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Southern Research made a large investment in its High-Throughput Screening Center to ensure the highest quality screening services for research projects. The Center consists of a suite of laboratories designed for efficient screening of large compound libraries and has the capacity for screening a wide variety of assay types. The professional staff has in-depth experience and a demonstrated proficiency in transferring bench-top assays to the robotics platform and executing cell-based and biochemical screens. In addition to standard HTS assays, our research team is experienced in running yeast-based assays and assays that require either BSL2 or BSL3 containment.
Since 2006, the Center has processed more than 30 assays per year. One of the more notable aspects of this accomplishment is the breadth of assay types screened at the HTS Center. Over half of these assays were brought in from investigators outside of Southern Research. In addition to the typical assays run in the main lab, we have run sixteen BSL2 containment assays (5 million compounds screened) and four BSL3 containment assays (1.6 million compounds screened). Our Select Agent clearance has allowed us to screen 569,290 compounds against highly pathogenic avian influenza.
| 2004 | 2005 | 2006 | 2007 | 2008 | Total | |
| Total Number of Compounds Screened | 161,100 | 444,355 | 3,217,507 | 3,326,337 | 3,380,997 | 10,697,199 |
| Number of Assays Screened | 18 | 12 | 20 | 27 | 43 | 120 |
| Additional Assays Under Development | 4 | 6 | 13 | 7 | 6 | n/a |
| Number of Hits Confirmed in Dose Response | 40 | 2,044 | 4,096 | 15,643 | 39,837 | 61,660 |
The Center currently conducts five large screening programs for NIH as well as a number of other projects through academic or commercial collaborations.
With growing national concern over emerging infectious diseases, NIH looked to Southern Research to provide high-throughput screening in an effort to discover new antiviral therapeutics. Southern Research established HTS programs for SARS-CoV, highly pathogenic avian influenza, West Nile Virus, as well as influenza and respiratory syncytia viruses.
Southern Research has more than 20 years experience in screening for antibacterials. Our HTS program was initiated with screens in this field. Our Mycobacterium tuberculosis screening project is designed to develop and implement biochemical, target-specific Mtb drug screening assays in an HTS format. Investigators with novel M. tuberculosis biochemical targets are encouraged to submit proposed assays to NIAID for inclusion in the M. tuberculosis HTS target panel. In addition to the biochemical assays, we have implemented whole organism screens in the BSL3 against the virulent Rv strain of Mtb and the avirulent Ra strain. A summary of the program is available at http://www.taacf.org/SRI-HTS.htm.
Building on its 40 years of successful cancer drug discovery research, Southern Research established an HTS program in this field. We have from 5 to more than 10 assays in development at any one time, including cell-based, enzyme, high-content and other novel approaches.
To encourage the use of HTS for neurodegeneration research and drug discovery, NINDS awarded a contract to Southern Research in September 2002. Southern Research provides to the research community a resource for testing assays against a large, diverse collection of compounds. Assay proposals from scientists in the field are solicited by NINDS through notices published in the NIH Guide for Grants and Contracts.
In 2005 Southern Research was named one of nine national extramural screening centers for the pilot phase of the NIH Molecular Libraries Initiative. The Molecular Libraries Initiative , a component of the NIH Roadmap, is "a network of national laboratories, whose aim is to generate small molecule probes by performing high throughput screening, secondary assays, and medicinal chemistry." The ultimate goal of this program is to screen chemical compound libraries against a variety of innovative biological, biophysical, and cell-based assays for biological targets or processes for which there are limited selective and potent small-molecule modulators available to the public. In 2008 Southern Research continued its participation in the second phase of the program, the production phase, with the awarding of the Southern Research Specialized Biocontainment Screening Center grant that acknowledged its unique expertise in high throughput screening of infectious agents. The program is soliciting applications from investigators who have developed innovative assays and are interested in having their assays used to screen large numbers of compounds. Visit the Southern Research Specialized Biocontainment Screening Center.
Having several active and ongoing collaborative research programs, Southern Research continues to seek academic, government and commercial research partnerships in HTS and drug discovery. We are interested in collaborating to pursue government funding for joint efforts including grant applications, competitive contracts, and SBIR/STTRs. From intellectual property income, Southern Research funds an in-house drug discovery program for the purpose of developing commercially relevant intellectual property. For more information on establishing a collaboration, contact David Harris at d.harris@southernresearch.org.
Lynn Rasmussen
Lucile White
News Coverage
Business Contact:
David R. Harris
Director of Strategic Business Development
205-581-2343
d.harris@southernresearch.org
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Bacterial Motility Assay in 384-well Format for HTS [PDF format]