Biological Analysis Core

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ABSTRACT – Biological Analysis Core Cellular senescence is a prolonged and generally irreversible growth arrest observed in normal tissue development. While senescence is vital for tissue remodeling, for prevention of malignancy in damaged cells, and in wound healing, the aberrant accumulation of senescence cells is associated with multiple chronic diseases of aging such as atherosclerosis, pulmonary fibrosis, neurodegeneration and others. Senescence is seen as a response to various stressors including telomere erosion, genotoxicity, nutrient deprivation, hypoxia, and mitochondrial dysfunction. The Biological Analysis Core, in partnership with the Biospecimen Core, will be a critical resource for the SenNet proposal by integrating and delivering state-of-the-art technology to investigate senescence at the molecular, single-cell, and whole tissue level. The core is led by a team of highly accomplished research scientists who have successfully utilized these specific platforms in conjunction with previous and/or current clinical studies. Together with the Data Analysis Core, the Biological Analysis Core will generate multimodal atlases that characterize the heterogeneity and spatial distribution of senescent cells at single cell resolution in various tissues including lung, heart, colon, muscle, and skin and across different stages of development consisting of fetal/infant, pediatric (<18 years old), young adults (<35), middle adults (<55), and older adults (>55). To support the consortium and provide the requisite set of senescence maps across different tissues, Biological Analysis Core will utilize a comprehensive repertoire of highly standardized and/or formally validated assay platforms. With the initial focus on lung tissue, we will systematically profile heart, muscle, skin and colon tissues to provide rich tissue maps of senescence across all above-defined age groups. The Biological Analysis Core has the following Specific Aims: 1) to provide high resolution state-of-the-art molecular, cellular, and tissue-level characterization of biospecimens for the purpose of identifying robust biomarkers of senescence and constructing detailed tissue maps, 2) to collect and analyze matching biofluids including blood, cerebrospinal fluid, saliva, and urine, providing a broader interconnection between the senescence maps across multiple tissues and at varying developmental stages, and 3) to develop human-derived microfluidic-based droplet organoids from various tissues to model unique systems amenable to perturbations that test the efficacy of novel drugs for senescence intervention. All of these samples, derivatives, and data will be available to the entire Tissue Mapping Center consortium and our team will work to integrate and optimize all parts of the data generation pipeline, from tissue collection and preservation to data generation, integration, analysis, and interpretation.