At CHI’s Proteins to Profits in Munich, Europeans Compete to Put Proteins on Chips
Judging by the plethora of competing technologies showcased in Munich at last week’s “Proteins to Profits,” a two-part conference sponsored by Cambridge Healthtech Institute, it seems too early to judge who will become the Affymetrix of protein arrays, or even if one technology platform will outflank the others. A common complaint throughout the three days, both in the talks and in panel discussions, centered on the lack of appropriate capture reagents — antibodies or other binders — to analyze proteins with sufficient specificity and sensitivity. Other talks pointed out the need for assay automation, and for computing tools to cope with the growing tide of data. A summary of notable presentations follows:
Protein Arrays: Problems and Potential Solutions
Matthias Uhlén from the Royal Institute of Technology in Sweden caught the audience’s attention with his high-throughput proteomics experiments using polyclonal antibodies, a class of capture agents that have fallen into disfavor with many researchers because of their lack of uniformity and limited availability. But Uhlén showed he could generate polyclonals with little cross-reactivity against the majority of human proteins encoded by chromosome 21. He also demonstrated how he used the polyclonals on human tissue arrays to study protein expression and localization. Within a future European consortium, Uhlén said, his group is planning to raise antibodies to the majority of human proteins, although he acknowledged that “the bottleneck is the rabbits.”
Generating enough antibodies to use in an experiment is not the only problem. In addition, the chemical environment inside a cell often destroys the antibodies’ shape, causing them to fail. However, Dominik Escher from Zurich-based ESBATech presented a possible solution: his company’s yeast-based in vivo technology allows researchers to create modified single-chain antibodies that he claimed also function within cells.
Several other protein array companies presenting at the conference chose to work with cytokines, which can serve as markers for a variety of diseases, as a training set to test miniaturized ELISAs. Michael Egholm, of New Haven, Conn.-based Molecular Staging, presented results demonstrating how his company is developing cytokine arrays using its rolling circle amplification technology, which can increase the sensitivity of the assay. Molecular Staging has defined sets of cytokines involved in autism and cerebral palsy, a neuromuscular disorder caused by brain injury at birth, and plans to publish results soon. Both disorders are currently difficult to diagnose at the early stages of disease, and Egholm told the audience about his personal stake in the company’s reserach: his three-year-old son suffers from cerebral palsy.
More Than Just Arrays
Earlier this year, Cellzome and MDS Proteomics published two competing papers back-to-back in Nature on the large-scale analysis of protein complexes in yeast. At the conference, Anne-Claude Gavin from Cellzome and Matthias Mann of MDS gave back-to-back presentations during the first afternoon session. Besides a summary of Cellzome’s published work, Gavin presented human data showing that “[the] TAP [method] works in human cells” and noted that Cellzome has started working in the areas of inflammation, oncology, neurology, and metabolic disease.
Mann, who also leads a lab at the University of Southern Denmark, in Odense, focused on his academic work involving mass spectrometry analysis of proteins from cell nuclei and signaling protein complexes — including tyrosine phosphorylation.
Occasionally a speaker tried to remind the audience of the conference’s greater goal: facilitating drug discovery. “Early killing is good killing,” said Pierre Legrain of Paris-based Hybrigenics, referring to the early elimination of unsuccessful drug targets. And GeneProt’s Keith Rose felt motivated by the extended patent life of a drug that comes with a reduction in development time. “That’s how we get to more profits,” he said.