Armed with €1.8 million ($2.4 million) in seed funding, a European consortium hopes to catalog and eventually produce all binding molecules that can help detect and identify human proteins.
“The objective is to set the basis for an infrastructure of binding molecules against the human proteome for detection, validation, and functional studies of the human proteome,” according to Michael Taussig, head of technology research at the Babraham Institute in Cambridge, UK, the coordinating partner of the consortium, called ProteomeBinders.
Officially formed a year ago, ProteomeBinders is made up of 26 European and two US partners. Last week, organizers held a four-day workshop in Austria covering similar efforts underway, new protein-detecting technologies, and ProteomeBinder’s participation in a new biobank being set up by the European Commission containing molecules and tissues.
Understanding the human proteome, including how it controls biological functions and the role it has in human disease, is one of the most significant challenges of the post-genomic age, Taussig said. But in order to get to that stage, there needs to be more information about binding molecules that allow for the detection of proteins.
“Antibodies are universal reagents for protein studies and they have the ability to quantify and detect proteins in all circumstances,” Taussig said. “However, only a small fraction of the proteome is actually covered by existing reagents.”
He estimated that there are binding reagents for about only 5,000 of the more than 100,000 proteins specified by the human genome. “That still leaves a lot of proteins to be covered,” he said. “One doesn’t know whether that’s important or not, but we think rather like the genome project, one ought to have at least one binder or set of binders for every target in the proteome.”
To be sure, ProteomeBinders is not the first initiative aimed at identifying protein-binding molecules. The Human Protein Atlas, a ProteomeBinders partner, currently has more than 1,500 antibodies representing more than 1,300 proteins, and 1.2 million images showing the expression and localization of human proteins.
The National Cancer Institute’s Clinical Proteomic Technologies Initiative for Cancer also is creating a reagents resource to serve as a central warehouse for reagents related to cancer research.
But according to Taussig, ProteomeBinders, while complementing the work of those and others’ efforts, also aims to be much more comprehensive by becoming a one-stop shop for all protein-binding molecules.
“We want to have everything in the resource,” he said. Some of that would be accomplished by linking to the work of other sources such as the NCI and the Human Protein Atlas.
“The key element is that there should be access to these things; they shouldn’t be locked up in a company,” Taussig said. “They should be accessible to the whole community at cost. Not free but at cost.”
In addition to cataloguing all the binding molecules, ProteomeBinders will eventually be producing them, possibly by 2010.
“This will set up as an open-access resource in due course over a number of years, generating the binders and making them available from some centralized place, or from a network of places,” Taussig said. By doing so, he said, standards in the production of reagents will finally be established.
“We’re quite concerned about the lack of quality control that seems to exist in the commercial sector,” Taussig said. “People often complain about the poor quality of reagents which they buy. So we would like to put in place a sort of gold standard quality control system by which all binding molecules could be referenced or benchmarked.”
The partners that make up the consortium at the moment include those working in the areas of antibodies, alternative binding molecules, small chemicals, high-throughput assays, and bioinformatics.
“We’re quite concerned about the lack of quality control that seems to exist in the commercial sector. … So we would like to put in place a sort of gold standard quality control system by which all binding molecules could be referenced or benchmarked.”
Andrew Bradbury, a project leader at Los Alamos National Laboratory and a ProteomeBinders partner, said the consortium could serve to fill knowledge gaps in the field.
“This is a field that’s far more advanced in Europe than it is in the US on the whole, with the exception of a few labs,” Bradbury said. “The reason I’m keen to participate is to find out what’s going on in Europe and to keep myself up to date with that concept of a project.”
There are no commercial partners in the consortium, however. Taussig said that as efforts now focus on getting ProteomeBinders started and clarifying goals and methods, the organizers are concerned that the industry would not be committed enough to the effort since there is no financial payout yet at this stage.
However, attendees at last week’s meetings included Applied Biosystems, Roche Diagnostics, and Invitrogen, signaling their interest in ProteomeBinders’ activities, Taussig said. They can also join as associate partners, he said, and when and if the consortium gets to the point where it is producing the binders, it may look at contracting it out to commercial vendors.
The €1.8 million provided by the European Commission’s Sixth Framework Program over four years, is the only funding that ProteomeBinders has received to date, and is meant as seed money. For its next phase — during which the consortium will be evaluating binding types, and creating quality control designs and production designs — it is currently drafting a proposal for an additional €3 million in funding spread over three years from the EC’s Seventh Framework Program.
It all builds up to eventual production of the binding molecules.
“What we’ll be doing for the next three years will be setting in place all the necessary methods and identifying all the right locations for high-throughput binder production and high-throughput applications and bioinformatics,” Taussig said.