CHI's Protein to Profits - Proteomics Europe

Proteomics is the new "omics" on the block. This conference is designed to showcase protein-protein interactions, protein array production, protein profiling, and the resulting potential of protein research for drug discovery. Rarely acknowledged, economics is an important aspect of the "omics" family as well. Although proteomics does remain hypothesis-driven, advances in technologies such as chips, arrays, and informatics mean this burgeoning enterprise has the potential application to turn "omics" from red into green. CHI's Proteins to Profits is designed to provide information in a precise, productive manner. Plan to attend Proteomics-Europe and Protein and Peptide Arrays to view the entire picture of the new "omics."

Scientific Advisors
Dr. Robert B. Russell, European Molecular Biology Laboratory (EMBL)
Dr. Donny Strosberg, Hybrigenics SA

Speakers
Dr. Michael R. Alvers, DEFiNiENS AG
Dr. Julio E. Celis, Danish Cancer Society and Danish Centre for Human Genome Research
Dr. Mary E. Donlan, Accelrys
Dr. Michael Egholm, Molecular Staging, Inc.
Dr. Dominik Escher, ESBATech AG
Dr. Anne-Claude Gavin, Cellzome UK
Dr. Stefan W. Henning, Xerion Pharmaceuticals AG
Dr. Juan J. Herrero, AxCell Biosciences Corporation
Dr. Pierre Legrain, Hybrigenics SA
Dr. Matthias Mann, MDS Proteomics
Dr. Steven Pelech, Kinexus Bioinformatics Corp.
Dr. Keith Rose, GeneProt Inc.
Dr. Robert B. Russell, European Molecular Biology Laboratory (EMBL)
Dr. Walter Schubert, MelTec GmbH
Dr. Mathias Uhlén, Royal Institute of Technology and Affibody AB

Protein-Protein Interactions
Protein Specificity
Target Validation
High-Throughput Analysis
High-Throughput Proteomics

Protein Profiling (Informatics)
ProteomWeaver
Protein Profiling Technologies with Immunohistochemistry
PepSea Technology
High-Throughput Proteomics
Mapping Protein Phosphorylation Networks

Proteomics in Drug Discovery
Target Discovery in Silico
CALI
Antibodies for Target Validation
Topological Proteomics

7.30 Registration, Poster and Exhibit Viewing, and Light Continental Breakfast

8.30 Chair's Opening Remarks
Dr. Pierre Legrain, Vice President Science & Technologies, Hybrigenics SA

8.40 Keynote Address
Proteomics Moves to the Industrial Scale
Dr. Keith Rose, Chief Scientific Officer, GeneProt Inc.
With the Human Genome Project and a private initiative, genomics moved to the industrial scale and led more rapidly than most people had imagined to a landmark for mankind, the determination of the human genome. Proteomics, the study of the proteins present in cells, tissues, or biofluids, is now moving to an industrial scale. The scientific challenge is even greater, but so should be the rewards.

9.15 Protein Sequences, Structures, Specificities, and Interactions
Dr. Robert B. Russell, Group Leader, Structural Bioinformatics, European Molecular Biology Laboratory (EMBL)
Proteins almost invariably belong to homologous families. Although proteins in the same family usually show some degree of functional similarity, there are important differences that dictate details regarding specificity. This talk will describe some current approaches for using protein sequence and structure data to analyze and predict details of protein specificity for "orphan" sequences, for which functional details can only be inferred by homology.

9.45 Protein Interaction Mapping for Target Validation
Dr. Pierre Legrain
Hybrigenics identifies and validates therapeutic targets to improve the efficiency of the drug discovery process. The company's approach is based on (1) a high-throughput protein interaction mapping technology to unravel the role of proteins in functional pathways, (2) a computer-aided expert analysis platform to prioritize prevalidated therapeutic targets, and (3) unique cellular assays to validate the target's functional role, using the domains involved in the interacting proteins.

11.00 High-throughput protein interaction analysis
Dr. Juan J. Herrero, Director of Screening, AxCell Biosciences Corporation
While proteomics is defined as a comprehensive study of proteins expressed by an organism, it is often limited to expression profiling and sequence analysis. In reality, of course, proteins are not important simply because they are present but because they have unique functions. Most proteins function at least partly through their interactions with other proteins, and this information is not apparent from 2D PAGE expression analysis or amino acid sequencing. A comprehensive analysis of protein interactions is thus critical to proteomics as functional analysis cannot otherwise be considered complete. Protein interactions may be studied via expression in yeast two-hybrid complementation systems. But the tremendous quantity of data necessary for comprehensive analysis requires utilization of modern automated sample-handling instrumentation and data-handling software. AxCell Biosciences has developed true high-throughput, in vitro protein interaction analysis. This process involves highly parallel peptide synthesis and protein expression, as well as custom HTS solutions. With InforMax, AxCell is also developing sophisticated tools for facile visualization and experimental manipulation of the complex patterns and pathways of protein interaction important for intracellular signaling processes.

