The Laboratory Robotics Interest Group

December 1998 Meeting

High Throughput Screening

Date:        Tuesday, December 8, 1998
Place:       Raritan Valley Community College Advanced Technology Communication Center
                 Route 28 & Lamington Road, North Branch, NJ  08876
Itinerary:  Social Period with Vendor Participation, Food & Refreshments and Poster Session, Lobby -  4:00 to 7:00 PM
                 Presentations and Discussion, Auditorium - 7:00 to 9:15 PM
Pre-Registration: Requested, not required.  Registering will allow us to more accurately gauge seating requirements and refreshment needs.  Indicate names of attendees and company affiliation.
                 Email:  [email protected]
                 Phone: (732)302-1038
                 Fax:     (732)302-9080

Agenda:  An exciting agenda is planned for this meeting centered around High Throughput Screening.  During the Social Period which will feature food and refreshments, there will be a HTS Vendor's Exhibition.  Four presentations with discussion will follow.  Members interested in presenting a poster are encouraged to do so.  Open career positions at your company may be announced or posted.  There is no fee to attend the meeting.  Bring a business card to drop in the registration fishbowl - it eases registration and qualifies you for the rosewood pen set drawing.

Exhibiting Vendors

Presentation:  Automation of the assay development phase of drug discovery
Damien Dunnington (1), Anthony Lozada (1), Hsiu-Yu Tseng (1), Paul Taylor (2) and Frances Stewart (2)
1. Hoechst Marion Roussel, Route 202-206, Bridgewater NJ 08807
2. SmithKline Beecham Pharmaceuticals, 709 Swedeland Road, King of Prussia PA 19406

The early phase of drug discovery, beginning with information and ending with lead compounds, has been re-engineered in recent years to accommodate advances in combinatorial chemistry and genomics. However, the reengineering has not been uniform and a disproportionate effort has been devoted to the screening phase, with relatively little attention to the assay development and hit follow-up stages where substantial bottlenecks persist. As new technologies such as miniaturization and fluorescence are introduced, the gap between an assay conceived by a disease group and the requirements for automated high throughput screening is becoming ever wider. The assay development and reformatting bottleneck has inspired an automated approach toward streamlining and ultimately eliminating this problem. This approach combines established design-of-experiments techniques with robotics and interfacing software, with the ultimate goal of assay configuration in a virtual lab environment and direct interfacing with robotics for execution. Examples will be presented to illustrate the impact of these approaches on assay configuration, robustness and hit detection, and progress toward a fully automated process will be discussed.

Presentation:  A Fully Automated Processing System for Fractionating Natural Products
Robert Corr
Scientist, Natural Products Discovery
Pfizer Central Research

We have designed, built, and integrated a fully automated robotic system that processes crude plant extracts. This system includes bar-coding and weighing, solvent addition and homogenizing, solid phase extraction, evaporation, reweighing, pipetting, and a track robot to move samples through the system.

Presentation:  HTS and Lead Optimization Using FLIPR
Joseph Gunnet, Ph.D.
Principal Scientist, Endocrine Therapeutics
The R.W. Johnson Pharmaceutical Research Institute, Rt. 202, Raritan, NJ 08869

The identification of functional agonists and antagonists for some G-protein coupled receptors (GPCRs) can be done by monitoring intracellular calcium mobilization. FLIPR (Fluorometric Imaging Plate Reader; Molecular Devices Corp.) allows GPCR-induced calcium responses to be accurately and reliably quantitated in an entire 96 well plate. With its CCD camera, FLIPR collects data at rate sufficient to follow the magnitude and time course of GPCR activation in each well. The large amount of information gathered from each well may be analyzed to simply identify hits in HTS or may be analyzed in more detail to optimize leads and ensure receptor-mediated activity. While most of the varibles in using FLIPR are the same as for any 96 well liquid handling system and fluorescent-based assay, performing HTS with FLIPR poses some unique issues and opportunities. We have worked through some of these biological, mechanical and data analysis issues and have successfully run HTS with FLIPR. Improvements in FLIPR hardware and data processing will soon be available and will expand the utility of an already useful instrument.

Presentation:  Validation of Engineered Cell-Based Screens for G Protein-Coupled Receptors
E. William Radany, Ph.D.
Business Manager
Stratagene

G protein-coupled receptors and receptor tyrosine kinases are important targets for drug discovery. High throughput screening (HTS) assays based on ligand binding to these targets may yield biased results depending on the cellular environment in which the cloned receptor resides. The use of engineered cell lines of defined signalling properties with specific receptors provides new tools for HTS assays and the the study of orphan receptors. This presentation will focus on the development of discovery platforms based on reporter gene technology utilizing cells with specific signalling pathways.

Group Update:  There were over 500 attendees to our June Vendors Night!   Ope Odusan from Wyeth-Ayerst Research won the business card drawing and received a handsome rosewood LRIG pen desk set.  We hold a similar drawing at every meeting.   John Wetzel from Synaptic Pharmaceuticals won a Pyrex storage set in the Corning Costar drawing.  Joe Kwasnoski from 3-Dimensional Pharmaceuticals won a Corelle Thermoserver, also from Corning Costar.   The winner of the CD player in the EMAX drawing was Guy Schiehser from Wyeth-Ayerst Research.

The Society for Biomolecular Screening hosted us from September 20-24 at their 4th Annual Conference and Exhibition in Baltimore, MD.   We had a very successful week with hundreds of visitors and 138 new member signups!   Valuable input came in from interested parties across the U.S. and overseas.   There is a lot of interest in forming chapters in Massachusetts, California, North Carolina, and Europe.  If you can help us by being a local representative, please step up.  We held business card drawings every day.  Janet Hartman Johnson (Boehringer Ingelheim), Mojgan Abousleiman (R.W. Johnson PRI), and Howard Miller (Pharmacia & Upjohn) all won rosewood LRIG pen desk sets.  Thank you, SBS!

