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Colgan, T.

Publications and source records attributed to Colgan, T..

2 recordsLinked to original sources

Analysis of human BBS protein homologues in insects support alternative non-ciliary functions

Cilia and flagella were one of the characteristic traits of the last eukaryotic common ancestor and as such, are highly conserved among eukaryotes. Their proteomic makeup is consequently remarkably similar throughout all eukaryotic lineages. Recently, one subgroup of ciliary transport proteins in mammalian cells, the Bardet-Biedl Syndrome (BBS) proteins, was shown to have the ability to traverse the nuclear envelope, and to engage in protein-protein-interactions that modulate gene expression, signalling cascades, and cell homeostasis. Insects have been critically understudied in cilia biology because of their highly specialised cilia being localised on only a small subset of cell types. In this study, we present evidence that the BBSome, a hetero-octameric ciliary transport complex of BBS proteins, is largely conserved in multiple insect lineages. Using the honeybee Apis mellifera as a study system to explore BBS-associated gene expression, our analyses suggest that not all BBSome-associated genes are expressed equally, indicating possible non-ciliary functions. We also demonstrate that the expression of individual BBS proteins varies significantly between the tissues of queens and males in A. mellifera, especially in neuronal tissue. This result raises the question of what role BBS proteins play in these tissues and whether they are involved in gene regulation in insects. The potential gene regulatory function of BBS proteins should be explored in other eukaryotes due to their high degree of conservation.

evolutionary biology↗

Loss of the Long Non-coding RNA OIP5-AS1 Exacerbates Heart Failure in a Sex-Specific Manner

BackgroundLong ncRNAs (lncRNAs) are known to influence numerous biological processes including cellular differentiation and tissue development. They are also implicated in the maintenance, health and physiological function of many tissues including the heart. Indeed, manipulating the expression of specific lncRNAs has been shown to improve pathological cardiac phenotypes such as heart failure. One lncRNA studied in various settings is OIP5-AS1 (also known as 1700020I14Rik and Cyrano), however its role in cardiac pathologies remains mostly uncharacterised. MethodsWe used data generated from FACS sorted murine cardiomyocytes, human iPSC derived cardiomyocytes, as well as heart tissue from various animal models to investigate OIP5-AS1 expression in health and disease. Using CRISPR we engineered a global OIP5-AS1 knock out (KO) mouse model and performed cardiac pressure overload experiments to study heart failure in these animals. RNA-sequencing of left ventricles provided mechanistic insight between WT and KO mice. ResultsWe demonstrate that OIP5-AS1 expression is regulated during cardiac development and cardiac specific pathologies in both rodent and human models. Moreover, we demonstrate that global female OIP5-AS1 KO mice develop exacerbated heart failure, but male mice do not. Transcriptomics and gene set enrichment analysis suggests that OIP5-AS1 may regulate pathways that impact mitochondrial function. ConclusionsOIP5-AS1 is regulated in cardiac tissue and its deletion leads to worsening heart function under pressure overload in female mice. This may be due to impairments in mitochondrial function, highlighting OIP5-AS1 as a gene of interest in sex-specific differences in heart failure.

physiology↗