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BY OUR PHARMA CORRESPONDENT
4 August, 2005: Pharmaceutical firms foresee potential opportunities as researchers around the world are planning to unveil a first draft of "interactome" – a complete set of cellular protein-protein interactions, by the end of the year.
The human interactome is considered the next big challenge after the human genome project. Scientists argue that a complete map of protein-protein interactions could provide a picture of what is actually happening in a cell, expose patterns they otherwise wouldn't see, and generate hypotheses that can be tested in more focused experiments.
Pharmaceutical companies believe that the new findings could throw open an altogether new facet of drug development. Because proteins tend to act in complexes rather than singularly, interactome maps can yield important functional clues for novel proteins, and reveal surprising details about known proteins.
There has been an almost exponential growth in pharmaceutical interest in protein complexes in recent years, focusing on what happens at the process (pathway) level.
The German firm Cellzome is collaborating with Novartis to research different pathway interactomes. And CuraGen, a New Haven, Ct.-based company is supposedly working on disease related interactome. Cellzome and Hybrigenics have published pathway-level interactomes, for tumour necrosis factor-alpha and tumor growth factor-beta signaling, respectively.
However, several researchers hold the view that due to the complex nature of the human cell, any interactome will be riddled with errors, and practically pointless, since most scientists don't have the tools to make use of the entire network anyway.
They also doubt the utility of a genome-wide human interactome. The human body contains an ever-changing protein kaleidoscope that varies over time and from cell to cell. Humans have some 25,000 to 30,000 protein-coding genes, many of which can be alternatively spliced. Each tissue and cell type expresses its own unique constellation of those genes. There may therefore be an entirely separate interactome for each cell type at each moment in time, making it practically impossible to catalog all of those interactions.
According to estimates humans are home to more than 200,000 protein-protein interactions, not counting the new proteins, and new interactions, created from alternate splicing and post-translational modification.
Still, journals have already published protein maps for the budding yeast, fruit fly, and nematode worm generated with high-throughput tools, and many say a human version is the next logical step. The number of interactions added to the Human Protein Reference Database (HPRD) – which has already catalogued nearly 30,000 protein-protein interactions published in peer-reviewed papers – has "really accelerated" in the last year and a half, say experts
As scientists continue to debate how best to approach the human interactome, drug developers are banking on some researchers who are already thinking about the next step: how best to use the information it provides. They predict the interactome will inspire a wave of activity to design well-crafted models that help researchers predict how protein pathways behave. If a model can forecast how a system will react to three times more of a particular signaling molecule, for example, scientists will know whether it's wise to tinker with that particular region of the human interactome, before they even try.
BY OUR PHARMA CORRESPONDENT
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