Biology subjects

Le, T. P.

Publications and source records attributed to Le, T. P..

9 recordsLinked to original sources

bioRxiv2026

Diffusion MRI of cortical organoids reveals protocol-associated spatial reproducibility and increasing diffusivity with diffusion time

Early human cortical development involves rapid changes in cytoarchitecture that remain difficult to interrogate non-invasively. Biophysical diffusion MRI models provide a potential window onto this microstructure, including water exchange across cell membranes, but their assumptions are difficult to validate directly in developing human tissue. Human cortical organoids provide a tractable biological model in which diffusion measurements can be related to tissue architecture within the same specimen. We scanned six fixed cortical organoids at 9.4~T, three grown under a directed and three under an undirected differentiation protocol, at three diffusion times and b-values up to 7000~s/mm$^2$. Center-to-periphery profiles of DKI-derived diffusion metrics were reproducible across the directed organoids but more variable across the undirected organoids, while nuclear staining revealed greater variability in the internal architecture of the undirected organoids. Unexpectedly, mean diffusivity increased with diffusion time in more than 80% of tissue voxels in both batches, opposite to previous organoid measurements. Across 12,348 simulated two-compartment substrates, this increase was reproduced only with permeable membranes and an extracellular diffusivity substantially exceeding the apparent intracellular diffusivity, a regime that challenges assumptions commonly used in current gray-matter exchange models. These results support cortical organoids as biologically realistic platforms for probing early cortical microstructure and testing diffusion models under controlled conditions, while remaining amenable to post-MRI histological validation.

neuroscience↗

bioRxiv2026

Forecasting high pathogenicity avian influenza with a stochastic mechanistic model: performance and lessons for Australia

High pathogenicity avian influenza (HPAI) H5N1 clade 2.3.4.4b has caused a global panzootic with unprecedented impacts on wildlife and livestock, making evidence-based disease mitigation and outbreak response critical. In this paper, we describe a spatiotemporal mechanistic model of infectious disease dynamics developed for the HPAI Modelling Challenge and its implications for forecasting and policy in Australia. To emulate emergency response conditions, we adapted an existing model for rapid deployment rather than developing a bespoke model. We refined the model iteratively across the challenge to better analyse the provided outbreak data. Throughout the challenge, we accurately forecast temporal trends and local outbreak spread, but could not predict rarer, long-distance dispersal events. The challenge ended before HPAI H5N1 was first detected in Australia (June 2026), providing a critical opportunity to test our response modelling readiness for an incursion in wildlife and potential spillover into commercial poultry. Our experience identifies three key considerations for Australia's HPAI H5N1 preparedness: targeted enhancements to our model to improve forecast precision and enable scenario-based policy evaluation; the critical value of pre-existing modelling infrastructure for rapid emergency response; and sustained collaboration between research and policy institutions to align modelling capabilities with outbreak response requirements.

bioinformatics↗

bioRxiv2025

MRS4Brain: a processing toolbox for preclinical MR spectroscopy and spectroscopic imaging data

ObjectivesMagnetic resonance spectroscopy is a non-invasive technique for probing metabolism and underpins advanced methods such as magnetic resonance spectroscopic imaging (MRSI) and diffusion-weighted spectroscopy (DWS). MRSI enables spatial mapping of metabolite distributions, offering insights into regional metabolic heterogeneity that single-voxel spectroscopy (SVS) cannot capture. However, MRSI produces large multidimensional datasets and requires complex processing pipelines, limiting reproducibility and accessibility. While human studies benefit from advanced processing tools, similar developments in preclinical research remain scarce, highlighting a demand for practical tools accessible to non-experts. MethodsTo address this need, we introduce the MRS4Brain Toolbox, a freely available MATLAB-based platform for preclinical spectroscopy, including MRSI, SVS, and DWS. ResultsThe toolbox integrates reconstruction, preprocessing, quantification, quality control, brain segmentation automatically overlaid on metabolite maps, modeling, and statistical analysis into unified workflows accessible via a graphical interface. ConclusionBy streamlining data processing and reducing technical barriers, MRS4Brain Toolbox promotes reproducibility, harmonization, and broader adoption of advanced spectroscopic techniques in preclinical studies, ultimately facilitating translational research.

