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 | | | | Mar 10, 2010 - 11:55 PM | |  |  | |  | | 680 Reads | comments?   |
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| HLPP satellite meetings at HUPO conference in Beijing, October 2004 |  Our next opportunity for discussion and development is coming up fast now! The HUPO World Congress 2004 takes place in Beijing, October 25-27, 2004. Prior to the Congress, on October 23-24, there are satellite meetings of the HUPO working groups, one of them is the Human Liver Proteome Project (HLPP).
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| Action Plan: NIH-funding support for HLPP |  Liver disease is an important cause of morbidity and mortality in the United States, affecting persons of all ages, but most frequently individuals in the productive years of life, between the ages of 40 and 60 years. A human proteome initiative would allow the rapid translation of findings from basic research to practical means of prevention, control and cure of liver diseases. To date approximately 15 M USD has been secured for the initial phase of HLPP ($10M from Chinese Government, $2.5M from Genome Canada, $2M from INSERM and ARC). It is therefore timely to consider a US participation in this effort and to provide input in the development of an action plan for the HLPP. To assure the success of the project, NIH should contribute to this effort, using various mechanisms and sources of support for research and for enhancing cooperation and coordination. HLPP is a large-scale biology project that is suited for a trans-NIH initiative. NIDDK is developing an Action Plan for Research in Liver Disease to address the burden of liver diseases in the United States. The Action Plan will address the broad range of liver disease research, and will help guide NIH initiatives in liver disease research. The HLPP initiative goes beyond a single Institute‘s interest and is also part of the priorities for: NCI (increasing incidence of HCC); NIAID (HCV is the most common chronic blood-borne infection in the US); NIAAA (alcohol-related liver disease and interactions between alcohol and HCV in cirrhosis and HCC); NIDA (hepatitis C, interactions between HIV and HCV, HIV and HBV); NIEHS (hepatotoxicity); as well as NIST (data interopearability in large scale projects) and the FDA (drug toxicity). Therefore, a recommendation for providing funding to accomplish the objectives of the HLPP would be through a trans-Institute RFA. A trans-Institute commitment would make available sufficient funds for the RFA, avoid duplication of efforts, permit cross-fertilization, assemble relevant expertise. This mechanism will enable researchers working in liver proteomics to submit at the same time for review by an assembled panel with expertise in proteomics, proposals to accomplish objectives as defined in the RFA. NIH should also ensure that the resulting research effort is a united one and not a loose collection of individual R01 grants without integration. A cooperative agreement mechanism with oversight by NIH and regular meetings to foster exchange is necessary. Funding for a centralized resource center (tissue collection, proteomic platforms, data analysis) may assure that the start of the pilot phase is not delayed.
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| Action Plan: Building bridges with the HUPO Plasma Proteome Project (PPP) | The scientific objectives of this effort to build bridges between the plasma and the liver proteome projects are:
(1) To determine which proteins in plasma are synthesized in the liver
(2) To determine the dynamic of the changes affecting these proteins in diseases of the liver
(3) To determine the dynamic of the changes affecting these proteins in diseases in other organs
(4) To determine the dynamic of the changes affecting these proteins as indicators of hepatotoxicity
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| Action Plan: Data capture, analysis and sharing | The power of this initiative will stem from the integrative analysis of experimental data from a large number of laboratories. Participating organizations will apply their expertise and key technologies to common sample sets, and will contribute their results to a shared, central comparative analysis effort.
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| Action Plan: Cell and tissue resources (well characterized samples) | Major focus should be on the biological tissues researchers are going to study because that's where most of the variation will be. It is to stress that the pathology and the quality control of the liver tissues are of fundamental importance. There is fantastic material available to study liver proteomics. Whether the existing material can cover the scope of this HLPP project is however not yet known.
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| Action Plan: Platform diversity and protein standards in bridging the proteomic technologies in HLPP (separation, identification, characterization) | The diverse nature of proteins leads to a requirement for platform diversity and for a full array of existing and emerging technologies included in the project. The choice of platform depends upon the project and the level of proteins of interest and effort to one prescribed technology or method of research should not be reduced. The major proteomic technology platforms that are currently used are 1) 2D PAGE-mass spectrometry (MS) with protein identification by peptide fingerprinting with MALDI-ToF MS or sequencing tagging and post-translational modification determination by LC-MS/MS; 2) multi-dimensional protein identification technology LC-MS/MS or ‘MuDPIT’, 3) stable isotope labeling of proteins such as isotope affinity tag technology or ‘ICAT’; and 4) protein retentate-MS such as surface-enhanced laser desorption ionization or ‘SELDI’. These are the primary technologies that would be used in HLPP.
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| Action Plan: Scope of U.S. participation to HLPP | The major recommendation is to focus on the biology. The field of proteomics is developing rapidly and therefore techniques are at the present time not the most important aspect. The technology is a tool to get us where we want to go as biologists. Defining the biology and the questions researchers want to ask are most important. Therefore the scientific objectives need to be defined first.
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| Action Plan: Recommendations for action plan | From the Field of Human Proteome to the Future of Human Biomedicine
The strongest and most compelling argument for a proteome initiative that focuses on the liver is the essential and multi-function role of the liver in human health and disease. Liver disease afflicts more than 10% of the world population. Liver pathogenesis remains however largely undefined and most liver diseases remain poorly diagnosed, staged and treated. In addition, many proteins in plasma are synthesized in the liver and change with disease in the liver, as well as systemic responses to inflammation and disease processes in other organs. Finally, protein signatures in preclinical study models and in human liver samples could be used as an effective way to understand pharmacology and toxicology. Understanding the liver proteome will accelerate the development of diagnostics and therapeutics towards the diseases of this organ and also facilitate drug discovery. A proposal for an action plan for the initial phase of an international liver proteomics initiative has been sketched out and funding to that effect has been committed by several governments and agencies ($10M from Chinese Government, $2.5M from Genome Canada, $2M from INSERM and ARC in France). Other participating countries include Japan, Korea, Germany, Australia and the United-Kingdom. The importance of liver proteomics is therefore reflected by the commitment of countries worldwide to support, in a major way, such an initiative.
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