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:[email protected]>
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, [email protected]
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
