Immediately preceding Genomic Sample Preparation, April 26-27, 2001.

Special Discounted Registration Rates for Combined Registration with Genomic Sample Preparation

Corporate Sponsors:
Corporate Support:

Sponsoring publications:		Web Partner
Current Drug Discovery Drug Discovery and Development Drug Discovery Today Micromachine Devices Disease Markers Genome Biology Perspectives in Drug Discovery Journal of Computer Aided Molecular Design		Lab-on-a-Chip.com

This technology finds itself center stage thanks to the successful decoding of the human genome. Regardless of its enormous potential, only recently has the number of application papers surpassed that of review articles. In other words, we have a technology that works well despite, rather than because of, our understanding of the subject. Once again this Boston conference will highlight the best advances in the hardware production and manufacturing of these machines, but we will also examine critical questions to the application of these tools, to their data analysis, and to the tacit assumptions researchers have made in the larger biological picture-sometimes without enough skepticism or innovation.

Workshop Microarray Informatics, April 22 click here  for details.

KEYNOTE PRESENTATION
Dr. Andrei Mirzabekov, Argonne National Laboratory

Session Chairs
Dr. Yoshinobu Baba, University of Tokushima (Japan)
Dr. Michael Cardone, Massachusetts Institute of Technology
Dr. Steve Gullans, Harvard University
Dr. Jörg Hoheisel, German Cancer Research Center (Germany)
Dr. Inge Jonassen, University of Bergen (Norway)
Dr. Renae Lin Malek, The Institute for Genomic Research

Additional Speakers
Dr. Ezra S. Abrams, Mosaic Technologies, Inc.
Dr. Steve M. Clark, GlaxoSmithKline Pharmaceuticals, Inc.
Dr. Paul Diehl, Agilent Technologies
Dr. Anju Dang, Ciphergen Biosystems, Inc.
Dr. Jonathan S. Dordick, Rensselaer Polytechnic Institute
Dr. Glen A. Evans, Egea Biosciences, Inc.
Dr. Stephen Friend, Rosetta Inpharmatics, Inc.
Dr. Sandeep Gulati, ViaLogy Corporation
Dr. David Hanzel, Amersham Pharmacia Biotech
Dr. Debra Hoover, Corning Incorporated
Dr. Ian Humphery-Smith, Glaucus Proteomics B.V. (The Netherlands)
Dr. Olli Kallioniemi, National Human Genome Research Institute, National Institutes of Health
Dr. Greg Kirk, Millennium Pharmaceuticals, Inc.
Dr. Robert R. Klevecz, Beckman Research Institute of The City of Hope Medical Center
Dr. Brent L. Kreider, Phylos, Inc.
Dr. Gavin MacBeath, Harvard University
Dr. David A. Nielsen, InforMax, Inc.
Dr. Steffen Nock, Zyomyx, Inc.
Dr. Wilhelm Plüster, Eppendorf AG (Germany)
Dr. Barry Schweitzer, Molecular Staging Corporation
Dr. Soheil Shams, BioDiscovery, Inc.
Dr. Siqi Tan, Incyte Genomics, Inc.
Dr. Tuan Vo-Dinh, Oak Ridge National Laboratory
Dr. Bernhard H. Weigl, Micronics, Inc.
Dr. Tom J. Whitaker, Atom Sciences, Inc.
Dr. William G. Whitford, PHASE-1 Molecular Toxicology, Inc.

Production Technology High-Throughput Production Considerations Advanced Attachment Chemistry The State of the Ink Jet Art New Quality Standard Photolithography Develops Microfabrication/Design Microarray of Gel-Immobilized Compounds on Chip Diffusion-Based Separation and Detection Single DNA Molecule Analysis Rapid and Flexible Platform for Array Synthesis Hundreds or Thousands of Tissue Specimens in a Single Experiment Sui Generis Platform Generation Detection Novel Laser Approach Quantum Interferometric Enhancement Dendrimer Detection Multilabel DNA Mapping Rolling Circle Amplification as Applied to Protein

Bioinformatics Wavelet Decomposition Platform-Independent Bioinformatics Getting the Signal Straight Integration for Downstream Considerations The Entire Genome as a Sensor Pad Applications Direct Application in Drug Discovery Retinoic Acid Stimulation of Hematopoietic Cells Synthetic Evolution Multi-enzyme-Containing Microchips Rat Fibroblasts Transfected with Src Mutant and Wild-Type Constructs Gene Density Quantification Proteins High-Affinity Antibody Mimics Highly Parallel Miniaturized Technology for Proteins Deciphering Protein Function Benchtop Proteomics Proteins Arrayed on MALDI and Glass Surfaces The Human Proteome in Health and Disease

