Biology subjects

Bearon, R.

Publications and source records attributed to Bearon, R..

3 recordsLinked to original sources

bioRxiv2025

Modelling Glomerular Filtration using Multispectral Optoacoustic Tomography and a Novel Near-infrared Dye

Kidney disease carries significant morbidity, mortality, and financial cost. Preclinical work exploring more accurate methods for assessing renal function is key for monitoring disease progression and the efficacy of future therapies. Measuring kidney function by dynamic contrast enhanced imaging allows us to measure left and right kidney function separately. This provides an internal control where a unilateral injury model is used. Multispectral optoacoustic tomography (MSOT) can measure the renal clearance of administered near infrared absorbers and, via the application of mathematical models, allows for the calculation of glomerular filtration rate. ABZWCY-HP{beta}CD is a cyanine dye bound to 2-hydroxylpropyl-{beta}-cyclodextrin and has shown promise as a glomerular filtration marker. Here we combine MSOT, ABZWCY-HP{beta}CD, and a modified Patlak-Rutland model to measure the glomerular filtration rate of healthy mice and following ischaemic reperfusion injury.

physiology↗

bioRxiv2021

Actin filaments act as a size-dependent diffusion barrier around centrosomes

The centrosome, a non-membranous organelle, constrains various soluble molecules locally to execute its functions. As the centrosome is surrounded by various dense components, we hypothesized that the centrosome may be bordered by a putative diffusion barrier. After quantitatively measuring the trapping kinetics of soluble proteins of varying size at centrosomes by a chemically inducible diffusion trapping assay, we found that centrosomes were highly accessible to soluble molecules with a Stokes radius of [≤] 5.1 nm, whereas larger molecules rarely reach centrosomes, indicating the existence of a size-dependent diffusion barrier at centrosomes. The permeability of barriers was tightly regulated by branched actin filaments outside of centrosomes. Such barrier gated the microtubule nucleation. We propose that actin filaments spatiotemporally constrain the distribution of molecules at centrosomes in a size-dependent manner. Significance StatementCentrosome maintains its microenvironment without membrane. Whether the dense protein complexes outside centrosomes including pericentriolar matrix, microtubules, and branched actin filaments provide physical obstruction is unclear yet. We here established a series of new tools for quantitative evaluation of the diffusion rates of varisized soluble proteins in different sub-compartments of centrosomes. Our results demonstrated that branched actin filaments, but not pericentriolar matrix or microtubules, around centrosome have acted as a size-dependent diffusion barrier and physically constrain centrosome microtubule nucleation.

cell biology↗

bioRxiv2018

4D imaging and analysis of multicellular tumour spheroid cell migration and invasion

Studying and characterising tumour cell migration is critical for understanding disease progression and for assessing drug efficacy. Whilst tumour cell migration occurs fundamentally in 3 spatial dimensions (3D), for practical reasons, most migration studies to date have performed analysis in 2D. Here we imaged live multicellular tumour spheroids with lightsheet fluorescence microscopy to determine cellular migration and invasion in 3D over time (4D). We focused on glioblastoma, which are aggressive brain tumours, where cell invasion into the surrounding normal brain remains a major clinical challenge. We developed a workflow for analysing complex 3D cell movement, taking into account migration within the spheroid as well as invasion into the surrounding matrix. This provided metrics characterising cell motion, which we used to evaluate the efficacy of chemother-apeutics on invasion. These rich datasets open avenues for further studies on drug efficacy, microenvironment composition, as well as collective cell migration and metastatic potential.

cell biology↗