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Mid Atlantic Chapter

October 1999
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The Laboratory Robotics Interest Group

October 1999 Meeting

High Throughput Screening: Special Topics

Date:        Thursday, October 7, 1999
Place:       Forsgate Country Club, Forsgate Drive, Jamesburg, NJ  08831
                  Phone: (732)521-0070
Itinerary:  Social Period - 3:30 - 6:30 PM
                  Presentations - 6:30 to 9:15 PM
Member Pre-Registration: Requested, not required.  Pre-registering will allow us to more accurately gauge seating requirements and refreshment needs.  Indicate names of attendees and company affiliation.  Pre-register by email with <mailto:andy.zaayenga@lab-robotics.org> or by phone at (732)302-1038.  In order to speed sign-in at the meeting, please bring a business card to drop into the registration box.  There will be a business card drawing for one of our beautiful LRIG rosewood pens.

Agenda:  
The theme of the evening is High-Throughput Screening: Special Topics. After the extended social period from 3:30 to 6:30, the talks will commence leading off with Dr. Sheri Miraglia talking about an exciting new development in scanning laser imaging for high-throughput screening applications. Secondly, we will hear Dr. Susan Bassett talk about the problems of interpreting the voluminous data that we get from HTS and some possible software solutions addressing this problem. Finally, Dr. Dale Christensen will talk about a novel approach in finding small molecules that interact with receptors for which ligands are not necessarily known. Taken together these speakers, who are coming far and wide from California, New Mexico, and North Carolina, will ensure a stimulating evening. As always, there is no registration fee or dues, and food and refreshments will be served throughout the social period. Registration is encouraged for us to accurately gauge the size of the meeting.

There are hotels nearby for attendees who wish to stay overnight.

There will be a Job posting board at the social. Please encourage your recruiters to give you material to post and distribute. Openings may also be posted at https://www.lab-robotics.org/careers.htm

Members interested in presenting a scientific poster are encouraged to do so. Please contact us to arrange for poster space.

There is no fee to attend the meeting.

Presentation:  High-Throughput Screening Applications of a Novel Scanning Laser Imaging Technology
Sheri Miraglia, Ph.D., Senior Scientist, PE Biosystems

The increasing number of compounds available for screening in drug development has driven the requirement for higher throughput screening technologies, as well as unique technologies that address a broader application portfolio. Our laboratory has been involved in the development of multiplexed mix-and-read assays using Fluorometric Microvolume Assay Technology (FMAT). FMAT is a fluorescence based assay system that incorporates a laser scanner and optical detection system that provides a direct measurement of cellular or bead-based fluorescence on a well-to-well and on an individual cell/bead basis. This design is ideal for the homogenous identification of hits in primary screening, as well as for lead optimization in the form of IC50 determinations, and for assessment of lead compound cytotoxicity. Fluorescent beads of various sizes can be distinguished from one another, allowing the multiplexing of two or more targets present on different sized beads in the same well. In addition, the digitized image data is compiled from two PMTs permitting the development of multiplexed assays based on dye color. A variety of different mix and read applications for FMAT will be described, including peptide-receptor ligand interactions, and multiplexed bead based immunocapture assays. The results of a novel high-throughput screen performed in collaboration with a major Pharma oncology group will also be discussed. Employing a simple mix-and-read Annexin V binding assay, a variety of purified natural products were identified that are potent inducers of apoptosis in tumor cells. Taken together, the data to be presented will demonstrate the versatility and feasibility of fluorescence-based homogeneous and multiplexed assays for a variety of cell-based and molecular targeted screens used in drug discovery.

Presentation:  Harnessing the Power of Computational Intelligence to Identify Leads in HTS
Susan I. Bassett, Ph.D., Executive Vice-President, Global Technology Operations, Bioreason, Inc.

With high-throughput screening systems in place and beginning to produce data reliably, the data analysis and interpretation becomes a bottleneck in the process of moving more high-quality leads to the clinic. The decision-making processes that go into lead discovery, evaluation, and development are quite complex, and can benefit from judicious use of appropriate computational intelligence techniques. Knowledge-based reasoning systems that capture the decision process of a pharmaceutical chemist during lead identification and development and aid in decision support will be presented in this talk. Bioreason's HTS data interpretation systems are an example of an automated solution aimed at helping identify top quality lead candidates while minimizing costly mistakes. The fundamental aspects of technology for combining computational intelligence techniques with knowledge discovery from data mining to this end will be presented.

Presentation:  Molecular Braille: A Novel Technology for Identification and Characterization of Compounds that Modulate Receptor Function
Dale J. Christensen, PhD., Senior Scientist
Novalon Pharmaceutical Corp., 4222 Emperor Blvd., Suite 560 Durham, NC 27703-8466, Ph 919-474-8888 x34, Fax 919-474-0103, dchristensen@novalon.com

Many receptor proteins in cellular signaling pathways undergo significant conformational changes in response to a signal molecule. Nuclear hormone receptors are ligand-dependent transcription factors. Ligand binding to these receptors results in conformational changes that expose binding sites for coactivator or corepresser proteins. The estrogen and androgen receptor are well validated drug targets that have a significant clinical utility while orphan nuclear receptors such as PPAR are beginning to play an important role in modern drug discovery. Molecular Braille has been developed to identify and characterize compounds that modulate the conformation of these receptors. Using a series of conformation-sensitive probes, the conformation that the receptor adopts in response to ligand binding can be evaluated using an in vitro time-resolved fluorescence assay and an in vivo luminescence assay. This technology can be used to identify new ligands, distinguish between classes of ligands, and guide lead optimization.

Directions:

From the North or South: Take the New Jersey Turnpike to Exit 8A - Exit the left ramp for Jamesburg (Route 32 East) - Continue straight for 1 1/4 miles through traffic light - Forsgate Country Club is on your left - Use the Clubhouse Entrance (second left).

From Princeton: Route 1 to Scudders Mill Road East - Continue on Scudders Mill Road and make a left at the 5th traffic light onto Dey Road - Continue on Dey Road to the end  - Make a left  - At 2nd traffic light (Route 32) make a right - Continue straight for 1 1/4 miles through traffic light - Forsgate Country Club is on your left - Use the Clubhouse entrance (second left).

For an interactive map:

Visit The Laboratory Robotics Interest Group homepage at https://www.lab-robotics.org


Send mail to andy.zaayenga@lab-robotics.org with questions or comments about this web site.
Copyright ?1999 Laboratory Robotics Interest Group
LRIG?is a trademark of the Laboratory Robotics Interest Group
Last modified: October 15, 2004

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