 

Monday, April 23

7:30 am Registration, Poster and Exhibit Viewing, and Light Continental Breakfast

 

Production Technology

 

8:30 Chair's Opening Remarks
Dr. Jörg Hoheisel, Head, Functional Genome Analysis, German Cancer Research Center

8:35 High-Throughput DNA Microarray Production: Materials Selection and Systems Design
Dr. William G. Whitford, Principal Scientist, PHASE-1 Molecular Toxicology, Inc.
For-profit manufacturing and core-facility type production of DNA microarrays on derivatized glass substrates can require systems of high production rates, efficiency, consistency and economy not considered by low-volume suppliers. Topics examined include: selection criteria for robotic spotters, substrate derivatization, probe binding chemistries, configuration of existing and/or novel instrumentation applications and software, design of production procedures and logistics, approaches to post-fabrication processing, as well as production batch and quality control issues. A review of commercially available pen-deposition type DNA microarray production-specific equipment and materials, applications of generic products, and novel systems developed at our facility reveal materials and systems which support optimal high-throughput microarray fabrication.

9:05 EZ-RAYS™: Activated Attachment Chemistry for Microarrays
Dr. Ezra S. Abrams, Program Leader, MicroArray Chemistry, Mosaic Technologies, Inc.
We will present data on the properties of EZ-RAYS™ slides, which feature a new immobilization chemistry for microarray generation. The active groups on EZ-RAYS™ slides are thiols, which are present on a proprietary, three-dimensional coating; the thiols form very stable covalent bonds with PCR products and with Acrydite modified oligonucleotides (100% retention of probe after 2 minutes at 100oC; 50% retention after 60 minutes). To demonstrate the sensitivity of EZ-RAYS™ slides, we use a spiking assay; target (rabbit reticulocyte cDNA labeled with Cy3dUTP) is spiked into carrier (Cy3 dUTP labeled cDNA from mouse polyA+ mRNA) and the mixture is hybridized to a slide with rabbit b-globin probes. Hybridization of globin cDNA, above background, is apparent when the globin is present at less than 0.005% (wt/wt) of total cDNA; this corresponds to about 5 transcripts/cell for typical mammalian cells.

9:35 Precision-Spotted, High-Quality Oligonucleotide and cDNA Microarrays Produced Using a Flexible Inkjet Platform
Dr. Paul Diehl Product Manager, Array Products, Agilent Technologies
A unique inkjet manufacturing process gives Agilent the capability to produce a variety of cDNA and oligonucleotide microarrays that best address the research needs of a particular project. Using a precision inkjet system, Agilent can spot picoliter volumes of cDNA or oligonucleotide solutions onto standard 1" x 3" glass slides. Using this approach, 2 arrays-each up to 14,000 features-can be made on one 1" x 3" glass slide. In addition to being extremely fast since the inkjet head can move rapidly over the printing surface without stopping or making contact with the print area, the spot shape uniformity produced by this process is more consistent than other currently available methods. A different variation of the inkjet approach gives Agilent the capability of actually synthesizing any number of oligonucleotide-up to 60 bases in length-right on the array surface. Since the manufacturing is completely software driven, this approach provides enormous flexibility to synthesize and array any combination of several thousand nucleotides. Using Agilent's dual-color laser, high-resolution Microarray Scanner, we have generated data showing the performance, consistency, and reliability of the inkjet arrays.

10:05 Poster and Exhibit Viewing, Refreshment Break

10:40 Standardizing DNA Arrays Using an Innovative Slide Concept
Dr. Wilhelm Plüster, Project Manager, Eppendorf AG
A new surface-activated slide developed by Eppendorf AG in conjunction with its partners enables the reproducible production of high-quality arrays by means of the spotting process and is therefore in a position to set a new quality standard. The heart of the Eppendorf Slide is an innovative surface-modification process that, due to the use of hydrophilic, three-dimensional surface structures, enables optimal density and accessibility of the reactive, functional groups for probe molecules. A previously unattained signal-to-noise ratio is achieved using this new surface chemistry together with the pioneering use of a special glass substrate. In summary, our slide concept consisting of a special glass substrate, an innovative surface-modification, fluorescence markers, and software is a significant milestone for the standardization of DNA arrays.

11:10 Using Photolabile 5'-O-phosphoramidites for the in Situ Synthesis of Inversely Oriented Oligonucleotides on Microarrays
Dr. Jörg Hoheisel
Photolabile 3'-O-[2-(2-nitrophenyl)propoxycarbonyl]-protected 5'-phosphoramidites were synthesized for an alternative mode of light-directed production of oligonucleotide arrays. Because of the characteristics of these monomeric building blocks, photolithographic in situ DNA-synthesis occurred in 5'-3' direction and conformed to the orientation of enzymatic synthesis, producing oligonucleotides that were attached to the surface via their 5'-end while the 3'-hydroxyl groups were available to enzymatic reactions such as primer extension by polymerases. Utilization of such microarrays will be shown.

