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2010 Archived Content

Evaluating Novel Technologies for Cell Based Screening Banner 

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7:00 am Registration and Morning Coffee

Miniaturization: The How and Why of Making Assays Smaller 

8:15 Chairperson's Opening Remarks

Daniel G. Sipes, Director, Advanced Automation Technologies, Genomics Institute of the Novartis Research Foundation

8:25 Cell-Based Assay Miniaturization and Automation at GNF: Screening and More

Daniel G. Sipes, Director, Advanced Automation Technologies, Genomics Institute of the Novartis Research Foundation

At GNF, we recently expanded the utility of our proprietary automated platforms for cell-based screening more deeply into the drug discovery process. We have utilized GNF-built automation, as well as other commercially available technologies, to enable cost effective and rapid cell-based compound profiling. In addition, this approach has enabled scientists to run iPSC assays on a scale not otherwise practical.

8:55 Novel Methodologies and Technologies for Cell Based Screening at the Nano-Scale     

Anthony Davies, Ph.D., Director, Trinity HCA, Department of Clinical Medicine, Trinity College Dublin

Miniaturization of cell based assays can be technically difficult and costly to deploy. Utilising the very latest liquid handling, imaging systems and newly developed environmental control technologies, a new and relatively straightforward means of setting up cell based assays for high content analysis in a micro array format is presented. By adopting these approaches we have overcome many of the technical issues associated with the use of micro-arrays in cell based screening.

9:25 Ultraminiaturization for High-Throughput Biotechnology

Scott Diamond, Ph.D., Founding Director, Penn Center for Molecular Discovery, E. Humphrey Chair of Chemical and Biomolecular Engineering, University of Pennsylvania

High-throughput experiments require the deployment of various libraries of compounds, siRNAs, genes, enzymes, or enzyme substrates. We developed tools for screening chemical libraries in nanoliter reactions on microarrays at up to 6000 compounds per glass slide. Examples from our laboratory include the identification and development of novel inhibitors (MDL28170, disulfiram, and oxacarbazates) of the SARS coronavirus, the mapping of protease active sites, and the functional testing of human and mouse blood on patterned surfaces and in microfluidic devices.

9:55 Networking Coffee Break

10:25 Applying HTS technologies toward the rapid biological characterization of small molecules.

Fred King, Ph.D., Research Investigator, The Novartis Institute of Biomedical Research

Cell-based HTS often produce lead compounds with notable biological properties, yet identifying their respective cellular target and/or MoA is often a resource intensive exercise. To this end, we have developed an HTS amenable platform consisting of low cost reporter gene assays. The output provides compound activity profiles that can be used for MoA determination along with a number of additional applications.

10:55 Doing More With Less: Advances in Miniaturization for uHTS

Eric Johnson, Ph.D., Senior Research Fellow, Automated Biotechnology, Merck Research Laboratories

With the inception of screening small molecule libraries to identify leads in the drug discovery process, many groups have realized the potential benefits of assay miniaturization including savings of cost, time, and compound consumption. While the benefits may be somewhat obvious, the practical approaches of how to achieve an assay suitable for ultra high throughput screening are not. I will discuss some of the tactics we have used to generate assays suitable for screening in 1536-well and 3456-well plates.

11:25 A 3-D Cell Culture Microarray System for Early Toxicity Screening

David Rozzell, Ph.D., President and CEO, Solidus Biosciences, Inc.

A 3-dimensional cell culture microarray platform to screen for both acute toxicity and metabolism-induced toxicity of compounds will be described. Using a miniaturized 3D cell-culture array containing 1,080 individual cell cultures in a spatially addressable format the effects of Phase I and II metabolism are emulated, leading to an approach for assessing the toxicity of early-stage drug candidates. 

11:55 – 12:25 pm Luncheon PresentationSponsored byApplied Biosystems NEW I
Characterizing Protein-Protein Interactions in Cell Lysates Using Proximity Ligation Assay
Kazuya Machida, Ph.D., MD, Department of Genetics and Developmental Biology, University of Connecticut Health Center
Protein-protein interactions drive the assembly of signaling complexes to transduce signals to downstream effectors. In tyrosine kinase pathways, tyrosine phosphorylation of specific sites creates binding sites for phosphotyrosine recognizing modules such as SH2 and PTB domains. We have developed a sensitive method to quantify binding sites for modular protein domains based on Proximity Ligation Assay and quantitative PCR, called TaqMan® Protein Assays (TPA-qPCR). We present applications of the approach to characterize activation status of a growth receptor-stimulated receptor using SH2 domain probes. This study illustrates the potential of TPA-qPCR method as a new high throughput tool for protein-protein interaction analysis.

