OSTP-Sponsored Seminars provide an informative introduction to novel and innovative technologies, as well as great partnership opportunities for the CCR scientific community.

Title: New ABI Integrated Expression Array System
Date of Meeting: Nov. 21, 2003

OSTP and the Microarray Steering Committee

Agenda: Presentation of the new ABI Integrated Expression Array System by Senior scientists from ABI. Issues discussed:

• How the assay allows for the detection of very low levels of gene expression using microarrays and can detect labeled cDNA targets at levels below 10 femtomolar in a hybridization reaction and labeled cDNA targets at levels below 10 femtomolar.
• Demonstrate that the assay has a linear dynamic range of more than 3 logs: from below 10 fM to above 10 pM.
• Gene expression data obtained with a sample range of 1ug to 100ng.
• Annotation of the resultant microarray data for gene expression
• Validation of microarray data with Real-Time PCR assays (TaqMan)

Background Materials:
Applied Biosystems has combined a complete, gene annotated, fully curated human genome transcript data set with high-sensitivity chemiluminescent microarray detection chemistries, and advanced data analysis and management methods to produce a new system for comprehensive gene expression analysis. This provides the basis for an Applied Biosystems Gene Expression System, which they plan on bringing to the market place later this calendar year. The new system enables researchers to survey and measure gene expression over the entire human genome. From a single experiment, a researcher can isolate specific gene expression events, and examine related annotations, and select individual genes for validation of expression and quantitative transcript analysis.

Myriad Genetics' High-Throughput Yeast Two-Hybrid Platform: Research Opportunities for NCI Investigators

Sponsored by the CCR Office of Science and Technology Partnerships
Presentation by: Myriad Genetics

Date: Monday, February 23, 2004
Time: 1:00 - 2:30 PM
Location: Bldg. 37, Rm. 6107

Abstract:

For the last six years, Myriad Genetics has performed high-throughput analysis of protein interactions using its yeast two-hybrid platform, ProNet. During that time, Myriad has analyzed over 4000 proteins, conducted over 50,000 screens and thus far has discovered 8000 protein-protein interactions. A number of extensive protein interaction networks have been delineated, including ones centered around inflammation, glucose uptake, cholesterol efflux, processing of the dementia associated APP protein, HIV viral budding, and B cell signaling. Importantly, only a small fraction of these protein interactions have been observed and described in the literature. Myriad has significantly improved the quality of yeast two-hybrid data by analyzing proteins as a series of overlapping fragments, by efficiently removing false positives and by the use of a suite of over 40 comprehensive libraries derived from a variety of tissues and cells. Myriad has established an extensive relationship with the NIEHS over the last year and is now in a position to offer similar opportunities to additional institutes such as the NCI.

Presentation by: ACEA Biosciences, Inc.

Title: Application of a Microelectronic Cell Sensing Technology to High-Content Cell-based Assays
Date: Thursday, April 15, 2004
Time: 2:00 - 3:30 PM
Location: Bldg. 37, Rm. 6107

Abstract: (From company-provided information)

Cell based assays typically involve labeling cells with dyes or reporters and an end-point detection. We describe the application of a label free, microelectronics-based technology - real-time cell electronic sensing (RT-CES), for information-rich cell-based assays and screening. Microelectronic sensors are incorporated into microtiter plate wells and are used to continuously monitor biological status of the cells in the wells with microtiter plates in an incubator. The entire assay process is monitored and recorded with minute-scale time resolution. A variety of cell-based assays can be performed on the RT-CES platform, including

• cell proliferation
• cell adhesion and spreading
• siRNA-based gene target validation
• cell response profiling to anticancer agents
• cytotoxicity
• NK-cell mediated cytotoxicity
• IgE-mediated mast cell activation and allergy
• receptor-ligand interaction
• environment toxicology
• and many other cell-based assays

In this talk, we describe the RT-CES technology and present the data in several areas including profiling and screening dynamic cell responses to anti-cancer compounds, measuring IgE-activated master cell activation, analyzing ligand-receptor binding. The sophisticated, dynamic cell response curves provide important insight into overall cell-compound interaction and the mechanism of drug action.