The Discussion Mailing List debuted on October 12.   It became an immediate hit and now has over 360 subscribers and many interesting dialogues on hardware, software, and methodology.  More information may be found at: https://www.lab-robotics.org/discussion.htm.

ISLAR graciously provided us with a table during the conference October 19-21.  We welcome 211 new members.  Jennifer McMackin (Merck) and Dr. Dave Tapolczay (Cambridge Combinatorial) won rosewood pen sets in the business card drawings.  We identified prospective board members for the Boston, San Francisco, and RTP chapters.  Thank you, Zymark!

We are actively forming the Boston and California Bay Area LRIG Chapters.  Research Triangle Park and Europe are potential candidates.  If you are interested in helping form these chapters by serving on the local board or energizing your peers, please contact us.

We are moving to an email-only meeting notification system.  If you are receiving this mailer in paper form, please send your email address to [email protected]

Mailing Sponsor:  LJL BioSystems  is a proud sponsor of LRIG activities. LJL BioSystems (www.ljlbio.com) designs, produces, and markets instrumentation, reagents, microplates and services that accelerate and enhance the drug discovery process. Our flagship product, Analyst HTS Assay Detection System, is a four-mode analyzer specifically designed for the HTS environment. 

Food & Refreshment Sponsor:  IGEN International Inc. develops detection platforms utilizing ORIGEN?technology, electrochemiluminescence.  Flexible formats allow quantification of specific interactions between two molecules (including: quantitation of analytes, mRNA, K_p's of receptor-ligand pairs, enzyme-substrate activities, interaction of DNA binding-proteins with DNA).  Combining its homogeneous format with a flow cell approach improves sensitivity and precision, while streamlining assay automation.

For more information contact:

Directions (on-line directions):

The Raritan Valley Community College campus lies at the crossroads of Central New Jersey, with Routes 22, 202 and 206 and Interstates 287 and 78 just minutes away. The College is situated on the north side of Route 28 in North Branch.

FROM THE NORTH

From INTERSTATE 287 SOUTH - (From Morristown Area): Take Interstate 287 SOUTH to Interstate 78 WEST. Proceed on 78 WEST for approx. 3 miles to Exit 26 (Lamington/North Branch). At light make a left onto Lamington Road. Proceed on Lamington Road til it ends (approx. 3 miles). At STOP sign make a left onto Route 28 EAST. Entrance to the College will be on your left approx. 1/8 of a mile.

From GARDEN STATE PARKWAY SOUTH - (From North Jersey): Take Exit 142 for Interstate 78 WEST. Proceed on 78 WEST for approx. 26 miles to Exit 26 (Lamington/North Branch). At light make a left onto Lamington Road. Proceed on Lamington Road til it ends (approx. 3 miles). At STOP sign make a left onto Route 28 EAST. Entrance to the College will be on your left approx. 1/8 of a mile.

FROM THE SOUTH

From INTERSTATE 287 NORTH - (From Edison Area): Take Interstate 287 NORTH to the Route 22 WEST exit. After approx. 7 miles (just before the 5th light), exit onto Orr Drive. At the end of Orr Drive make a left at the STOP sign. Make first right into the College.

From GARDEN STATE PARKWAY NORTH - (From the Shore area): Take Exit 127 to Interstate 287 NORTH. Proceed on 287 NORTH to the Route 22 WEST exit. After approx. 7 miles (just before the 5th light), exit onto Orr Drive. At the end of Orr Drive make a left at the STOP sign. Make first right into the College.

From ROUTE 206 NORTH - (From Princeton Area): Take Route 206 NORTH to the Somerville Circle. At the Somerville Circle exit onto Route 28 WEST. Proceed on Route 28 WEST for approx. 4 miles. Entrance to the College will be on your right.

FROM THE EAST

From INTERSTATE 78 WEST - (From Newark Area): Take Interstate 78 WEST. Proceed on 78 WEST and get off at Exit 26 (Lamington/North Branch). At light make a left onto Lamington Road. Take Lamington Road til it ends (approx. 3 miles). At STOP sign make a left onto Route 28 EAST. Entrance to College will be on your left approx. 1/8 of a mile.

FROM THE WEST

From INTERSTATE 78 EAST - (From Clinton Area): Take Interstate 78 EAST to Exit 26 (Lamington/North Branch). Turn right at light onto Lamington Road. Proceed on Lamington Road til it ends (approx. 3 miles). At STOP sign make a left onto Route 28 EAST. Entrance to the College will be on your left approx. 1/8 of a mile.

FROM OTHER AREAS

From NEW JERSEY TURNPIKE - Take the New Jersey Turnpike to Exit 10. After toll, bear left, exit onto Interstate 287 NORTH. Proceed on 287 NORTH to the Route 22 WEST exit. After approx. 7 miles (just before the 5th light), exit onto Orr Drive. At the end of Orr Drive make a left at the STOP sign. Make first right into the College.

From ROUTE 31 NORTH - Take Route 31 NORTH to Route 202 NORTH. Stay on Route 202 NORTH for approx. 10 miles til you come to the Somerville Circle. At the Somerville Circle exit onto Route 28 WEST. Proceed on Rt 28 WEST for approx. 4 miles. Entrance to the College will be on your right.

From PENNSYLVANIA TURNPIKE - Take either Route 78 East, or Route 22 East to Route 78 East. Follow directions above "FROM THE WEST" (From Clinton Area).

FROM THE PARKING LOT (see map of campus)

Follow signs to parking lot #2.

Area Hotels

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