12:25 – 1:55 pm Luncheon PresentationSponsored byAttana II
Kinetics on Cells-Bridging the Gap between Traditional Biosensor and Cell Based Assay
Camilla Käck, Ph.D., Research Scientist, Attana
The development of new pharmaceutical antibodies is a long and expensive process with sharply increasing costs during clinical trials. Attana Cell™ 200 is a QCM based biosensor that provides highly informative data about drug candidates in preclinical stage, thus improving selection and reducing the risk of late failures.
Two typical examples where the Attana Cell 200 proved to be beneficial will be presented; 1) study of a glycoprotein to be used as a diagnostic tool for early detection of metastatic colorectal cancer, 2) characterization of modified Herceptin® designed for  targeted immunotherapy in cases of breast and ovarian carcinomas.


1:25 Chairperson's Remarks

Clay Scott, Ph.D., Associate Director, Lead Generation, AstraZeneca Pharmaceuticals

1:35 Orthogonal Compound Differentiation:  Where do Label-Free technologies have the greatest impact?

Matthew Todd, Ph.D., Research Fellow, Team Leader, Lead Generation Biology , Johnson & Johnson, PR&D

There are innumerable tools for measuring pharmaceutical target activity, both directly (sometimes exploiting label-free technologies) and indirectly (often exploited for programs designed to discover lead molecules via cell based assays).  If not resourced constrained, what would be the most complete discovery strategy?  Practically, what fraction of these assays yield independent information?  And how can one efficiently develop all those assays?

2:05 Problems and Promise of Cell-Based Assays in Compound Identification

Charles Lunn, Ph.D., Research Fellow, New Lead Discovery, Merck Research Laboratories

Modern high throughput biochemical methods allow efficient interrogation of compound libraries using cell-based assays. However, biases inherent in many of these assay strategies may limit the ability to identify compounds of potential therapeutic interest. We will discuss this issue, using an example of a compound with unexpected pharmacology identified using a biochemical screen, then profiled using cell-based assays to determine pharmacology and a potential mechanism of action. We will then discuss the potential value of optical biosensors as a screening method that may eliminate some problems associated with biased cell-based screening programs.

2:35 Comparing Impedance- and Optical-Based Biosensors for Use in GPCR Drug Discovery

Clay Scott, Ph.D., Associate Director, Lead Generation, AstraZeneca Pharmaceuticals

The current technologies for label-free whole cell assays utilize either an impedance-based or an optical-based biosensor. Experiments were performed on the CellKey (impedance), SRU BIND (optical) and Epic (optical) instruments to assess their ability to distinguish which G-protein pathways are activated by different ligand-receptor pairs and quantitative pharmacology of GPCR signaling through Gs, Gi and Gq pathways. Examples of dual signaling were observed: comparisons to more traditional readouts will be described.

Sponsored by
 3:05 The CellKey® System.  A Superior Solution for Gαi-Coupled and Gαs-Coupled GPCR Analysis
Ryan McGuinness, Senior Application Scientist, Molecular Devices CorporationDuring this presentation attendees will be updated on recent work performed with Molecular Devices’ label-free CellKey® System.  Case study and end user data will be highlighted to demonstrate the superiority of CellKey assays over traditional assays for Gαi and Gαs-coupled GPCRs in terms of robustness and reproducibility, and ease of use.  We will also discuss how the CellKey system’s sensitivity to endogenous levels of target receptors permits more informed decisions throughout the drug discovery process from target identification and validation to follow-up screening and SAR.

3:20 Sponsored Presentation (Opportunity available) 

3:35 Grand Opening Refreshment Break in the Exhibit Hall



4:15 Shifting Sands of Pharmaceutical Discovery 


Cris Waller Chris L. Waller, Ph.D., Senior Director, HealthCare Informatics, Medical Business Technology, Pfizer, Inc. 

Gary PeltzGary Peltz, M.D., Ph.D., Professor, Anesthesia, Stanford University 

Marvin BayneMarvin Bayne, Ph.D., Vice President, Head, Discovery Technologies, Merck & Co. 

Thomas BocanThomas Bocan, Ph.D., Senior Director, Head, Pre-clinical BioImaging Center, Pfizer Global R&D,, Pfizer, Inc. 

Peggy Guzzie-PeckPeggy Guzzie-Peck, Ph.D., DABT, Vice President, Head, Toxicology, Pathology & LAM, Johnson & Johnson, Pharma R&D 

Key questions to be addressed: 

  • How does academic research impact pharma drug discovery? 
  • How does the creation of cross-pharma pre-competitive collaborations impact drug discovery, spanning chemistry, biology, and knowledge management? 
  • Adoption of new technologies, such as, molecular Imaging: Can it help drug discovery and how quickly? 
  • How effectively and efficiently can we collaborate to develop safer drugs? 

5:45 Happy Hour in the Exhibit Hall

6:45 End of Day

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