Title: Design of Micro/Nanofluidic Devices for Biomedical Applications
Date: Tuesday, April 27, 2004
Time: 1:00 - 2:30 PM
Location: Bldg. 37, Rm. 6041

Speaker: Han Cao, Ph.D., Founder, President & CEO BioNanomatrix

Abstract:

Direct analysis of biomacromolecules such as DNA and protein dramatically improves the speed, accuracy, sensitivity and throughput over conventional methods that rely on tedious steps of cloning, amplification, and bulk solution measurements. Biomolecules such as DNA, RNA protein, and their functional subcellular scaffolds and compartments, are in the scale of nanometers. Thus, the potential of single molecule analysis cannot be fully realized without the help of new disruptive technology. The emergence and advancement of nanotechnology has ushered in a new era in which nanofabricated devices are small, sensitive and inexpensive enough to allow direct observation, manipulation and analysis of single biological molecules from single cells. Applications using nanofluidic devices would allow us to directly visualize and analyze events caused by structural genomic instability with high resolution over large areas, or even at genomic scale in high throughput.

Bionanomatrix is a startup company that is based on technologies developed at Princeton University. They specialize in designing and fabricating high-throughput biomolecular nanoscale ships and devices. Their current nanofluidic chip allows them to stretch and scan hundreds of thousands of genomic DNAs in a linear form, without loss of original genetic or epigenetic information on the genome samples. Applications of these innovative devices include ultra-fast sizing/typing of mega-base viral genome DNA, genomic mapping and comparative/population genomics, proteome sorting, ultra-sensitive detection of bopathogens, and cancer diagnostics. Other nanostructure chips are being developed for molecular sorting, new microarray surfaces for better DNA/protein deposition, and controlled cell growth on chip surfaces for cell based assays.

Title: Bionaut Pharmaceuticals--Using Panels of Engineered Cell Lines to Profile Drug Candidates Based on Signaling Pathway Regulation

Date: Thursday, April 8, 2004
Time: 4:00 - 5:00 PM
Location: Bldg. 40, Rm. 1201-1203
Speaker: Mehran Khodadoust
Chief Scientific Officer
Bionaut Pharmaceuticals
Cambridge, MA

(617) 661-4900 x225
MKhodadoust@BionautPharma.com

Abstract:

Bionaut's Sentinel Pathway Reporter System works by introducing reporter genes into endogenous genetic sites regulated by specific biological stimuli. These reporter genes act as probes, or lightbulbs," that "turn on" with the ligand-trigger to indicate modulation of a pathway by a compound. As such, the reporter gene provides a direct readout of activity at regulated genetic sites, clearly indicating whether a regulatory pathway is active in a particular disease state and, most importantly, whether a drug candidate is able to selectively modulate that role.

Bionaut is building comprehensive panels of Sentinel Lines in well-validated, disease-regulating pathways. Current disease panels include:

* TNF- beta, IL-1, IL-6, and VLA-4 for autoimmune/inflammatory disease;
* EGF, IGF-1, hypoxia, insulin, and TGF-beta for cancer; and
* VEGF, FGF-1, and FGF-2 for angiogenesis.

Demonstration of Stratagene's PathwayAssist Software

Date: Friday, April 16, 2004
Time: 2:00-3:00 P.M.
Location: Building 430 (ABCC), Second Floor conference room
Speaker: Dennis McCormac, Ph.D., Iobion Informatics

Abstract:

Building biological association networks with PathwayAssist™ software. PathwayAssist is a user-friendly software package that allows you to build, visualize and explore biological association networks (BANs). A BAN is an interactive diagram showing biological relationships among different proteins, small molecules and cellular processes from a range of organisms including human, mouse, rat, C. elegans, drosophila, yeast and arabidopsis. Each interaction is annotated with the source references and contains hyperlinks to the source literature. A BAN is built using a biological fact database and each copy of PathwayAssist contains ResNet, a database with over 190,000 biological facts extracted from PubMed. Additional facts can be added from GO, BIND, DIP, KEGG or other custom biological databases. PathwayAssist also supports a variety of query options to allow you to see only types of interactions relevant to your research. In addition, gene expression data from microarray experiments can be overlayed onto a biological association network allowing the user to visualize how strongly genes are up- or down-regulated. These concepts will be covered in this seminar using current biological examples.