Southern Research Institute (Southern Research) offers the Southern Research Specialized Biocontainment Screening Center (SRSBSC).for participation in the Molecular Libraries Program. The SRSBSC will provide a platform for assays requiring Biosafety Levels 2 and 3 (BSL2/3) for HTS. The current state-of-the-art in HTS in virology is limited by existing technology, which is primarily focused on screening of viral protein/enzyme-based targets or measuring the cytopathic effect of some viruses. These assay formats are highly amenable to HTS. However, a review of the literature reveals outstanding innovation by numerous laboratories in assays that can be adapted to an HTS platform, but which are not amenable to HTS because of the current state-of-the art of the instrumentation and reporter probes used in these analyses. Hence we will provide the opportunity to include these other lower throughput screening methods in the Network. The Center will have five functional Cores: (1) Assay Development/Adaptation/Implementation;(2) HTS;(3) Informatics, (4) Administrative and Management and (5) Research. The overarching objective is to provide 5 assays per year that identify molecular probes for protein function and pathways involved in virus-cell interactions, which will lead to hit identification and characterization. Further, we will work with the Specialized Chemistry and/or Comprehensive Screening Centers to develop a strategic plan for hit-to-probe optimization. It is our goal to meet the following milestones in Year 1: (1) Provide oversight and logistics required to move 5 assays forward through different Cores, (2) Enhance performance of dual reporter assays to accelerate 2 screening platforms in the BSL3: Reader and microscope technologies, (3) Provide technological solutions tooptimize throughput and robustness of 5 assays for automation in BSL2/3 containment, (4) Develop 5 counter screens unique to 'the 5 screening campaigns with Assay Provider, (5) Provide screening of 5 assays of 300,000 compounds, dose response of hits and curate associated data for public dissemination. In all of these activities, we will seek to integrate our Center with the MLPCN Research Network to promote collaborations,integrative solutions and sharing of data to achieve the goals of the Molecular Libraries initiative.
The SRSBSC will contribute to the MLPCN Research Network by providing detection screening platforms requiring BSL2/3. Successful execution of the SRSBSC will provide live viral-based assays that yield novel molecular probes for virus and host targets, which will reveal give insight into how proteins and pathways function. Finally, it should not be overlooked that SRSBSC efforts should accelerate the discovery of targets for therapeutic intervention, and reveal biomarkers of infection that could be used for early diagnosis of viral infections.
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