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Etherington, R.

Publications and source records attributed to Etherington, R..

2 recordsLinked to original sources

Altered collective mitochondrial dynamics in an Arabidopsis msh1 mutant compromising organelle DNA maintenance

Mitochondria form highly dynamic populations in the cells of plants (and all eukaryotes). The characteristics of this collective behaviour, and how it is influenced by nuclear features, remain to be fully elucidated. Here, we use a recently-developed quantitative approach to reveal and analyse the physical and collective "social" dynamics of mitochondria in an Arabidopsis msh1 mutant where organelle DNA maintenance machinery is compromised. We use a newly-created line combining the msh1 mutant with mitochondrially-targeted GFP, and characterise mitochondrial dynamics with a combination of single-cell timelapse microscopy, computational tracking and network analysis. The collective physical behaviour of msh1 mitochondria is altered from wildtype in several ways: mitochondria become less evenly spread, and networks of inter-mitochondrial encounters become more connected with greater potential efficiency for inter-organelle exchange. We find that these changes are similar to those observed in friendly, where mitochondrial dynamics are altered by a physical perturbation, suggesting that this shift to higher connectivity may reflect a general response to mitochondrial challenges.

plant biology↗

Spatial transcriptomic characterization of COVID-19 pneumonitis identifies immune pathways related to tissue injury

Severe lung damage in COVID-19 involves complex interactions between diverse populations of immune and stromal cells. In this study, we used a spatial transcriptomics approach to delineate the cells, pathways and genes present across the spectrum of histopathological damage in COVID-19 lung tissue. We applied correlation network-based approaches to deconvolve gene expression data from areas of interest within well preserved post-mortem lung samples from three patients. Despite substantial inter-patient heterogeneity we discovered evidence for a common immune cell signaling circuit in areas of severe tissue that involves crosstalk between cytotoxic lymphocytes and pro-inflammatory macrophages. Expression of IFNG by cytotoxic lymphocytes was associated with induction of chemokines including CXCL9, CXCL10 and CXCL11 which are known to promote the recruitment of CXCR3+ immune cells. The tumour necrosis factor (TNF) superfamily members BAFF (TNFSF13B) and TRAIL (TNFSF10) were found to be consistently upregulated in the areas with severe tissue damage. We used published spatial and single cell SARS-CoV-2 datasets to confirm our findings in the lung tissue from additional cohorts of COVID-19 patients. The resulting model of severe COVID-19 immune-mediated tissue pathology may inform future therapeutic strategies. One Sentence SummarySpatial analysis identifies IFN{gamma} response signatures as focal to severe alveolar damage in COVID-19 pneumonitis.

immunology↗