11:40 Panel Discussion

12:10 Lunch (sponsored by Cambridge Healthtech Institute)

 

Microfabrication/Design

 

1:30 Chair's Remarks
Director of NEDO, MITI; and Professor of Physical Chemistry, Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Tokushima

Keynote Presentation
1:40 The Use of MAGIChips™ as an Array for Nanoliter Test Tubes for Parallel PCR Amplification of Different DNA and Other Procedures
Dr. Andrei Mirzabekov, Argonne National Laboratory
The use of MicroArray of Gel-Immobilized Compounds on chip (MAGIChip™) provides a higher quality and an increased sensitivity of analyses, as well as a possibility to carry out different chemical and enzymatic reactions within an individual microchip gel pad. In newly selected gels of the microchip, reactions can be carried out for long periods of time at high temperatures. This allows us to perform on-chip PCR amplification and other reactions with thermostable enzymes. Several successive enzymatic reactions are performed within the microchip gel pads. On-chip PCR amplification, allele-specific extension, single-base extension, ligation, and other reactions were carried out with the microchips either separately or in combinations. These on-chip reactions have been applied for identification of pathogenic viruses and bacteria and their drug-resistant mutations.

2:20 Applications of Microfluidic Laminar Flow Diffusion Structures in Drug Development
Dr. Bernhard H. Weigl, Manager, Business Development, and Senior Scientist, Micronics, Inc.
Micronics' proprietary diffusion-based separation and detection structures (H-Filters™ and T-Sensors™) are currently in development in a number of projects for upstream sample processing for HTS and PCR processes. New, exciting applications of this technology are in lead compound screening and in cell toxicity monitoring.

2:50 Micro- and Nanofabricated Chip Technology for Single DNA Molecule Analysis and Genomic Polymorphism Analysis
Dr. Yoshinobu Baba
Since human genome sequencing has been almost completed in 2000, the human genome project will quickly move on to the post genome sequencing era, including single nucleotide polymorphism (SNP) analysis, functional genomics, mutation analysis, transcriptome analysis, proteome analysis, and metabolome analysis. Capillary array electrophoresis plays a vital role in the genome sequencing era, but in the post human genome sequencing era, further development of analytical technology for DNA, mRNA, protein, and metabolites is highly required. We have been challenged to develop the novel technology for ultrafast DNA analysis by the microfabricated chip-based integration of all processes required for human genome analysis. I will describe our development for field-inversion electrophoresis on a chip for high-resolution separation of DNA, SSCP analysis on a chip for SNP analysis, a novel method for stretching the single DNA molecule on a chip for single molecule mapping, and novel technology for manipulation of single DNA molecule on a chip for single genomic DNA analysis. The possibility of development of nanochip technology will be discussed. I will also discuss the application of microscale technology to proteomics, including fast separation of proteins and peptides, cell-free amplification of proteins, and integrated microchip for protein analysis.

3:20 Poster and Exhibit Viewing, Refreshment Break

4:00 Gene Expression Microarray Design: From Concept to Product
Dr. Siqi Tan, Senior Scientist, Incyte Genomics, Inc.
The manufacture of high quality cDNA microarrays begins with a well-defined product design. The process of selecting genes, and the clones to represent them, involves many considerations. Selecting the appropriate clones from both Incyte and public clone sets is a critical step in producing useful cDNA based Microarrays. At Incyte, after reaching a consensus on the product specifications, a team of bioinformatics scientists nominates clones based on several predefined criteria. The overall gene representation on the microarray, the ability to choose clones from 3’ anchored gene bins, the range of sequence covered by particular clones, the sequencing direction of clones, the clones’ vector restrictions, and the availability of the clones as viable, verified reagents are all taken into consideration. Following the initial clone nomination, the candidate clones undergo a series of rigorous sequencing and bioinformatics verification processes to ascertain their identity and quality. Only clones that pass our strict nomination and the subsequent quality control standards are used to make Incyte’s 100% verified GEM™ Microarrays.

