This is a project which is currently making use of HPC facilities at Newcastle University. It is active.
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This project investigates how p16INK4a- and p21CIP1-associated cellular senescence contributes to myocardial ageing, cardiovascular disease and adverse cardiac remodelling. The work will use transcriptomic and spatial data from human myocardial tissue, alongside in vitro models of human cardiomyocytes, cardiac fibroblasts and endothelial cells, to define senescence-associated gene expression, inflammatory and fibrotic signalling, cell-type specificity and tissue microenvironmental changes. The overall aim is to understand whether p16- and p21-associated senescence represent distinct biological states in the myocardium and to identify molecular pathways that may inform future biomarkers or senescence-targeted therapeutic strategies.
The project will use the HPC facility for analysis of high-dimensional transcriptomic, single-nucleus RNA sequencing and spatial transcriptomic datasets. Workflows will include quality control, alignment, feature counting, dimensionality reduction, clustering, differential gene expression, pathway enrichment, spatial mapping and integration of multiple omics datasets. Software is expected to include R, RStudio/R scripts, Seurat, Bioconductor packages, ggplot2, clusterProfiler, Python, Cell Ranger, Space Ranger, Harmony, LIGER and other established bioinformatics tools for single-cell and spatial transcriptomic analysis. The compute activity will mainly involve batch processing of sequencing-derived count matrices, memory-intensive integration of large gene-expression objects, statistical modelling, visualisation and reproducible analysis pipelines.