Biology subjects

Morgan, J. M.

Publications and source records attributed to Morgan, J. M..

3 recordsLinked to original sources

bioRxiv2026

A Large Animal Model of Heritable Pulmonary Arterial Hypertension UsingGene-edited BMPR2 Sheep

Pulmonary Arterial Hypertension (PAH) is a rare vascular disorder characterized by elevated pressure in pulmonary arteries, eventually leading to right ventricular failure. Approximately 50% of pediatric disease and 20% of adult disease can be linked to a genetic mutation, with nearly 70% of these cases involving mutations in the bone morphogenetic protein receptor type 2 (BMPR2) locus. Investigations using rodent models have made significant advances in our understanding of BMPR2 signaling; however, limited data exist regarding the onset and course of PAH, and etiologies for phenotypic expression in these patients remain unknown. In this work, we describe the development of a novel ovine model of heritable PAH. Because homozygous disruption of BMPR2 is embryonic lethal, we developed heterozygous BMPR2 sheep by using a PAM-disrupting synonymous single stranded oligodeoxyribonucleotide alongside a single guide RNA and Cas9 mediated gene editing strategy. The resulting BMPR2(+/-) lambs demonstrated cardiac and pulmonary vascular pathology that are consistent with BMPR2 mutation-driven PAH observed in humans. Given the genetic and physiological similarities of BMPR2(+/-)sheep to humans with heritable PAH, this large animal model will serve as a vital platform for mechanistic molecular studies and will provide a much-needed pre-clinical model for extensive treatment evaluations.

molecular biology↗

bioRxiv2024

A Neural Network Model of Visual Attention Integrating Biased Competition and Reinforcement Learning

We present a Recurrent Vision Transformer (Recurrent ViT) that integrates a capacity-limited spatial memory module with self-attention to emulate primate-like visual attention. Trained via reinforcement learning on a spatially cued orientation-change detection task, our model exhibits hallmark behavioral signatures of primate attention--including improved detection accuracy and faster reaction times for cued stimuli that scale with cue validity. Analysis of its self-attention maps reveals rich temporal dynamics: spatial biases induced by cues are maintained during blank intervals and reactivated prior to anticipated stimulus changes, mirroring the top-down modulation observed in primate studies. Moreover, targeted manipulations of internal attention weights yield performance changes analogous to those produced by microstimulation in attentional control regions such as the frontal eye fields and superior colliculus. These findings demonstrate that embedding recurrent, memory-driven mechanisms within transformer architectures may provide a computational framework for linking artificial and biological attention

neuroscience↗

bioRxiv2021

T-cell microvilli simulations show operation near packing limit and impact on antigen recognition.

T-cells are immune cells that continuously scan for foreign-derived antigens on the surfaces of nearly all cells, termed antigen presenting cells (APCs). They do this by dynamically extending numerous protrusions called microvilli (MV) that contain T-cell receptors (TCRs) towards the APC surface in order to scan for antigens. The number, size, and dynamics of these MV, and the complex multi-scale topography that results, play a yet unknown role in antigen recognition. We develop an anatomically informed model of the T-cell/APC interface to elucidate the role of MV dynamics in antigen sensitivity and discrimination. We find that MV surveillance reduces antigen sensitivity compared to a completely flat interface unless MV are stabilized in an antigen-dependent manner and find that MV have only a modest impact on antigen discrimination. The model highlights that MV contacts optimise the competing demands of fast scanning speeds of the APC surface with antigen sensitivity and that T-cells operate their MV near the interface packing limit. Finally, we find that observed MV contact lifetimes can be largely influenced by conditions in the T-cell/APC interface with these lifetimes often being longer than the simulation or experimental observation period. The work highlights the role of MV in antigen recognition. Significance StatementT-cells search for foreign-derived antigens on the surface of antigen presenting cells (APC) by dynamically extending tubular protrusions called microvilli (MV) which form membrane close-contacts. Although known for decades, their role in antigen recognition remains unclear. Guided by recent experiments, we built an anatomically informed stochastic model of MV scanning and compared with a topologically flat interface. We find that MV scanning modestly impacts antigen discrimination, yet it enables T-cells to balance the competing effects of maintaining sensitivity while conducting rapid APC surveillance. The model can reconcile discrepancies in observed MV lifetimes and demonstrates that observed area coverage fractions correspond to geometric packing limits. Our work suggests that MVs promote positive signaling outcomes despite anatomical constraints to close contact formation.

biophysics↗