AARHUS, Denmark - While the mapping of the human genome provided scientists with a blueprint for understanding disease, Swedish researchers are trying to take the knowledge one step further, with the human proteome.
Mathias Uhlen, a professor at the Royal Institute of Technology in Stockholm, Sweden, is leading a 75-person research team on the project, which is funded mostly through a $30 million grant from the Knut and Alice Wallenberg Foundation.
"I think the Human Genome Project was fantastic," Uhlen told BioWorld International, "not for the DNA sequence, but because it defines the proteins. The problem then is, we don't know what the proteins are."
Uhlen spent a long weekend at the University of Aarhus, where about 60 researchers gathered Friday through Monday to talk about proteomics. It became evident during the "Workshop on Applied Functional Genomics" that Sweden is not the only country turning to proteins to understand disease. China is working with proteins to find the cause of hepatocellular carcinoma, a form of liver cancer in which half of the people inflicted worldwide are Chinese. Researchers in the UK, Germany and Denmark also are studying protein array technology. Researchers at the University of Southern Denmark in Odense have initiated modification-specific proteomics, an approach dubbed "modificomics" by Peter Roepstorff of the university's department of biochemistry and molecular biology.
Modificomics enables the detection of various types of protein modifications in proteomics. While Americans tend to use mass spectrometry to define expression proteomes, Europeans prefer gel-based proteomics, Roepstorff said at the conference on Sunday.
But Uhlen has a totally different approach. With genome-based proteomics, he focuses on one chromosome at a time. In his project, he wants to express 20 new antibodies a day, with the hopes of mapping 80 percent of the proteome in five years. The current funding allows his team to express five per day, which includes the screening of 700 tissues with every antibody.
"My vision is in 10 years we should have specific antibodies to all human proteins," Uhlen said.
His team already completed its work on chromosome 21 through a pilot project. It now is focusing on chromosomes 14, 22, X and Y.
A human body has more than 50 million antibodies, and there are tens of thousands of variations to proteins. Uhlen has pared down his project to focus only on the 24,000 non-redundant proteins.
Funding from the Wallenberg foundation will take the project through about four years of research.
That is when belonging to a European consortium could become a benefit. While at lunch on Sunday, Uhlen and Mike Taussig, the head of The Babraham Institute's technology research group in Cambridge, UK, discussed the prospects of forming such a consortium to share knowledge and resources throughout Europe.
"If we all know what is going on, we won't duplicate each other's attempts," Taussig said.
In order to attract companies to participate, Uhlen, who himself has founded five Sweden-based companies, suggested allowing the commercial entities to retain value with their reagents.
Like the human genome, the human proteome would become public property on a global basis, Uhlen said. But even those who mapped the human genome retained some value for themselves. The sequence is available, but not the clones that produced it. Uhlen would welcome the sharing of human proteome knowledge, but intends to use the antibodies to generate value in some way through various research collaborations.
Uhlen worries that strict rules requiring consortium members to share all information might deter commercial operations from participating. And the world needs their research, he said.
A consortium could allow members to retain rights to its methods, if they're willing to fund the research on their own. The consortium, on the other hand, would help fund research that will be shared among its members.
"There has to be some framework between complete freedom and complete privacy of your reagents" in forming a European consortium, Taussig said.
Uhlen is having similar talks of sharing knowledge among researchers through HUPO, the Human Proteome Organization. Aside from Uhlen, others are conducting proteome work, including the Sanger Center in Cambridge, UK, a couple of small U.S.-based companies, and research groups in Germany and China. Uhlen's research team is small, with only 75 people, while Sanger had about 500 working on the human genome. But Uhlen believes he can conduct an extremely efficient project with scale-up technologies.
He admits there are some critics who say he's encompassing too much. Others say his project is not comprehensive enough. But the intent of the project is to create a framework from which researchers can continue to work, and drug companies can better create effective therapies.
For instance, the first draft of the Human Genome Project had a lot of holes until international researchers filled the gaps. However, those gaps could not have been filled if Celera Genomics Group's J. Craig Venter hadn't done the work in the first place.
Uhlen hopes his work, as well, will have a far-reaching impact on disease.
"I can't imagine any researcher not using this kind of data," he said.