4:30 Tissue Microarrays for High-Throughput, in Vivo Gene and Protein Target Discovery, Validation, and Extension
Dr. Olli Kallioniemi, National Human Genome Research Institute, National Institutes of Health
Recent advances in molecular medicine have provided new opportunities to understand cellular and molecular mechanisms of disease and to select appropriate treatment regimens with the greatest likelihood of success. The clinical application of novel molecular, genetic, and genomic discoveries has been impeded by the slow and tedious process of evaluating biomarkers in large numbers of clinical specimens. DNA microarrays enable analysis of thousands of genes from one tissue specimen in a single experiment, whereas the tissue microarrays make it possible to analyze hundreds or thousands of tissue specimens in a single experiment using a single gene or protein probe. Together, the DNA and tissue microarray technologies will be very powerful for the rapid analysis of markers associated with disease prognosis or therapy outcome.

5:00 Millennium's Microarray Platform: Build Versus Buy Versus Integrate
Dr Gregory Kirk, Sr. Director of Technology, Millennium Pharmaceuticals, Inc
We will discuss how microarrays and other expression profiling platforms are used in our drug and marker discovery pipelines. This leads to a set of criteria for selecting a microarray platform: sensitivity/signal quality, gene content, throughput/efficiency and cost. We will describe how we evaluate these criteria and how this compelled us to developing our highly engineered nylon-membrane based platform using cDNA clone based elements. Details on assembling and validating large clonesets such as our 75,000 Human Complete Genome Set will be described as well as our high-throughput PCR, printing and hybridization systems. We will also outline the evolution of our reagent and image QC methods with an emphasis on automated materials tracking and image analysis tools. We will conclude with a brief discussion about future directions in non-cDNA based aray elements and mini-array strategies.

5:30 Panel Discussion

6:00 Close of Day One

 

Tuesday, April 24

DETECTION

 

8:00 am Poster and Exhibit Viewing and Light Continental Breakfast

8:30 Chair's Remarks
Dr. Steve Gullans, Associate Professor of Medicine, Harvard University

8:35 Alternatives to Fluorescence
Dr. Tom J. Whitaker, Chief Executive Officer, Atom Sciences, Inc.
Three alternative techniques for detection of hybridization on DNA arrays will be discussed. These techniques differ in their basic mechanism but share a common feature in that no label is required for the target DNA. One method measures the change in capacitance between the array surface and the hybridization solution as the hybrid forms. Another exploits the chemical difference between peptide nucleic acid probes and target DNA. The third technique uses a restriction enzyme to selectively remove a label on the probe if hybridization has not occurred. The relative merits, costs, and complexity of these techniques will be compared to conventional fluorescence techniques.

9:05 Quantum Interferometric Enhancement for Ultrasensitive Signal Detection in Biochip Microarrays
Dr. Sandeep Gulati, Research Scientist, ViaLogy Corporation
We will present a novel computational technique based on nonlinear quantum interferometry for the interpretation of DNA, RNA, and peptide nucleic acid-based microarrays. This presents an attempt to get an over 100- to a 10,000-fold improvement in detection sensitivity over classical state-of-the-art signal processing and bioinformatics techniques. This technique applies to the analysis of arrayed biomolecular, ionic, bioelectronic, biochemical, optoelectronic, radio frequency (RF), and electronic microdevices for genomics and diagnostics. Specifically, the technique enables mutation expression analysis at ultralow concentrations using high-density passive or active biochip microarrays, thereby significantly enhancing repeatability of measurements. Historically, interferometry has been used to measure very small differences in lengths, distances, and changes in dimension density and other properties by the interference of two waves of light for optical imaging and communication applications. In contradistinction ViaLogy is exploiting interference between a specific coding of post-hybridization biochip microarrays and target sequences of interest. Detection performance results comparing classical bioinformatics techniques and quantum interferometry will be presented.

9:35 A Novel, Sensitive Detection System for High-Density Microarrays Using Dendrimer Technology
Dr. Steve Gullans
High-throughput DNA microarray analysis requires detection of nucleic acid binding with high sensitivity and low background. We developed a dendrimer detection system that is simple to use and requires relatively little RNA. This technology can be adapted to multiple fluorophors facilitating detection of several samples on a single microarray.

10:05 Poster and Exhibit Viewing, Refreshment Break

10:45 Development of a Multilabel DNA Mapping Technique Using SERS Gene Probes
Dr. Tuan Vo-Dinh, Senior Scientist, Advanced Monitoring Development Group, Oak Ridge National Laboratory
We will describe the development of a multilabel DNA mapping technique using the surface-enhanced Raman scattering (SERS) method and instrumentation. The technology uses DNA gene probes based on SERS labels for gene detection and DNA mapping. The detection method uses nanostructured metallic substrates as SERS-active microarray platforms. The surface-enhanced Raman gene (SERGen) probes can be used to detect DNA targets via hybridization to DNA sequences complementary to these probes. The probes do not require the use of radioactive labels and have great potential to provide sensitivity, selectivity, and excellent label-multiplex capability. Advanced instrumental systems designed for spectral measurements and for multiarray imaging will be described. The usefulness of the SERGen approach and its applications in biomedical diagnostics and high-throughput analysis, as well as in DNA mapping and sequencing, will be discussed.

