Biology subjects

Harrison, P.

Publications and source records attributed to Harrison, P..

7 recordsLinked to original sources

bioRxiv2025

Salmonids reveal principles of regulatory evolution following autotetraploidization

Early vertebrate autotetraploidization events may have enabled major innovations by expanding the genetic material for functional diversification, yet their ancient timing obscures how genome doubling reshaped gene regulatory evolution. Salmonids provide a unique window to these mechanisms, because they experienced a comparatively recent autotetraploidization and are earlier in the rediploidization process - which creates new genes and regulatory elements during evolution. Here, using large-scale multiomics spanning embryonic and adult tissues in two salmonids, we investigate gene regulatory evolution following genome doubling and rediploidization, which we show is governed by developmental and tissue-specific context, with a period of maximal constraint at advanced stages of embryogenesis. This work advances understanding of vertebrate genome evolution, while providing an open resource supporting salmonid aquaculture and conservation.

evolutionary biology↗

bioRxiv2025

The influence of larval retention on coral recruitment

Marine broadcast spawners typically exhibit bipartite life-histories with distinct pelagic larvae and benthic phases. The transition between phases shapes benthic populations, but the rate of larval arrival to a reef is largely unknown due to challenges in accurately measuring supply. Once larvae arrive to a reef, reduced current flow and velocity, facilitate the transition from the water column to the benthos for inefficient swimming larvae. Yet, for coral reefs characterised by complex hydrodynamics and tides, slack current conditions typically last 1.5-3 hours and it remains unclear if such short retention periods drive significant recruitment. This study mechanistically examined the effects of water retention on the settlement of coral larvae from the water column to the benthos and subsequent longer-term recruitment over 15-months. Brief periods of slack currents (<3-hours) retained larvae in unconstrained larval supply treatments, resulting in settlement rates 40-times higher than natural, background rates. Constrained and longer retention of larvae under nets for 2.5- and 24-hours resulted in 4-7-times higher initial settlement than the unconstrained treatment and 305-times higher than background rates. However, after 15-months, similar numbers of surviving recruits were observed across all larval supply treatments, highlighting the effects of density-dependent population regulation. Observations from recruitment tiles show survival rates of coral recruits after 15-months were low (<0.25), even though gregarious settlement behaviour and settlement close to tile edges improved survival. In contrast, observations from the natural substrate show survival rates were 2.5-3.5-times higher than tiles after 15-months, indicating density-independent survival due to optimal niche space and less space limitation. Therefore, when larval supply is high and gregarious behaviour prominent, key vital rates including recruitment and mortality derived from settlement tiles are likely overestimated, as substrate and microhabitat properties between tiles and natural reef environment vary. Overall, our study highlights the prominent role of slack current conditions and local retention of larvae in facilitating the supply-to-settlement transition, and how this interacts with density-dependent processes post-settlement. Our findings underscore the need to investigate how the interaction strengths of pre-and post-settlement processes modulate early coral recovery to best model recovery trajectories for conservation and restoration prioritisation.

ecology↗

bioRxiv2025

Identifying mood instability and circadian rest-activity patterns using digital remote monitoring and actigraphy in participants at risk for bipolar disorder

Mood instability and circadian rhythm disruptions are both of increasing interest with regard to a number of psychiatric disorders, notably bipolar disorder (BD), but understanding of their nature and their interrelationship are incomplete. By definition, both have an integral temporal component and, as such, measuring them longitudinally and remotely is desirable. We conducted the Cognition and Mood Evolution across Time (COMET) study to assess the feasibility and value of digital devices to capture mood, its instability, and daily rest-activity patterns, over a 10-week period, in two groups of participants. The first group (n=37) were selected as scoring >7 on the Mood Disorder Questionnaire (MDQ) ( high MDQ), thereby having a history of mood elevation and being at risk for BD. They were compared with a group (n=37) scoring <5 on the MDQ ( low MDQ). Over a 10-week period, using a tablet, mood was rated daily, clinical ratings of depression, mania, and anxiety were captured weekly via the True Colours app, and a GENEactiv actigraph was worn to capture rest-activity pattern data. The main findings are that (1) MDQ score predicts mood instability; (2) high MDQ score is associated with more negative affect and mood symptoms than people with low MDQ, and with a different circadian activity profile; and (3) mood instability and circadian indices appear uncorrelated. The implications are that (1) remote monitoring of these domains is feasible and valuable; (2) selection of participants based on MDQ score is useful for studying mood (in)stability; and (3) the approach has potential for studies of clinical populations and for experimental medicine studies assessing interventions to reduce mood instability.

neuroscience↗

bioRxiv2024

Going with the flow: leveraging reef-scale hydrodynamics for upscaling larval-based restoration