11.30 High-Throughput Proteomics
Dr. Mathias Uhlen, Professor, Biotechnology KTH, Royal Institute of Technology and Chairman, Board of Directors, Affibody AB
A bioinformatic approach was used to identify all putative genes from human chromosome 21, and almost all of them have been expressed in a semi-automated process. The resulting proteins and peptides were used to create antibody reagents. Labeled antibodies have been used to carry out functional proteomic studies, with particular emphasis on expression localization. The use of tissue arrays has facilitated the throughput of these studies. Comparisons of protein expression results with gene expression data will also be discussed.

13.30 Chair's Remarks
Dr. Julio E. Celis, Scientific Director, Danish Cancer Society and Danish Centre for Human Genome Research

13.35 ProteomWeaver: A New Software for High-Throughput 2D Gel Image Analysis
Dr. Michael R. Alvers, Director, Bioinformatics, DEFiNiENS AG
For proteomic studies, 2D gel electrophoresis has become an extremely powerful tool to highly resolve thousands of differentially expressed proteins within a cell. For comparing a high number of groups of 2D gels, highly specialized software tools have become necessary. The automation of these software tools has become one of the primary bottlenecks of proteomics. In this context, we have developed a new 2D gel image analysis software for high-throughput gel analysis. ProteomeWeaver uses highly improved spot detection, spot quantification, and image-warping algorithms compared to existing image software analysis tools being up to 90% faster compared with conventional systems.

14.05 Proteomics and Immunohistochemistry Reveal Tumor Heterogeneity among Urothelial Papillomas
Dr. Julio E. Celis
In our laboratory we are applying protein-profiling technologies in combination with immunohistochemistry to reveal bladder cancer heterogeneity with the long-term aim of predicting the biological behavior of these lesions in terms of recurrence and progression. Here I will report on our strategy to identify tumor heterogeneity within urothelial papillomas diagnosed as having the same stage and grade of atypia.

14.35 The Large-scale Study of Protein Complexes for Target Validation
Dr. Anne-Claude Gavin, Cellzome UK
To date scientists have studied proteins largely as discrete entities, yet most proteins operate collectively as part of protein complexes or pathways. A deeper understanding of protein interactions will assist in validating novel drug targets and may extend the usefulness of existing drug targets. At Cellzome we have implemented a high-throughput use of Tandem Affinity Purification (TAP) for effective isolation of complexes involved in human disease that is very robust, and is providing novel insights into cellular pathways.

15.45 Proteomics Technology for Easier Mining of Novel Genes and Expressed Proteins
Dr. Matthias Mann, Chief Proteomics Officer, MDS Proteomics
Unraveling the mystery of protein activity is one of the largest challenges in scientific research and a key driver in the development of tools that enable the quick identification of high-quality targets. Current proteomics technologies can only identify already known proteins or proteins predicted from genomic data. MDS Proteomics uses PepSea to go one step beyond, enabling the identification of unknown proteins with no prediction necessary. PepSea also can, in seconds, determine the location and identity of human genes that encode the proteins. Because of the error tolerance inherent in the PepSea algorithm, proteins can even be identified regardless of intervening sequences, which make up the majority of human DNA.

16.15 Antibody-Based Cell Signaling Proteomics - Mapping Protein Phosphorylation Networks
Dr. Steven Pelech, President & Chief Executive Officer, Kinexus Bioinformatics Corporation
Using an antibody-based detection system that is proprietary to Kinexus called Kinetworks™, over 100 proteins can be selectively tracked on a single SDS-PAGE minigel with 250 µg of crude protein extract. Kinexus has developed several commercial screens for the specific analysis of panels of protein kinases, protein phosphatases, phosphoproteins, cell cycle proteins, heat shock/stress proteins and apoptosis proteins. Many of these regulatory proteins are produced at low levels that they not detected by traditional 2D gel-based approaches. We have observed profound differences in the expression, phosphorylation states and subcellular locations of these regulatory proteins in hormone-, drug- and toxin-treated cultured cells and in tissue biopsies from animal and human patient samples. This information is being used to map novel cell signalling pathways through bioinformatic analyses.

Proteomics in Drug Discovery
Registrants of Protein and Peptide Arrays are welcome to attend the Tuseday morning session of
Proteomics-Europe at no extra cost.

8.30 Chair's Remarks
Dr. Ian Humphery-Smith, Department of Pharmaceutical Proteomics, University of Utrecht; and Glaucus Proteomics B.V.