11:15 Rolling Circle Amplification Applications in Protein Arrays
Dr. Barry Schweitzer, Associate Director of Proteomics, Molecular Staging Corporation
Microarray-based mRNA expression profiling is a powerful functional genomics tool, but suffers from a major limitation of discordance with protein expression levels. Conventional approaches to protein measurements are either too expensive or lack throughput for simultaneous monitoring of expression levels of many proteins in parallel. Rolling Circle Amplification (RCA) is emerging as the signal amplification method of choice for DNA and RNA microarrays, since RCA uniquely allows target recognition, amplification, and detection in situ on the microarray. A recent adaptation of RCA, for the detection of antibody bound to antigen, termed immunoRCA, will be described. ImmunoRCA, represents a novel approach for signal amplification of protein-protein recognition events on microarrays. Clinical validation of this approach has been achieved by measuring allergen-specific IgE levels in hundreds of patients on microarrays and comparing these results to conventional immunoassays. Additional applications, involving ultrasensitive detection, will also be presented.

11:45 Panel Discussion

12:15 Luncheon workshop  sponsored by: Generating standardized microarray results: Using control reagents and software tools to normalize and validate your experiments Dr. Timothy Harkins, Product Manager, Amersham Pharmacia Biotech Dr. Hrissi Samartzidou, Senior Applications Scientist, Amersham Pharmacia Biotech. The advent of microarray technology has revolutionized gene expression analysis. However, comparison of gene expression data within and across microarray platforms has proven difficult, since there are few standard controls and a variety of normalization methods in use. In this technology workshop, we will introduce reagent and software solutions for standardization and validation of microarray data, including spot finding, data normalization and statistical interpretation. Such tools provide automated, accurate, and precise primary data extraction that enables quantitative comparison of data between experiments, users, and platforms. We will describe the use of these control reagents and software tools to produce standardized microarray data. In addition, we will describe a novel normalization method and present data to compare various normalization procedures.

 

Bioinformatics

 

1:30 Chair's Remarks
Dr. Inge Jonassen, Associate Professor, Department of Informatics, University of Bergen

1:40 Wavelet Decomposition Uncovers the Oscillatory Dynamics of Phenotype
Dr. Robert R. Klevecz, Research Scientist, Dynamics Group, Department of Biology, Beckman Research Institute of The City of Hope Medical Center
Wavelet decomposition and de-noising techniques, in combination with other signal and image processing methods, have been applied to expression microarray data to reveal that most yeast genes oscillate. This is true whether the genes are "cell cycle regulated" or not. While the original observations were made on synchronized cultures, temporally coherent expression is seen as well in yeast chemostat cultures that have not been synchronized. It therefore seems likely that some of what has been considered noise in expression microarray data is the gene signal being expressed with oscillatory dynamics. Given this, time series analyses provide a robust approach to uncovering the dynamics and connectivity relationships of gene expression in microarrays.

2:10 The Application of a Universal Platform-Independent Bioinformatics System for High-Throughput Data Analysis in Gene Expression Studies
Dr. Soheil Shams, President, BioDiscovery, Inc.
The first step in a microarray experiment involves the design and fabrication of an array. The bioinformatics aspect of this crucial step will be considered in detail. After the microarray hybridization experiment, an image of the array is obtained and analyzed in a highly accurate and unbiased manner by a walk-away technology from BioDiscovery. Expression parameters are computed, which describe the expression of each gene and provide statistical information about the quality of the data. Finally, to evaluate the behaviors of various genes, it is essential to mine the data, using various computational techniques, for verification of hypothesis or further explorations. The BioDiscovery system provides a universal, scalable, and platform-independent architecture that facilitates efficient microarray project management via a common interface linking the information used and produced at each stage of the project.

2:40 Untangling Microarray Signals
Dr. Inge Jonassen
In this presentation I will discuss different approaches to the analysis of microarray gene expression data. The focus will be on clustering and projection methods and illustrations will be given using the J-Express java application developed in our group. I will also briefly describe an approach developed to use microarray data together with genomic data to fully automatically discover putative gene regulatory signals. The approach is illustrated by a set of experiments on yeast S. Cerevisiae data. This work has been done in collaboration with groups at the European Bioinformatics Institute (UK) and at the University of Helsinki, Finland.