Anthropogenic pressures are impacting coastal marine ecosystems, necessitating large-scale interventions to accelerate recovery. Propagule-based restoration holds the potential for restoring shallow coastal systems at hectare scales by harnessing natural dispersal. However, predicting propagule dispersal remains challenging due to the complex hydrodynamic nature of coastal marine ecosystems and the complex behaviours of marine propagules. To improve predictions of fine-scale larval dispersal patterns, we developed a 3D reef-scale ([~]30 m resolution) dispersal model for Lizard Island, Australia, with the aim to predict the effect of island scale hydrodynamics on the distribution of coral spawn slicks and larvae. Using in situ field observations, and dispersal simulations, we assessed the models capability to (1) forecast hydrodynamic conditions, (2) predict coral spawn slick convergence zones for collection efforts, and (3) identify optimal locations and timeframes where high particle residence time may enhance local settlement following larval delivery to damaged reefs. Predictions of convergence zones in the upper water column aligned well with field observations of coral spawn slicks. At the reef benthos, the model captured variability in current speed and direction at [~]58% of studied locations. At other locations, the model did not resolve hydrodynamic conditions due to sheltering effects and associated hydrodynamic processes occurring at a scale below 50 m. At locations where the model performed well, propagules could remain within a one-hectare area around the delivery site for 5 to 15 hours depending on locations and the timing of larval release. These high retention conditions were infrequent but occurred at least once at 15 of the 25 studied sites. Observations of local currents a posteriori confirmed model predictions, showing periods of little water movement lasting from 6.5 to 15 hours. Overall, our study highlights fine-scale dispersal modelling as a key tool for scaling up larval-based reef restoration, while also acknowledging the need for better predictions of local conditions in complex, shallow environments. Applications of fine-scale modelling, coupled with local knowledge of reproductive timing and larval behavioural ecology, assist with the mass collection of propagules upon release and in identifying areas and times of optimal larval deployment to achieve the greatest impact.

ecology↗

bioRxiv2023

Gene surgery as a potential treatment option for Nephropathic Cystinosis in vitro

Nephropathic cystinosis is a rare monogenetic kidney disease caused by mutations in the lysosomal transporter cystinosin (encoded by CTNS) that, to date, has no cure. The hallmark of this disease is lysosomal accumulation of cystine and decline in proximal tubular function leading to kidney failure early in life. In this project, we developed a novel gene repair strategy using CRISPR/Cas9 Homology-Independent Targeted Integration (HITI) to restore CTNS. A novel, non-viral peptide-mediated approach was used to deliver the Cas9-guideRNA ribonucleoprotein (RNP) complex and repair templates to conditionally immortalized proximal tubule epithelial cell (ciPTEC) lines. The repair constructs contained either mCherry (1.7 kb), the CTNS Superexon (1.7 Kb) or both (3.2 Kb). The results demonstrated that the smaller mCherry construct achieved a higher repair efficiency (63%) compared to the CTNS-mCherry construct (16%). Clonal expansion of repaired cells showed restoration of lysosomal cystine levels in 70-75% of the clones, which was accompanied by improved mitochondrial bioenergetics. In conclusion, CRISPR/Cas9 HITI can be used to precisely insert repair templates into the genome, resulting in a functional cystinosin restoration, and a reversal of the cystinotic disease phenotype.

bioengineering↗

bioRxiv2021

Selecting species for restoration in foundational assemblages

O_LIHumans have long sought to restore species, but little attention has been directed at how to best select a subset of foundation species for maintaining rich assemblages that support ecosystems, like coral reefs and rainforests that are increasingly threatened by environmental change. C_LIO_LIWe propose a two-part hedging approach that selects optimized sets of species for restoration. The first part acknowledges that biodiversity supports ecosystem functions and services, and so it takes precaution against loss by ensuring an even spread of phenotypic traits. The second part maximizes species and ecosystem persistence by weighting species based on characteristics that are known to improve ecological persistence--e.g., abundance, species range and tolerance to environmental change. C_LIO_LIUsing existing phenotypic trait and ecological characteristic data for reef building corals, we identified sets of ecologically persistent species by examining marginal returns in occupancy of phenotypic trait space. We compared optimal sets of species with those from the worlds southern-most coral reef which naturally harbors low coral diversity to show these occupy much of the trait space. Comparison with an existing coral restoration program indicated that current corals used for restoration only cover part of the desired trait space and may be improved by including species with different traits. C_LIO_LISynthesis and applications. While there are many possible criteria for selecting species for restoration, the approach proposed here addresses the need to insure against unpredictable losses of ecosystem services by focusing on a wide range of phenotypic traits and ecological characteristics. Furthermore, the flexibility of the approach enables the functional goals of restoration to vary depending on environmental context, stakeholder values, and the spatial and temporal scales at which meaningful impacts can be achieved. C_LI

ecology↗

bioRxiv2021

Analysis of Preplatelets and Their Barbell Platelet Derivatives by Imaging Flow Cytometry

Circulating large "preplatelets" undergo fission via barbell platelet intermediates into two smaller, mature platelets. In this study, we determine whether preplatelets and/or barbells are equivalent to reticulated/immature platelets by using ImageStream flow cytometry (ISFC) and super-resolution microscopy. Immature platelets, preplatelets and barbells were quantified in healthy and thrombocytopenic mice, healthy human volunteers, and patients with immune thrombocytopenia (ITP) or undergoing chemotherapy. Preplatelets and barbells were 1.9%+0.18/1.7%+0.48 (n=6) and 3.3%+1.6/0.5%+0.27 (n=12) of total platelet counts in murine and human whole blood, respectively. Both preplatelets and barbells exhibited high expression of HLA-I with high thiazole orange and mitotracker fluorescence. Tracking dye experiments confirmed that preplatelets transform into barbells and undergo fission ex vivo to increase platelet counts, with dependence upon the cytoskeleton and normal mitochondrial respiration. Samples from antibody-induced thrombocytopenia in mice and patients with ITP had increased levels of both preplatelets and barbells correlating with immature platelet levels. Furthermore, barbells were absent post-chemotherapy in patients. In mice, in vivo biotinylation confirmed that barbells, but not all large platelets, were immature. This study demonstrates that a subpopulation of large platelets are immature preplatelets that can transform into barbells and undergo fission during maturation.

cell biology↗