Core 2: RNome Core

Brown University, Providence RI

Investigators

Abstract

Abstract How RNA regulates diverse biological processes from transcription to splicing and translation remains a critical knowledge gap in understanding fundamental mechanisms. RNA is also an important therapeutic tool poised to revolutionize modern medicine (e.g. CRISPR-Cas9) resulting in work that has garnered two Nobel prizes within the last 4 years. However, the IDeA state of Rhode Island lacks the infrastructure to effectively study RNA and support young investigators including the 5 RPLs in this proposal and 6 additional faculty hires who will become core members of the newly formed Brown University RNA Center (29 current member labs). Therefore, the RNome core will provide an integrative suite of RNA biology services and advice to PIs in Rhode Island who are studying RNA while also training the next generation of RNA biologists through courses/workshops. The long term goal of the RNome core is to establish an RNA Biology hub for the IDeA state of Rhode Island which will support and train RNA biologists from Rhode Island and draw funding from neighboring states through courses and workshops. A significant institutional commitment upon funding of this COBRE proposal will be critical to attaining our goal as follows (see letter from Dean Mukesh Jain): 1) $810,953 dollars in instrumentation funding; 2) 6 funded faculty hires who will be future RPLs; 3) a research-track faculty RNome co-director; 4) brand new space/conference center infrastructure. Aim #1: Establish RNome core: mass spectrometry and long-read sequencing for identifying new RNA species and mapping RNA modifications both globally and at single-molecule level in sequence context. Aim #2: Add RNA biology functionality to integrate diverse existing cores allowing them to provide new RNA-related services. There will be no overlap in funding between the new RNome core and existing cores and the RNome core will produce samples which will then be further analyzed in existing cores bringing them new revenue. New services include: 1) RNA immunoprecipitation followed by proteomics for RNA binding protein identification conducted by the Proteomics core; 2) RNA FISH probe generation followed by imaging at the Imaging core; 3) RNA SHAPE secondary structure analysis, massively parallel reporter assays, (MPRAs) and spatial transcriptomics followed by sequencing at the Genomics core; 4) Experimental design for RNA biophysical and structural analysis in the Structural Biology core; 4) Implementing existing and new pipelines for analysis of all RNA-related data from genomics to imaging in the Computational Biology Core. Aim #3: Run a series of summer courses and workshops on RNA biology which will draw participants nationally and locally. Overall, the RNome core will establish the State of Rhode Island as a hub for RNA biology by providing an integrated suite of services and training the next generation of RNA biologists.