3:10 Poster and Exhibit Viewing, Refreshment Break

3:40 Integration of Microarray Information into a Bioinformatics Platform
Dr. David A. Nielsen, Senior Bioinformatics Specialist, InforMax, Inc.
Downstream of the microarrays, an automated high-throughput solution is required to store and process the massive volumes of information flowing in from these experiments. Efficient integration of microarray data with other genomic data types is required to identify the most promising targets. By combining enterprisewide distributed tools and databases with automated analysis protocols, large quantities of expression data can be examined in a 24 x 7 fashion.

4:10 Genomic Sensor Pads and Pattern Recognition: Impacting Both the Discovery and the Development of Drugs
Dr. Stephen Friend, President and Chief Executive Officer, Rosetta Inpharmatics, Inc.
Neither transcript levels nor protein levels directly define the functions of genes or the activities of compounds. By using the entire genome as a sensor pad either at a transcript level or at a protein level, it is possible using pattern matching to interpret unknown compounds and genes in terms of known references if coherent data sets are used. The focus will be on specific solutions to actual unmet needs in target identification, lead compound optimization, and safety and efficacy determininations required, shortening the overall drug discovery pipeline.

4:40 Panel Discussion

5:10 Reception (sponsored by Cambridge Healthtech Institute)

6:30 Close of Day Two

 

Wednesday, April 25

8:00 am Poster and Exhibit Viewing and Light Continental Breakfast

 

Applications

 

8:00 Chair's Remarks
Dr. Renae Lin Malek, Collaborative Investigator, Department of Functional Genomics, The Institute for Genomic Research

8:05 Microarrays: Application in the Drug Discovery Process
Dr. Steve M. Clark, GlaxoSmithKline Pharmaceuticals, Inc.
The advent of rapid DNA sequencing spawned the "genomic era," which introduced an exciting new dimension to the way biomedical research is conducted. In the very near future primary DNA sequence and gene map location will be available for ~100,000 human genes, and high-throughput technologies will be required to survey this genetic information on a comprehensive scale. DNA microarrays (also known as DNA chips) represent one example of a high-throughput technology designed to study RNA expression in cells and tissues (e.g., normal and diseased) of tens of thousands of genes simultaneously. Briefly, a glass microscope slide is robotically spotted with ~10,000 cDNAs encoding full or partial gene fragments, and the slide is incubated with fluorescently labeled cDNA made from RNA isolated from cells or tissues. A confocal scanner is used to detect labeled cDNA hybridized to complementary DNA sequences on the chip. Fluorescent signal intensity represents relative expression of the corresponding genes when compared to their expression pattern in a control sample. As part of a team effort, scientists at SmithKline Beecham developed a robust cDNA-based microarray platform and have validated the technology as a powerful tool for surveying RNA expression in human, yeast, and bacterial systems.

8:35 Corning's microarray manufacturing technology results in high quality differential gene expression profiles in HL-60 cells induced to differentiate with retinoic acid.
Dr Debra Hoover, CMT Application Scientist, Corning Incorporated
Corning has developed a parallel printing technology that enables printing of 10,000 human genes per slide, per minute. Corning's arrays have a dynamic range greater than two orders of magnitude yielding highly reproducible data (CV < 25%). Here we introduce Corning's innovative printing process and demonstrate the quality of array data obtained from Corning's Human 10K Arrays. Differential gene expression of human hematopoietic cells (HL-60) induced to differentiate with retinoic acid will be presented.

9:05 Synthetic evolution using arrays
Dr. Glen Evans, President and Chief Executive Officer, Egea Biosciences, Inc
The human genome project has amassed a vast array of DNA sequence information that potentially makes possible the development of new, customized proteins, metabolic pathways and networks. We have developed a novel techology for the direct chemical synthesis and assembly of genes from csequence databases. This approach enables the production of large protein variant array libraries and targeted development of customized enzymes and biomaterials. This technology is being applied to a number of problems in agriculture, industrial processing and medicine.

9:35 Poster and Exhibit Viewing, Refreshment Break

10:15 In Vitro, Microscale Metabolic Engineering as a Tool for New Compound and New Process Discovery
Dr. Jonathan S. Dordick, Howard P. Isermann Professor and Chair, Department of Chemical Engineering, Rensselaer Polytechnic Institute
We are addressing the critical topic of functional genomics in general and the specific application of metabolic pathway engineering by fabricating multi-enzyme-containing microchips. Enzymes and the metabolic pathways which they comprise can be manipulated to yield a range of novel products. This is critical to accelerate the synthesis of new compounds for use in biotechnology, industrial chemistry, pharmaceuticals, and agrochemicals. We have used this approach to generate a variety of polymeric materials on the microchip format, including phenolic oligomers for use as selective enzyme inhibitors and polyhydroxyalkanoate derivatives for use as biomaterials.

