Cellular Systems Core

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PROJECT SUMMARY/ABSTRACT – Resource Core 2: Cellular Systems Core Investigators in the Joint Biology Consortium (JBC) share a set of challenges that impede utilization of state-of- the-art technologies for research in arthritis and related diseases. Building on success in the first cycle of the JBC, the Cellular Systems Core (CSC) will leverage local resources and economies of scale to cultivate an integrated set of research tools to serve JBC members. The CSC will provide two broad categories of service. First, the CSC will deliver technologies realized through next-generation sequencing. These include single-cell RNAseq, ATAC-seq, T- and B-cell receptor sequencing, genomic DNA sequencing, spatial transcriptomics, CRISPR-based genomic perturbation screens, and autoantigen detection through PhIP-seq and T-scan. Second, the CSC will deliver tools centered on protein detection. These include optimized cytometry by time of flight (CyTOF), tissue mass cytometry, and Luminex-based screens for economical, customizable detection of cyctokines, antibodies, and other proteins. Resulting data will be analyzed through the new Joint Biology Consortium Bioinformatics Core, providing both high-end big-data analysis and structured education and coaching for JBC members, with the goal of developing a community of investigators conversant with advanced computational methods. This program integrates services available through the Brigham and Women’s Hospital Single-Cell Genomics Core and Center for Data Sciences, the Harvard Medical Area CyTOF Core, the Boston Children’s Hospital Division of Immunology, the Broad Institute’s Genomic Perturbation Platform, and other affiliated cores and labs. Progressive optimization of CSC services – now encompassing both cells and intact tissues – will result further through close affiliation with technical and computational leaders of the Accelerating Medicines Partnership (AMP) consortium in rheumatoid arthritis and lupus, ensuring JBC members access to the latest methodologic advances. Service delivery will be led by a scientific team consisting of Harvard CyTOF director Dr. James Lederer supported by associate directors Dr. Kevin Wei and bioinformatician Dr. Maria Gutierrez- Arcelus. This team will ensure that the logistical investment represented by the Cellular Systems Core continues to accelerate innovative translational arthritis research within the JBC.