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4:00-6:00pm Conference Pre-Registration

MAIN CONFERENCE

MONDAY, MAY 12

7:30am – 6:00pm Registration Open

7:30am Morning Coffee

8:30  Chairperson’s Remarks
Andrew Napper, Ph.D., Director of High-Throughput Screening, Penn Center forMolecular Discovery, University of Pennsylvania

8:40 BacMam Virus Gene Delivery: A Versatile Assay Development Tool
Tom Kost, Director, Biological Reagents & Assay Development, GlaxoSmithKline, R&D
As an alternative to the development of stable cell lines BacMam virus gene delivery provides a flexible approach for developing recombinant cell based transient assays. BacMam viruses can transduce a wide variety of cell types and provide the capability of controlling the expression level of target proteins. This presentation will focus on the background of this approach and some examples of its application in building assays.

9:10  High-Throughput Screening with Infectious Agents: Choices and Strategies
Lucile White, Manager, High-Throughput Screening Center and Enzymology Laboratory, Drug Discovery Division, Southern Research Institute
High-throughput screening and containment such as BSL3 are not normally associated. Equipment for HTS is often too large for standard Biological Safety Cabinets and space is often limited for large HTS operations. In order to conduct HTS screening campaigns under containment we have developed methodology to screen efficiently. Results from campaigns with both viruses and bacteria in BSL2 and BSL3 will be discussed.

9:40  Speaker to Be Announced

10:10 Networking Coffee Break

10:40 From uHTS to Chemical Probes
Peter S. Hodder, Ph.D., Scientific Director, Lead Identification; Associate Professor, Molecular Therapeutics, The Scripps Research Institute
The Scripps Research Institute has implemented the various core functions necessary to support a successful drug discovery enterprise in an academic setting. These include the expertise and technology to enable assay development, uHTS campaign execution in a miniaturized format, compound profiling, DMPK activities and a mature medicinal chemistry program. This presentation will focus on case studies initiated by cell-based uHTS campaigns, the specific technologies and strategies that facilitated the discovery of publicly available chemical probes, as well as a discussion of the utility of the probes themselves.

11:10 Quantitative High-Throughput Screening (qHTS)
Douglas Auld, Ph.D., Group Leader, Genomic Assay Technologies, NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health
The U.S. National Institute of Health Chemical Genomics Center (NCGC) is innovating new uses of existing technologies to facilitate construction of chemical genomic databases and the development of chemical probes for the study of protein and cell functions. This talk will focus on the development of a platform called “quantitative HTS” (qHTS) that allows large chemical libraries (200K) to be screened as a concentration-titration series creating a database of concentration-response curves (CRCs) for every compound. This process includes innovative compound management approaches to incorporate flexibility/resilience into the screening process, efficient use of reagents through employment of miniaturized 1536-well systems, and automated CRC fitting/classification algorithms that greatly simplify the analysis of diverse types of CRCs. The talk emphasis will be the application of qHTS to cell-based assays.    

11:40 Integration of Complex Cell-Based Assays with Miniaturized HTS
Andrew Napper, Ph.D., Director, High-Throughput Screening, Penn Center for Molecular Discovery, University of Pennsylvania
As part of the Molecular Libraries Screening Center Network (MLSCN), the Penn Center for Molecular Discovery (PCMD) has a mandate to discover novel chemical probes to be made available to the wider drug discovery community.  To this end, the PCMD has set up automated HTS infrastructure to screen complex cell-based assays against a library of 250,000 compounds.   Robust assays have been achieved by optimization of several critical parameters.  Reagents and
cells are dispensed under sterile conditions, and compounds formatted in 1536- and 384-well plates are transferred by tips, pintool or acoustic dispense.  Mixing and centrifugation as needed are integrated with the robotic screening platform.  Plates sealing and incubation are tailored to the specific assay to minimize edge effects and other factors that reduce assay performance.  Successful screens to date include luminescent detection of specific gene expression in yeast and malarial parasite invasion of red blood cells, fluorescence monitoring of the viability of fungal biofilms, and the use of AlphaScreen to measure cyclic AMP levels following GPCR activation.  In addition to these plate-based assays, multiplexed microarray-based detection of quantum dots provides a profile of expression and post-translational modification of intracellular proteins.  Complete HTS results are available on PubChem, allowing investigators to use data mining to identify compounds with novel profiles of cellular activity.

1:10  Session Break

1:40 Chairperson’s Remarks
Robin Felder, Ph.D., Professor, Pathology, University of Virginia

1:45  Warming up a Cold Idea: Frozen Cells as Reagents for Automated 3D Cell Culture
Robin Felder, Ph.D.
High-content screening (HCS) and cell-based assays are becoming principal tools in pharmaceutical discovery laboratories. Research cells (e.g., HEK293, CHO) and primary cells (e.g., kidney, liver, brain, endothelium) have utility in locating and refining new therapeutic targets. The culture of these cells is time consuming and leads to assay variability. Using previously characterized lots of frozen cells that can be directly incorporated into high-throughput assays will decrease labor while increasing the consistency of data. Global Cell Solutions has created a novel microcarrier (GEM(tm)) for automated 3D cell culture upon which cells can be expanded and cryopreserved. This cell laden GEM can then be thawed and incorporated directly into high-throughput assays without removal from the substrate. The benefits of automating this process and the quantitative results obtained from our NSF grant, “Cryopreserved Cells as Reagents,” will be discussed.

2:15  3-D Tissue Cultures for Safety and Efficacy Assessment of New Drug Candidates
Dawn R. Applegate, Ph.D., President & CEO, RegeneMed, Inc.
Keys to regenerating in vivo function in vitro are co-culturing all cell types of a native tissue in three-dimensional interconnecting porous structures, both being required to enable cells to assume natural function outside the body. In this environment cells can co-locate, facilitating cell-cell communication to induce expression of all of the extracellular matrix proteins (ECM) and growth factors of natural tissue, and subsequently undergoing cell-ECM interaction to form tissue architecture and thereby impart physiologic function in vitro. The resultant tissue co-cultures express long term tissue-specific function. The first 3-D tissue developed for drug discovery is liver co-culture grown in standard multiwell plates for seamless integration into pharma s standard workflow. These liver co-cultures express sustained tissue-specific function (90 days), enabling the systems to replace the short-term poor predictive function of industry-standard hepatocytes in metabolism and toxicity (ADMET) assessment of new drug candidates.

3:00  Grand Opening Refreshment Break in the Exhibit Hall

3:40  Stem Cell-Based Screening
John Hambor, Ph.D., Chief Executive Officer, Cognate BioServices

4:10  Speaker to Be Announced

4:40  Panel Discussion: Cell-Culture: Increasing Efficiency and Throughput in Support of Cell-Based Screens
Moderator: Richard Del Mastro, Ph.D., Director, R&D, GIBCO Research Area Manager Cell Culture Systems, Invitrogen Corp.

5:10  Happy Hour in the Exhibit Hall 

6:10 End of Day

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