10:45 Expression Profiling Src Mutants Using cDNA Microarrays
Dr. Renae Lin Malek
We examined the gene expression patterns of rat fibroblasts transfected with Src mutant and wild-type constructs to catalog transcriptional changes related to constitutive Src expression. Data analysis revealed gene expression patterns correlating with the acquisition of a transformed phenotype.

11:15 Genome-Derived Microarrays of Human Open Reading Frames
Dr. David Hanzel, Principal Scientist, Amersham Pharmacia Biotech
In order to quantify the gene density of the human genome we have subjected completed sequence to systematic search for Open Reading Frames (ORF) and assessment of gene expression. While the computational prediction of genes in genomic sequence can provide a prediction of total gene number, the measurement of specific message is an essential confirmation. The combination of raw genomic sequence, predictive algorithms, and gene-expression microarrays is a powerful tool to find and confirm the existence of novel genes.

11:45 Panel Discussion

12:15 Lunch (on your own)

 

Proteins

 

1:30 Chair's Remarks
Dr. Michael Cardone, Department of Biology, Massachusetts Institute of Technology

1:40 Protein Biochips as Tools for Discovery and Target Validation
Dr. Brent L. Kreider, Vice President of Biological Research, Phylos, Inc.
This presentation will describe the creation of high-affinity antibody mimics and their use for the production of protein affinity chips. These chips will be designed to profile the protein content of most any biological sample both qualitatively and quantitatively. Such tools will be invaluable across discovery, target validation, and diagnostics.

2:10 Protein Biochips as New Tools in Proteomics
Dr. Steffen Nock, Director of Biochemistry, Zyomyx, Inc.
Novel high-throughput biological applications in the drug discovery process, disease diagnosis, and the development and application of patient-specific medicines require highly parallel, miniaturized device technology applied to proteins and their biochemical pathways. While technological innovation has adapted the analysis of genetic material to a miniaturized format, the more delicate nature of protein structures has precluded the development of analogous devices for proteins. Protein biochips have started to emerge recently based on new developments and integration efforts in advanced materials, protein engineering, and detection physics. Recent developments and selected examples will be presented with an emphasis on the technical challenges in surface and assay methodologies.

2:40 Extending Microarray Technology to Study Protein Function
Dr. Gavin MacBeath, Associate Professor, Harvard University
As more and more DNA sequence information becomes available, we are left with the exciting but formidable task of deciphering protein function. Our laboratory has approached this problem from two directions. First, we have developed microarray-based methods that enable the rapid and parallel screening of small molecule libraries to identify new ligands for selected proteins. Such compounds, which may either induce or inhibit their target proteins, can then serve as powerful tools to dissect protein function in vivo. Secondly, we have recently developed methods to array purified proteins at extremely high spatial densities on glass slides in such a way that their folded conformations are preserved. These arrays enable us to screen rapidly for protein-protein interactions, enzyme-substrate interactions, and protein-small molecule interactions. As a further application of this work, we are currently developing antibody arrays to address the difficult problem of quantifying protein abundance, modification, and localization in biological samples.

3:10 Poster and Exhibit Viewing, Refreshment Break

3:40 ProteinChip Technology Enabling Novel Biomarkers
Dr. Anju Dang, Applications Scientist, Ciphergen Biosystems, Inc.
Our ProteinChip technology is becoming mainstream in major therapeutic, academic, and clinical research settings. This technology is enabling benchtop proteomics discoveries including new novel biomarkers (examples: prostate cancer, Alzheimer's disease, toxicological protein markers, and more). All of these findings are helping scientists to answer questions on a "protein level" (what is really happening) so that they can move on to their next stage of experimentation faster than ever before.

4:10 Affinity Capture by Proteins Arrayed on MALDI and Glass Surfaces
Dr. Michael Cardone
We have used single-chain and conventional antibodies and non-antibody proteins as affinity reagents coupled to glass surfaces and to MALDI mass spectrometry surfaces. With this we detect and identify ligands from fractionated cell extracts. Our arrays are focussed to look at proteins in well-characterized cell signaling pathways. We are also using these technologies to screen small molecules for their ability to interfere with defined protein-protein or protein-peptide interaction.

