Core C: Proteogenomics Core

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PROTEOGENOMICS CORE (Core C): PROJECT SUMMARY/ABSTRACT Ebola virus (EBOV) and other filoviruses cause devastating pathology, resulting in large part from a dysregulated immune response. At present, our characterization of immune cell-specific responses to EBOV is limited. To address this complex issue, the research projects of this proposal will employ a wide range of OMICS and high- throughput technologies focused at each stage of the “central dogma”; from RNA synthesis, through RNA metabolism, to protein translation and modification. The role of the Proteogenomics Core (Core C) will be to apply cutting-edge massively parallel sequencing and proteomics approaches in support of Research Projects 1, 2, and 3, and to develop novel procedures and technologies to tackle the uniquely complex immune response to EBOV. We will use a combination of short-read (Illumina) and long-read (Nanopore) approaches to characterize epigenetic, transcriptional, and posttranscriptional responses to EBOV infection. Output from sequencing and proteomic analysis will be integrated with the Bioinformatics and Modeling Core (Core D) and deposited in public databases. Finally, these results will be interpreted together with the original main Projects. The Proteogenomics Core comprises a group of experts with experience in the implementation of the wide range of approaches in molecular biology, experimental design, and downstream computational analyses. Core C has a well established track record of innovating novel and cutting-edge methodologies in both next-generation sequencing and mass spectrometry, and can therefore develop and provide state-of-the-art technical support to advance the proposed research to new frontiers. The core will be directed by Dr. Routh, an expert in applying novel sequencing technologies to study RNA virus evolution, transcriptomics, and bioinformatics. Drs. Russell and Widen (Associate Core Leads) are directors of the mass spectrometry and next-generation sequencing facilities, respectively, at the University of Texas Medical Branch. The overarching goal of the Proteogenomics Core is to provide a comprehensive and unprecedented characterization of the “phenome” of cells infected by EBOV, both in cell culture and NHP models. By comparing changes in the epigenetic landscape to observed perturbations in the transcriptome, we will first determine how these events are coordinated and subsequently manifest as changes in the host proteome.