neuroscience↗

bioRxiv2025

Estimating the impact of invasive pests and diseases on ecosystem services: modelling carbon sequestration loss due to myrtle rust (Austropuccinia psidii exotic strains) in Australia

The impacts of invasive pests and diseases are routinely estimated and measured in the context of agriculture, but less so in the context of biodiversity and ecosystem services. In this study, we estimate the potential reduction of carbon sequestration in Australia due to exotic strains of myrtle rust (Austropuccinia psidii, also known as Puccinia psidii, guava rust, or [o]hia rust). We model the contribution of susceptible plants to carbon sequestration and use previously known myrtle rust damage estimates to susceptible plant species and the valuation of carbon sequestration in Australia to estimate the potential monetary impact. This method can be systematically extended to other pests impacting plant growth as well as other ecosystem services. In the case of myrtle rust, we estimate that it could cause up to a 1.6% (95% CI: 1.3-2.0%) annual reduction in national carbon sequestration if it were to spread across all climatically suitable areas in Australia, resulting in an estimated value loss of over $340 million AUD (over $220 million USD) per year. Compared with contemporary syntheses of known cost estimates, our results show that the potential consequences of invasive species can be substantially larger than reported, and may be currently undervalued. Our work shows the need to systematically compile the potential impacts and costs to the environment and ecosystem services globally, to support both biosecurity decision-making and climate-change related initiatives such as net-zero emissions targets and reforestation efforts.

ecology↗

bioRxiv2024

Is testing the bee-all and end-all of varroa eradication?

Varroa destructor is a significant European honeybee pest, impacting agricultural industries globally. Since arriving in 2022, Australia faces the possibility that varroa will become established in European honeybee colonies nationally. Australia initially pursued a strategy of testing and subsequently eliminating hives infested with varroa. These management efforts raise interesting questions about the interplay between hive testing and elimination, and the spread of varroa between hives. This study uses mathematical modelling to investigate how combined hive testing and elimination strategies impact the spread of varroa through a network of European honeybee hives. We develop a model of both within-hive reproduction of varroa and hive testing, and between-hive movement of varroa on a network of hives. This model is used to assess the impact of various testing and hive elimination strategies on the total number of hives eliminated on the network of hives. Each model simulation starts with a single infested hive, and from this we observed one of two dynamics: either the infestation is caught before spreading, or varroa spreads extensively through the network before being caught by testing. Within our model we implement two common hive testing methods - sugar shake and alcohol testing. A shared limitation of these testing methods is that they can only detect mites in a specific stage of their lifecycle. As such, testing is not only dependent on how many varroa mites are in a hive, but what lifecycle stage the mites are in at the time of testing. By varying testing and movement parameters, we see that this testing limitation greatly impacts the number of hives eliminated in various scenarios. We find that there are largely two invasion possibilities: either there is only a small incursion, or that varroa achieves complete spread on the network. Furthermore, testing earlier, or testing more frequently, does not guarantee a smaller invasion. Our model results suggest irregular testing schedules, e.g. testing multiple times in close succession rather than just once in a given timeframe, may help overcome the limitations of common hive testing strategies.

ecology↗

bioRxiv2023

Coordination of cell cycle and morphogenesis during organ formation

Organ formation requires precise regulation of cell cycle and morphogenetic events. Using the Drosophila embryonic salivary gland (SG) as a model, we uncover the role of the SP1/KLF transcription factor Huckebein (Hkb) in coordinating cell cycle regulation and morphogenesis. The hkb mutant SG exhibits defects in invagination positioning and organ size due to abnormal death of SG cells. Normal SG development involves distal-to-proximal progression of endoreplication (endocycle), whereas hkb mutant SG cells undergo abnormal cell division, leading to cell death. Hkb represses the expression of key cell cycle and pro-apoptotic genes in the SG. Knockdown of cyclin E or cyclin-dependent kinase 1, or overexpression of fizzy-related rescues most of the morphogenetic defects observed in the hkb mutant SG. These results indicate that Hkb plays a critical role in controlling endoreplication by regulating the transcription of key cell cycle effectors to ensure proper organ formation.