8.35 Keynote Presentation
Human Protein Arrays and Their Applications
Dr. Ian Humphery-Smith
The use of protein arrays to dissect the immune response in mice following parallel immunization with 100 recombinant human antigens is highlighted in this keynote presentation.

9.15 Target Discovery in Silico: Combining Genomic and Proteomic Data
Dr. Mary E. Donlan, Director, European Life Science Marketing, Simulations and Modeling Product Division, Accelrys
With the vast amounts of data coming out of the Human Genome Project and other sequencing efforts, researchers are faced with the challenge of extracting the important drug targets from all of these data. I will describe a method that combines 3D structure-based methods with traditional bioinformatics methods to enrich the level of functional assignment for a set of sequences. These methods have been implemented in an automated pipeline for high-throughput annotation. Application of this technology to the human genome will be described.

9.45 Use of Protein Profiling For Discovery Of Clinical Trial Biomarkers And Drug Targets
Dr. Michael Egholm, Vice President of Research, Molecular Staging, Inc.
Molecular Staging is using chip-based, high-throughput, protein profiling for drug discovery proteomics. We have developed a protein chip that measures 120 human growth factors, cytokines, chemokines, soluble receptors, and inducers/suppressors of apoptosis with ~10pg/ml sensitivity. When allied with multivariate bioinformatic analysis tools, protein profiling of large numbers of serum, plasma or tissue culture supernatents offers a powerful, new approach to drug target discovery, identification of biomarkers for prediction or assessment of drug response, and molecular staging, classification and subtyping of disease. Examples of the power of drug discovery proteomics in human diseases, such as cerebral palsy and severe combined immunodeficiency, and in lead compound selection will be presented.

11.00 CALI: A Highly Efficient Tool for Protein Target Validation
Dr. Stefan W. Henning, Director of Functional Biology, Xerion Pharmaceuticals AG
With the completion of the Human Genome Project it has become apparent that the gene-to-drug paradigm will fall short on its promise to deliver new therapeutics for human disease. This shortfall can largely be blamed on the difficulties in deciphering the function of proteins, which represent more than 90% of today's drug targets, from plain nucleotide sequence. The key to future effective and rational drug development is the identification of disease-relevant protein targets and understanding the relation between their function and structure. Chromophore-assisted laser inactivation (CALI) can specifically inactivate protein function by targeted induction of photochemical modifications at functional sites of the protein. The implementation of process automation, combined with the use of target-specific scFv antibodies selected by phage display technologies, has transformed CALI from an academic tool to an industrial-scale protein target validation technology that provides rapid information about protein function in a cellular process or a diseased state.

11.30 Antibodies for Target Validation
Dr. Dominik Escher, Chief Executive Officer, ESBATech AG
Applications of single-chain antibodies within the cell have great promise, both in target validation and therapeutics. Unfortunately, the intracellular environment differs from the natural secretion pathway of antibodies. Within the cell, the reducing environment prevents formation of disulfide bonds that are known to be important for the stability, the correct folding, and therefore the function of the majority of single-chain antibodies. Thus, most of the tested single-chain antibodies have a reduced affinity to their target or are even completely not functional within the cell. We have developed a novel in vivo technology that identifies single-chain antibodies suitable for intracellular applications. Based on these selected single-chain antibodies, in vivo screenings are performed to identify new antibodies directed against cytoplasmic and nuclear targets. Subsequently, these single-chain antibodies are expressed in the cell system or model organism to validate the target.

12.00 Topological Proteomics: Protein Networks and Cellular Function - Optimizing Target Selection
Dr. Walter Schubert, Chief Executive Officer, MelTec GmbH
At the current stage of the life sciences industry, those companies with more efficient technologies for turning genomics and proteomics information into drug discovery programs will be the most successful companies. The number of new potential drug targets is overwhelming drug developers who need appropriate tools to better lead compounds for development. Efficient target validation will become a key driver of success.MelTec has developed a whole-cell protein fingerprinting technology capable of gathering the topological proteomics information of intact cells in their natural environment in tissues; visualizing protein networks and correlating them with cellular function. This accelerate and enhance the drug target and lead compound selection and validation processes.

13.00- Registration for Protein and Peptide Arrays:
Pitfalls, Prospects, and Promise

Hotel Information
Arabella Sheraton Grand Hotel
Arabellastraße 6
Munich D-81925, Germany
T: 49-89-9264-0, F: 49-89-9264-8699
Room Reservations:
T: 49-89-9264-8521 o F:49-89-9264-8509
Room Rates:
163.00 Euro/single, 178.00 Euro/double
Cut-off Date: March 1, 2002
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.