to be involved in part-time translational research and scientists are involved in broad scientific research including laboratory or genetic research, health economics or population research. MethodsWe describe the CREATE Program which, with limited budget and the assistance of key organisations, has provided funding opportunities (scholarships, fellowships, prizes, travel and collaboration grants), professional development (mentoring program, symposia, presentation opportunities and on-line training) and fostered a connected, supportive research community for respiratory ECRs. ResultsThe CREATE program has successfully fostered the development of the supported researchers, contributing substantially to the future of pulmonary fibrosis research in Australia. During the life of the program the CRE-PF has offered 10 PhD scholarships and five postdoctoral fellowships, awarded 13 travel grants and three grants to promote collaboration between ECRs from different institutes. A mentoring program has been established and CREATE Symposia have been held in association with key meetings. During COVID-19 restrictions, a series of virtual research meetings has offered 12 CREATE ECRs from seven universities the opportunity to present their research to a national audience. CREATE research-related achievements are impressive, including over 80 first-author publications by ECRs, and many conference presentations. Contributions to the research community, measured by committee membership, is also strong. ConclusionsIn spite of a very limited budget, wide geographic distribution of participants and the multi-disciplinary nature of the cohort, we have succeeded in providing a unique, supportive academic development environment for CREATE ECRs. Lessons learned in the process of developing this program include the importance of leveraging funding, being flexible, building networks and seeking and responding to ECR input.

scientific communication and education↗

bioRxiv2019

The ARRIVE guidelines 2019: updated guidelines for reporting animal research

Reproducible science requires transparent reporting. The ARRIVE guidelines were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour, and reproduce the methods and results. Despite considerable levels of endorsement by funders and journals over the years, adherence to the guidelines has been inconsistent, and the anticipated improvements in the quality of reporting in animal research publications have not been achieved.\n\nHere we introduce ARRIVE 2019. The guidelines have been updated and information reorganised to facilitate their use in practice. We used a Delphi exercise to prioritise the items and split the guidelines into two sets, the ARRIVE Essential 10, which constitute the minimum requirement, and the Recommended Set, which describes the research context. This division facilitates improved reporting of animal research by supporting a stepwise approach to implementation. This helps journal editors and reviewers to verify that the most important items are being reported in manuscripts. We have also developed the accompanying Explanation and Elaboration document that serves 1) to explain the rationale behind each item in the guidelines, 2) to clarify key concepts and 3) to provide illustrative examples. We aim through these changes to help ensure that researchers, reviewers and journal editors are better equipped to improve the rigour and transparency of the scientific process and thus reproducibility.

scientific communication and education↗

bioRxiv2019

Reporting animal research: Explanation and Elaboration for the ARRIVE guidelines 2019

Improving the reproducibility of biomedical research is a major challenge. Transparent and accurate reporting are vital to this process; it allows readers to assess the reliability of the findings, and repeat or build upon the work of other researchers. The NC3Rs developed the ARRIVE guidelines in 2010 to help authors and journals identify the minimum information necessary to report in publications describing in vivo experiments.\n\nDespite widespread endorsement by the scientific community, the impact of the ARRIVE guidelines on the transparency of reporting in animal research publications has been limited. We have revised the ARRIVE guidelines to update them and facilitate their use in practice. The revised guidelines are published alongside this paper. This Explanation and Elaboration document was developed as part of the revision. It provides further information about each of the 21 items in ARRIVE 2019, including the rationale and supporting evidence for their inclusion in the guidelines, elaboration of details to report, and examples of good reporting from the published literature.

scientific communication and education↗

bioRxiv2019

Customizable, engineered substrates for rapid screening of cellular cues

Biophysical cues robustly direct cell responses and are thus important tools for in vitro and translational biomedical applications. High throughput platforms exploring substrates with varying physical properties are therefore valuable, however, currently existing platforms are limited in throughput, the biomaterials used, the capability to segregate between different cues and the assessment of dynamic cellular responses. Here we present a multiwell array (3x8) using a substrate engineered with patterns that present topography or rigidity cues welded to a bottomless plate with a 96-well format. Both the patterns on the engineered substrate and the well plate format can be easily customized, permitting systematic and efficient screening of biophysical cues. Here, we demonstrate three multiwell arrays patterned with a variety of topographical and mechanical cues (nano-grooves, soft pillars and nano pillars) tested with three different cell types. Using the multiwell array, we were able to measure cell functionality using analytical modalities such as live microscopy, qPCR and fluorescent immunochemistry. Cardiomyocytes cultured on 5{micro}m grooves showed less variation in electrophysiology and contractile function. Nanopillars with 127 nm height, 100 nm diameter and 300 nm pitch showed improved chondrogenic maintenance from matrix deposition and chondrogenic gene expression. High aspect ratio pillars with an elastic shear modulus of 16 kPa mimicking the cortical bone altered cell adhesion, morphology, and increased expression of osteogenic genes. We have demonstrated the bespoke, controlled and high-throughput properties of the multiwell array that are currently unparalleled in the field today.

bioengineering↗

bioRxiv2019

Nanotopography reveals metabolites that maintain the immunosuppressive phenotype of mesenchymal stem cells

Mesenchymal stem cells (MSCs) are multipotent stem cells that are immunosuppressive and thus of considerable therapeutic potential in transplant operations. However, MSCs rapidly differentiate once in culture, making their large-scale expansion for use in immunosuppressive therapies challenging. Although the differentiation mechanisms of MSCs have been extensively investigated using materials, little is known about how materials can modulate paracrine activities of MSCs. Here, we show for the first time that nanotopography can control the immunomodulatory capacity of MSCs through decreased intracellular tension increasing oxidative glycolysis. We also use the nanotopography to identify bioactive metabolites that modulate intracellular tension, growth and immunomodulatory phenotype of MSCs in standard culture. Our findings show a novel route to support large-scale expansion of functional MSCs for therapeutic purposes

bioengineering↗