This story originally ran on Dec. 23.
By Tony Fong
The government of Germany has committed at least €37 million [$53 million] to create what is expected to be Europe's largest center devoted to developing new protein biomarkers for cancer and Alzheimer's and Parkinson's diseases.
Earlier this month, the German state of North Rhine-Westphalia provided the funding to create a new research facility at Ruhr University Bochum where scientists will attempt to discover, verify, and validate new biomarkers, and develop test kits based on them.
Construction of the 65,000-square-foot facility is slated to begin next year and to be completed in 2013. When finished, it will house about 150 researchers and administrative staff, according to Helmut Meyer, one of four researchers who will lead the center, currently called the European Protein Research Institute PURE (Protein Research Unit Ruhr within Europe).
Negotiations are under way with the German research organization Fraunhofer Society to rename it the Fraunhofer Institute for Protein Analytics and Biomarker Development, said Meyer, who is also director of the Medical Proteome Center at Ruhr University Bochum.
Planning for the center and negotiations for its funding began about two and a half years ago, said Meyer, who estimated that when all is said and done, funding could reach about €100 million [$143 million] during the next five years.
The money will come from the North Rhine-Westphalia Ministry for Innovation, Science, Research & Technology, the German federal government, and the German Social Accident Insurance, an umbrella organization of insurance institutions that provides coverage for occupational accidents and diseases.
The center will use the funding to hire new personnel and purchase new equipment, including an Orbitrap mass spec from Thermo Fisher Scientific; a MALDI mass spec; a system for laser microdissection; and a platform for infrared spectroscopy or Raman spectroscopy.
Initially, the center will direct research at the discovery of novel biomarkers for cancer — specifically bladder, liver, and lung — and for Alzheimer's and Parkinson's diseases.
The three cancers were chosen because they are of special interest to the German government, which is exploring whether certain jobs may contribute to workers developing those diseases, Meyer said.
"We have many people who have a higher risk to get such a disease … and those people are regularly tested yearly or every other year [to see] if they have any increased risk of getting sick," he said. The goal of the PURE research would be to discover and develop better methods of diagnosing individuals with disease at an early stage "before it's too late" for to medical intervention.
In addition to Meyer, another center head is Thomas Brüning, director of the Research Institute of Occupational Medicine German Social Accident Insurance at Ruhr University Bochum. Klaus Gerwert, chair of the biophysics department at Ruhr University of Bochum; and Jens Wiltfang, a professor in psychiatry and psychotherapy at the University Hospital in Essen, are the other two heads.
In the area of Alzheimer's and Parkinson's diseases, PURE researchers are following "new routes and new hypotheses" that explore autoimmune-related antibodies, "which may show up very early in the course of such a disease," up to 20 years before clinical symptoms appear, Meyer said.
By the time symptoms appear, the diseases are at a stage when treatments for slowing down their progression are extremely difficult, if not impossible, he said, and the hope is to catch them at a point when therapeutics may have efficacy.
While he and his colleagues wait for the center to be built, additional space at Ruhr University Bochum has been allotted for research related to PURE, and work is already being carried out there and at the University Duisburg-Essen.
High Performance, Not High Throughput
At least in the beginning stages, some of the research builds on Meyer's work. Meyer is co-chair of the Human Brain Proteome Project of the Human Proteome Organization and has done extensive research on a broad range of diseases and proteomics-related subjects. As a result, he said, he has firsthand knowledge about what doesn't work and what could be done to achieve greater success in proteomics research.
Indeed, rather than dong high-throughput proteomics, the center will use a strategy called "high-performance proteomics." In a 2007 article in Proteomics describing the approach, Meyer and his co-authors said that the problem with a high-throughput approach is that it leads to a long list of "qualitatively identified proteins" that may not actually be indicative of disease states.
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It's a concern that has been echoed by many in the proteomics community, which has now turned its attention to more targeted analysis, in addition to shotgun proteomics, as a strategy to determine which of the thousands of potential biomarkers that have been detected may have clinical use.
In the Proteomics study, Meyer and his colleagues wrote that in order "to find new biomarker protein candidates that may be useful for further studies, or for the development of diagnostic tests or even therapeutic targets, such proteomic studies have to be planned very critically from the beginning to get statistically significant results."
High-performance proteomics, in contrast to high-throughput proteomics, is a strategy in which "the data …is statistically validated, so we are doing biological replicates from human individual samples," Meyer said. "And we have worked out the scheme [that] allows us to start with human tissue samples and to harvest 1,000 cells and to do quantitative proteomics on the basis of only 1,000 cells in collaboration with pathologists and with doctors."
His lab, he added, is applying this strategy to develop biomarkers for about seven clinical indications.
While large-scale biomarker development initiatives have become routine, Meyer said that the inclusion of a pathology group — being led by Bence Sipos at the University of Tübingen — in the PURE center is a unique aspect that differentiates it from other similar efforts.
Just since the summer, other protein biomarker-related projects that have been launched include an initiative funded by the German Federal Ministry of Research, to develop biomarker-based tests to support protein kinase target studies [See PM 09/17/09]; a project started in Australia to find biomarkers that may be predictive of early onset of obesity-associated diabetes [See PM 08/13/09]; and the creation of a proteomics center by the Translational Genomics Research Institute that will initially focus on the discovery and validation of biomarkers for lung cancer in its broader goal of incorporating proteomics into personalized medicine [See PM 06/18/09]
According to Meyer, ignorance of disease development and progression has been a significant bottleneck in biomarker discovery, and "if you [don't have an] expert pathologist, you'd better stop the whole exercise," he said. "If we are going to analyze tissue samples from patients, we have to be sure that that patient is suffering from that disease that we are looking for, and the part of the tissue we are analyzing is … the disease part of the tissue."
In cancer, for example, there are multiple stages of disease, and one role of the pathologist is to define the stage of the cells being investigated. "And we need the pathologist in the further validation step if we are going for immunohistochemistry on thin sections first, and then the immunohistology with tissue arrays," Meyer said.
In addition to self-generated projects, PURE also plans to collaborate with pharma and diagnostic firms, for which the center would provide miRNA testing and epigenetics analysis, in addition to doing proteomics work, Meyer said. The PURE center managers have already been negotiating with firms such as Bayer HealthCare, Roche, and Abbott about possible collaborations. The center, he added, has received letters of intent from a few pharma and diagnostic firms for biomarker-based collaborations.
"At the moment we are an academic center, but that may change in the next year," Meyer said, adding that once the center becomes part of the Fraunhofer network of institutes, the research will move away from basic research to applied research. That will be manifested in the development of diagnostic test kits and biomarkers with therapeutic use, he added.