Assay Implementation
Once an assay submitted through PAR-05-147 is assigned to SRMLSC, scientists within the Assay Implementation team will work closely with the assay provider to reproduce, validate, and miniaturize the assay. The assay may also be optimized to improve biological or target selectivity. Assay providers are encouraged to contact a screening center as early as possible and actively collaborate throughout the entire process from assay development to probe optimization, which may also involve screening in secondary assays.
HTS Implementation
The HTS screening facility at Southern Research represents a multimillion dollar investment in equipment and infrastructure. Lucile White leads the HTS Implementation team and has extensive expertise in HTS and enzymology. The robotics platform is built around two Beckman Coulter ORCA rail systems with multiple plate readers for measuring a broad range of endpoints (fluorescence, absorbance, luminescence, etc). Automation of compound handling uses two Biomek FX Liquid Handling Workstations and an Echo 500 to run screening campaigns of up to 100,000 compounds in 384 well plates. SRMLSC is currently expanding capabilities to run assays in 1536 well format and perform image-based high content assays with similar throughput.
Synthetic Chemistry and Probe Optimization
Southern Research has over 40 synthetic chemists on staff with expertise in a wide range of chemical reactions. Dr. Joseph A. Maddry leads the Synthetic Chemistry and Probe Optimization team and has broad expertise in medicinal chemistry. The SRMLSC is equipped with automated synthesis and purification facilities, as well as a scale-up laboratory. Though the MLSCN is not a drug discovery initiative, many of the same physicochemical properties that confer biological activity to drugs (solubility, stability, etc.) will also be important for optimizing molecular probes. Synthetic and computational chemists work together to understand structure-activity relationships for optimizing the activity and selectivity of molecular probes.
Informatics
The SRMLSC informatics team is led by Dr. Subramaniam Ananthan, a medicinal chemist with specific expertise in cheminformatics. Informatics involves a number of different functions in addition to compound tracking data. An Oracle-based, relational database system serves as our data repository prior to uploading the data to Pubchem, which is a publicly accessible database. Computational and medicinal chemists will utilize advanced computing algorithms to relate chemical properties to biological activity. The SRMLSC currently uses software packages such as Sybyl, Pipeline Pilot, and ChemTree to provide chemists the ability to cluster hits and make informed predictions about activity of compounds and chemical classes to direct the design of later generations of molecular probes with optimal biological activity.