developmental biology↗

bioRxiv2022

Multifunctional role of GPCR signaling in epithelial tube formation

Epithelial tube formation requires Rho1-dependent actomyosin contractility to generate the cellular forces that drive cell shape changes and rearrangement. Rho1 signaling is activated by G protein-coupled receptor (GPCR) signaling at the cell surface. During Drosophila embryonic salivary gland (SG) invagination, the GPCR ligand Folded gastrulation (Fog) activates Rho1 signaling to drive apical constriction. The SG receptor that transduces the Fog signal into Rho1-dependent myosin activation has not been identified. Here, we reveal that the Smog GPCR transduces Fog signal to regulate Rho kinase accumulation and myosin activation in the medioapical region of cells to control apical constriction during SG invagination. We also report on unexpected Fog-independent roles for Smog in maintaining epithelial integrity and organizing cortical actin. Our data supports a model wherein Smog regulates distinct myosin pools and actin cytoskeleton in a ligand-dependent manner during epithelial tube formation.

developmental biology↗

bioRxiv2020

Isoform-specific roles of the Drosophila filamin-type protein Jitterbug (Jbug) during development

Filamins are highly conserved actin-crosslinking proteins that regulate organization of the actin cytoskeleton. As key components of versatile signaling scaffolds, filamins are implicated in developmental anomalies and cancer. Multiple isoforms of filamins exist, raising the possibility of distinct functions for each isoform during development and in disease. Here, we provide an initial characterization of jitterbug (jbug), which encodes one of the two filamin-type proteins in Drosophila. We generate Jbug antiserum that recognizes all of the spliced forms and reveals differential expression of different Jbug isoforms during development, and a significant maternal contribution of Jbug protein. To reveal the function of Jbug isoforms, we create new genetic tools, including a null allele that deletes all isoforms, hypomorphic alleles that affect only a subset, and UAS lines for Gal4-driven expression of the major isoforms. Using these tools, we demonstrate that Jbug is required for viability and that specific isoforms are required in the formation of actin-rich protrusions including thoracic bristles in adults and ventral denticles in the embryo. We also show that specific isoforms of Jbug show differential localization within epithelia and that maternal and zygotic loss of jbug disrupts Crumbs (Crb) localization in several epithelial cell types.

developmental biology↗

bioRxiv2019

Microtubule-dependent protein trafficking promotes apical constriction during tissue invagination

The formation of an epithelial tube is a fundamental process for organogenesis. During Drosophila embryonic salivary gland (SG) invagination, Folded gastrulation (Fog)- dependent Rho-associated kinase (Rok) promotes contractile apical myosin formation to drive apical constriction. Microtubules (MTs) are also crucial for this process and are required for forming and maintaining apicomedial myosin. However, the underlying mechanism that coordinates actomyosin and MT networks still remains elusive. Here, we show that MT-dependent intracellular trafficking regulates apical constriction during SG invagination. Key components involved in protein trafficking, such as Rab11 and Nuclear fallout (Nuf), are apically enriched near the SG invagination pit in a MT-dependent manner. Disruption of the MT networks or knockdown of Rab11 impairs apicomedial myosin formation and apical constriction. We show that MTs and Rab11 are required for apical enrichment of the Fog ligand and the continuous distribution of the apical determinant protein Crumbs (Crb) and the key adherens junction protein E-Cadherin (E-Cad) along junctions. Targeted knockdown of crb or E-Cad in the SG disrupts apical myosin networks and results in apical constriction defects. Our data suggest a role of MT- and Rab11-dependent intracellular trafficking in regulating actomyosin networks and cell junctions, to coordinate cell behaviors during tubular organ formation.

developmental biology↗