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Biology subjects

Langton, P. F.

Publications and source records attributed to Langton, P. F..

2 recordsLinked to original sources

PECAn, a pipeline for image processing and statistical analysis of complex mosaic 3D tissues

Investigating organ biology requires sophisticated methodologies to induce genetically distinct clones within a tissue. Microscopic analysis of such samples produces information-rich 3D images. However, the 3D nature and spatial anisotropy of clones makes sample analysis challenging and slow and limits the amount of information that can be extracted manually. Here we have developed a pipeline for image processing and statistical data analysis which automatically extracts sophisticated parameters from complex multi-genotype 3D images. The pipeline includes data handling, machine-learning-enabled segmentation, multivariant statistical analysis, and graph generation. This enables researchers to run rigorous analyses on images and videos at scale and in a fraction of the time, without requiring programming skills. We demonstrate the power of this pipeline by applying it to the study of Minute cell competition. We find an unappreciated sexual dimorphism in Minute competition and identify, by statistical regression analysis, tissue parameters that model and predict competitive death.

cell biology

Xrp1 and Irbp18 trigger a feed-forward loop of proteotoxic stress to induce the loser status

Cell competition induces the elimination of less-fit "loser" cells by fitter "winner" cells. In Drosophila, cells heterozygous mutant in ribosome genes, Rp/+, known as Minutes, are eliminated via cell competition by wild-type cells. Rp/+ cells display proteotoxic stress and the oxidative stress response, which drive the loser status. Minute cell competition also relies on the activities of the transcription factors Irbp18 and Xrp1, however how these contribute to the loser status is partially understood. Here, we show that Irbp18 and Xrp1 induce the loser status by promoting proteotoxic stress. We find that Xrp1 is necessary for Rp/+ - induced proteotoxic stress and is sufficient to induce proteotoxic stress in otherwise wild-type cells. Xrp1 is also induced downstream of proteotoxic stress and required for the competitive elimination of cells suffering from proteotoxic stress. Our data suggests that a feed-forward loop between Xrp1, proteotoxic stress, and Nrf2 drives Minute cells to become losers.

genetics