4:40 Peptide, Protein, and Antibody Arrays as an Integrated Approach to Following Human Tissues in Health and Disease
Dr. Ian Humphery-Smith, Chief Operating Officer, Glaucus Proteomics B.V.
Glaucus Proteomics has developed a molecularly sound and fully scalable approach to the task of undertaking meaningful high-throughput and reproducible analyses of the human proteome in health and disease. This will facilitate large sample cohorts accompanied by high levels of proteomic coverage beyond that possible by traditional technologies. Analysis of the simplest living organisms (Mycoplasmas) over the last decade and currently the publication of the most complete proteome have taught us that "traditional proteomics" (2-D gels, advanced image analysis, and mass spectrometry) is totally inadequate for a major push on the human proteome. Thus, our integrated approach links parallel generation and screening of antibodies, molecular expression vectors for immobilization and immunization, extreme high-throughput screening engines, "genomewide" triple protein enrichment including "on-array" final purification, proprietary surface chemistries critical to effective HTS Western Blotting, and peptide-based "proteomic closure" strategies to allow screening of the "near-to total" proteome in living tissues. Complementary biocomputing activities are focused on the development of dynamic data extraction tools designed to highlight biologically relevant permutations and combinations from within multivector data sets.

5:10 Panel Discussion

5:40 Close of Conference

Sunday, April 22

5:00-7:00pm Early Registration and Poster and Exhibit Setup

PRECONFERENCE WORKSHOP 11:30 am Workshop Registration 12:00-5:00 Getting Grounded in Microarray Informatics: Leading Challenges, Approaches, and Software Solutions Dr. Nathan Goodman, Senior Vice President, 3rd Millennium, Inc. Dr. Eric Neumann, Vice President of Life Sciences Informatics, 3rd Millennium, Inc. Presenting the nuts-and-bolts of microarray informatics, this special seminar is based on proprietary research and is led by two bioinformaticians with over 15 combined years of experience in this field. The seminar is ideal for those scaling up their projects or anyone newly entering this field. Tune in to our Free Internet-Accessible Workshop Preview Event. Contact Andrew Branca, Vice President, Business Development & Online Services, at 617-630-1375 or abranca@healthtech.com, or point your browser to: http://www.geneed.com/chi Corporate Sponsor Biographies Amersham Pharmacia Biotech (APBiotech), the life sciense business of Nycomed Amersham plc, is a leading provider of biotechnology sytems, products and services for research into genes and proteins, for the discovery and development of drugs and for the manufacture of biopharmaceuticals. The customers for APBiotech's products and technology are pharmaceuticals and biotechnology companies and leading research and academic institutions in North America, Europe, Latin America and Asia. For more information about APBiotech, Please visit our web site at www.apbiotech.com. Rosetta Inpharmatics' technologies and services permit researchers to fully explore the diverse causes and consequences of changes in gene expression, and to focus on those cellular processes that are specifically affected by exposure to pharmaceuticals, chemicals, or genetic engineering. The Company's integrated platform comprises design and analysis of proprietary DNA microarrays, a powerful, flexible informatics system, and advanced molecular biology techniques to support the expression profiling programs of pharmaceutical, biotechnology, agrochemical, and ag-biotech companies. The Rosetta platform is economical, reliable, and flexible - ideally suited to meet today's target, pathway, drug, and agrochemical discovery needs. Back to the top of the page

Hotel Information
Seaport Hotel
One Seaport Lane
Boston, MA 02210
T: 617-385-4000
F: 617-385-4001
Room Rates: $159/S o $184/D
Cut-off Date: March 30, 2001
Please call the hotel directly to make your room reservation. Identify yourself as a Cambridge Healthtech Institute conference attendee to receive the reduced room rate. Reservations made after the cut-off date or after the group room block has been filled (whichever comes first) will be accepted on a space-and-rate-availability basis. Rooms are limited, so please book early.

Travel Information
Special Airline Discounts Available
Special zone and discount fares have been established on United Airlines for this conference. Please call Great International and National Travel at 617-527-0800 and ask for Joyce Dunn or e-mail her at jdunn@greatintltravel.com. Or you may call United Airlines Meeting Reservations Center directly at 1-800-521-4041. You should reference ID #579YS.

Call for Posters
Cambridge Healthtech Institute encourages attendees to gain further exposure by presenting their work in the poster sessions. Please fill out the registration form, with the poster title and primary author. To ensure inclusion in the conference binder, a one-page summary must be submitted and registration must be paid in full by March 23, 2001. POSTER INSTRUCTIONS

Call for Exhibitors
Last year we saw the exhibit hall sell out quickly and watched as our exhibitors successfully meet with over 350 delegates. This year we have prepared space for 32 booths and we expect to have an attendance of well over 500 of the leaders in genomic research. As of January 2, 2001, the following companies have secured their participation:

Amersham Pharmacia Biotech
Informax, Inc.
Mergen Ltd.
MWG-Biotech, Inc.
Operon Technologies, Inc.
Protogene Laboratories
Qiagen, Inc.
Rosetta Inpharmatics
Xenopore Corp.
Whatman Bioscience

If you are interested in reserving a booth or in receiving a complete exhibitor prospectus please contact Mary Cushman at 617-630-1380.