Biology subjects

Shannon, M.

Publications and source records attributed to Shannon, M..

4 recordsLinked to original sources

bioRxiv2025

Replication of seizure-suppressing effects of alpha-linolenic acid on the Drosophila melanogaster paraShudderer mutant

Voltage-gated sodium channels are essential for healthy nervous system function. Mutations in voltage-gated sodium channels are associated with a range of seizure conditions. The genetics of seizure conditions are complex and often challenging to study or replicate in animal models. The Drosophila melanogaster gene paralytic (para) is the sole voltage-gated sodium channel gene in flies. The paraShudderer allele causes dominant seizure activity manifest in adult morphology and behavior. In this study we replicated previous findings of paraShudderer hyperexcitability and the ability to suppress this activity with dietary supplementation of an omega-3 fatty acid, alpha-linolenic acid (ALA). Our results support the robustness of the paraShudderer phenotype and the replicability of findings across separate lab environments.

neuroscience↗

bioRxiv2023

CD56/NCAM mediates cell migration of human NK cells by promoting integrin-mediated adhesion turnover

Natural killer (NK) cells patrol tissue to mediate lysis of virally infected and tumorigenic cells. Human NK cells are typically identified by their expression of neural cell adhesion molecule (NCAM, CD56), yet, despite its ubiquitous expression on NK cells, CD56 remains a poorly understand protein on immune cells. CD56 has been previously demonstrated to play roles in NK cell cytotoxic function and cell migration. Specifically, CD56-deficient NK cells have impaired cell migration on stromal cells and CD56 is localized to the uropod of NK cells migrating on stroma. Here, we show that CD56 is required for NK cell migration on ICAM-1 and is required for the establishment of persistent cell polarity and unidirectional actin flow. The intracellular domain of CD56 (NCAM-140) is required for its function, and the loss of CD56 leads to enlarged actin foci and sequestration of phosphorylated Pyk2, accompanied by increased size and frequency of activated LFA-1 clusters. Together, these data identify a role for CD56 in regulating human NK cell migration through modulation of actin dynamics and integrin turnover.

cell biology↗

bioRxiv2021

Single cell trajectory modeling identifies a primitive trophoblast state defined by BCAM enrichment

In early placental development, progenitor cytotrophoblasts (CTBs) differentiate along one of two cellular trajectories: the villous or extravillous pathways. CTBs committed to the villous pathway fuse with neighboring CTBs to form the outer multinucleated syncytiotrophoblast (SCT), while CTBs committed to the extravillous pathway differentiate into invasive extravillous trophoblasts (EVT). Unfortunately, little is known about the processes controlling human CTB progenitor maintenance and differentiation. To address this, we established a single cell RNA sequencing (scRNA-seq) dataset from first trimester placentas to identify cell states important in trophoblast progenitor establishment, renewal, and differentiation. Multiple distinct trophoblast states were identified, representing progenitor CTBs, column CTBs, SCT precursors, and EVT. Lineage trajectory analysis identified a progenitor origin that was reproduced in human trophoblast stem cell organoids. Heightened expression of basal cell adhesion molecule (BCAM) defined this primitive state, where BCAM enrichment or gene silencing resulted in enhanced or diminished organoid growth. Together, this work describes at high-resolution trophoblast heterogeneity within the first trimester, resolves gene networks within human CTB progenitors, and identifies BCAM as a primitive progenitor marker and possible regulator. Summary StatementLineage trajectory modeling identifies multiple human progenitor trophoblast states and defines trophoblast differentiation kinetics, where BCAM-expressing progenitors demonstrate enhanced regenerative ability.

developmental biology↗

bioRxiv2019

Differential nanoscale organisation of LFA-1 modulates T cell migration

Effector T-cells rely on integrins to drive adhesion and migration to facilitate their immune function. Heterodimeric transmembrane integrin LFA-1 (L{beta}2) regulates adhesion and migration through linkage of the extracellular matrix with the intracellular actin treadmill machinery. We quantitated the velocity and direction of F-actin flow in migrating T-cells alongside single molecule localisation of transmembrane and intracellular LFA-1. Our results show that retrograde actin flow positively correlated and immobile actin negatively correlated with T-cell velocity. Plasma membrane localised LFA-1 forms unique nano-clustering patterns in the leading edge, compared to the mid-focal zone, in migrating T-cells. Deleting the cytosolic phosphatase PTPN22, a negative regulator of integrin signaling, increased T-cell velocity, and leading-edge cluster co-localisation of pY397 FAK, pY416 Src family kinases and LFA-1. These data suggest that differential nanoclustering patterns of LFA-1 in migrating T-cells can instruct intracellular signalling linked with the actin treadmill. Our data presents a paradigm where T cells modulate the nanoscale organisation of adhesion and signalling molecules to fine tune their migration speed. This has implications for the regulation of immune and inflammatory responses.

immunology↗