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HUPO, Opening Its Umbrella, Reports Progress on Initiatives, Adds Education

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The Human Proteome Organization revealed itself as more of an umbrella group than a central organizer in the latest progress report delivered earlier this month at a two-day forum during Cambridge Health Institute’s PepTalk conference in San Diego.

The projects that HUPO is embracing include an antibody initiative, a plasma protein project, a liver proteome project, a protein standards initiative, and an education and training initiative, which is still at its planning stage. Most of these projects will be organized at the local or national level, yet will have international participants.

A prime example of this federated structure is the antibody initiative of the German Society for Proteome Research, called European Proteomics Initiative, which Marius Ueffing from the GSF Research Center for Environment and Health in Neuherberg, Germany, discussed at the forum. This initiative aims to establish a European protein and antibody bank with the goal of generating monoclonal antibodies against subsets of recombinant human proteins. The reason for choosing monoclonal antibodies, Ueffing said, is that the technology is well-established and free of intellectual property, unlike, for example, phage display technology.

The production end of the initiative will be an international collaboration: Various German research centers will provide full-length cDNA and high- throughput protein expression, and Ueffing mentioned that the initiative currently favors a cell-free protein expression system developed by Roche. For the production of the antibodies, however, two centers in Tartu, Estonia, and Rijeka, Croatia, are currently under consideration, largely for their existing infrastructure and low production costs. An independent center will evaluate the antibodies for their function, after which the production centers will maintain the hybridomas and provide them to academic and industry researchers. A database and central repository will be established as well.

According to Ueffing, antibodies to proteins from the central nervous system will likely be chosen as a pilot project. Other potential subsets are antibodies to blood or serum proteins, as well as liver proteins. According to the organizers’ estimates, the pilot study will cost about €15 million. The initiative is planning to raise €7 million from industry, and already has a commitment for €3 million, tied to certain conditions, from an undisclosed company, Ueffing said. In the past, Roche has said that it would consider contributing to an antibody initiative.

The initiative is also hoping to obtain €8 million from the European Union’s 6th Framework Program, a large science funding initiative, and will submit an application this fall. If the EU funding does not come through, though, the project can still go ahead on a smaller scale but would be geared more towards pharma’s and biotech’s interests, Ueffing told ProteoMonitor.

In return for financial contributions, companies will get license-free access to the antibody bank, obtain antibodies at production cost, and have access to cDNAs, clones, cell lines, and know-how. Although the antibodies themselves would be free of intelletual property, users would be able to create IP for applications using the antibodies, Ueffing said. The initiative aims to collect €4 million for pharmaceutical and diagnostic use of the antibodies, €2 million for diagnostic use only, and €1 million for their use in research products. Academic researchers will obtain free access to the resource.

The initiative’s first project will be a feasibility study, estimated at €5 million, the goal of which is to create 1,000 proteins against CNS proteins by 2007. The initiative wants to raise €2.5 million by early next year and establish production in 2004.

The initiative’s supervising board includes Sam Hanash, president of HUPO; Matthias Mann, who formally heads the HUPO antibody initiative; and Wolfgang Mutter, head of global marketing at Roche Diganostics.

A workshop to discuss further details and attract more industry participants is planned for mid-May 2003 in Frankfurt.

Next-Generation Proteomics

HUPO also unveiled plans to focus on education and training, with Hanash revealing ideas for the developing project. This education initiative, which was suggested as a potential HUPO activity by several participants of the HUPO Versailles Congress last November, will be chaired by Peter James at Lund University in Sweden. According to Hanash, HUPO is planning a web-based proteomics portal that will provide overview articles and important proteomics papers. The organization also plans to develop course material for an MSc-level degree that will be complemented by lab-based courses in different countries. According to Hanash, several laboratories have already expressed interest in organizing and hosting one- or two-day courses. HUPO, he said, would like to partner with a publishing group to print a text book and provide the web portal. National proteome organizations, he added, could be engaged in translating and teaching the course material in the languages of their respective countries. HUPO will be seeking funding for the project from government and other funding agencies.

Plasma, Liver, Brain, and Brawn?

Gilbert Omenn from the University of Michigan gave an update on HUPO’s plasma proteome project (see ProteoMonitor 11-18-02), the initial aim of which is to catalog all the proteins found in human plasma. In a pilot phase, which is to start soon and will be administered at the University of Michigan, participating laboratories will analyze a plasma sample provided by HUPO using their method of choice. According to Omenn, HUPO has several sources of serum and plasma available for the pilot study: Citrated plasma samples from the American Red Cross, serum and plasma samples collected in collaboration with BD Biosciences, as well as freeze-dried plasma samples from the National Institute for Biological Standards and Control, based in South Mimms, UK. These freeze-dried samples would be easier to ship, especially between countries, Omenn pointed out. In addition, the Chinese Academy of Medical Sciences has offered plasma samples collected at hospitals, which could be distributed to laboratories in Asia and Oceania that participate in the pilot study. A database to store the results from the pilot project is currently in the planning stage. The first results will be presented at HUPO’s next annual congress in the fall and are to be published in a special issue of Proteomics, Omenn said. The list of participating non-commercial laboratories has grown to about 30, roughly half of which are located in the US. Moreover, about 30 companies have expressed interest in participating in the research, or contributing in other ways, such as by providing equipment.

The liver proteome initiative is largely driven by funding from the Chinese government, which “has made a commitment to invest tens of millions of dollars into this project,” according to Hanash.

Several other “model proteomes” are in the planning phase. Hanash mentioned a possible brain proteome initiative, which might arise from a human brain proteome project currently ongoing in Germany (see ProteoMonitor 2-11-02). Furthermore, NIMH and NIDA are planning to hold a workshop on “Model systems for neuroproteomics” on March 3 and 4, Hanash said, following up on the neuroproteomics workshop organized by NINDS last December (see ProteoMonitor 12-16-02). Moreover, the French Muscular Dystrophy Association, which has been supporting genomics projects in France, has expressed an interest in devoting resources to a muscle proteome project, Hanash said, and a workshop is planned for the summer.

Finally, Henning Hermjakob, Swiss-Prot applications coordinator at the European Bioinformatics Institute, talked about the current status of the Proteomics Standards Initiative (PSI), which is aiming to establish standards for mass spectrometry and protein-protein interaction data. The initiative may start collaborating with Eurospec, an EU-funded mass spectra archive that is slated to launch this spring, he said. For protein interaction data, a “level 1” standard to capture basic data should be available by this April, he added. An XML schema version 0.1 is already finished and currently under discussion. PSI held its second meeting on January 22-24 at the EBI in Hinxton, UK.

HUPO’s second annual congress will take place October 8-11, 2003, in Montreal, Canada.

— JK

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