NimbleGen last week was awarded a $1.7 million, four-year grant from the National Cancer Institute to map regulatory pathways in cancer in collaboration with the Ludwig Institute for Cancer Research and Iceland Genomics.
Specifically, NimbleGen and the LICR's University of California, San Diego, branch will co-develop next-generation chromatin immunoprecipitation (ChIP)-on-chip methodologies to map transcription factor binding sites throughout the human genome. Iceland Genomics will provide samples from its clinical cancer database to be screened for TF binding using the new methodology.
While the immediate goal of the project is to aid in cancer research, particularly breast and prostate cancers, the NCI grant will ultimately enable NimbleGen to add next-generation ChIP-on-chip technologies to its product portfolio courtesy of the federal government.
According to Roland Green, NimbleGen's vice president of R&D and chief technology officer, the NCI-sponsored project will definitely result in a commercial product.
"Once we have the sites mapped, we plan to offer TF-specific arrays that cover all of these binding sites."
"We are planning on mapping TF-binding sites throughout the human genome in normal and tumor samples. Once we have the sites mapped, we plan to offer TF-specific arrays that cover all of these binding sites," Green told BioArray News in an e-mail this week.
He said that NimbleGen is "seeing a wide range of demand for" its ChIP-on-chip technology and that the company expects this market "to be one of the largest growth areas for microarrays."
Green said that demand "ranges from basic biology and the understanding of the functioning of a cell to searching for signatures for tumor types and disease states. Because it provides a direct look at the interaction of DNA and the proteins that regulate DNA, it offers researchers a new tool for unraveling the complexities of gene regulation."
The company expects the project to further reduce the cost of its ChIP-on-chip technology an initiative that it began in March when it introduced an array-reuse methodology to cut costs for customers (see BAN 2/23/2005).
That technology enables arrays to be hybridized with a sample, and then have the sample stripped away, leaving the oligos on the array intact. The array can then be rehybridized with another sample.
According to Green, the company now plans to reduce the cost of ChIP-on-chip experiments further "through the development of additional array-reuse protocols and three- and four-color hybridizations." According to a statement from NimbleGen, the company intends to use the new funding opportunity "to increase by threefold the number of samples that can be studied on a single microarray as well as reduce experimental costs."
In the NCI-funded project, LICR will perform the chromatin immunoprecipitation steps, and NimbleGen will be responsible for the array manufacture and hybridization. Both groups will work together on the data analysis, Green said.
Iceland Genomics, which shares office space with NimbleGen's Icelandic subsidiary in Reykjavik, will provide samples from its clinical cancer database to be screened for TF binding using the new methodology. Iceland Genomics helped NimbleGen set up shop in Reykjavik and licensed NimbleGen's array technology in 2002, but as of today, Green said the two have no official business partnership.
Bing Ren, who heads LICR's laboratory of gene regulation, said in a statement that he expects the project to enable a more "comprehensive analysis of the function of several transcription factors involved in breast and colon cancers."
Like Iceland Genomics, Ren's work with NimbleGen is not limited to this particular effort. His group at LICR also worked with NimbleGen to map promoters in cells as part of a greater project to understand cellular logic, which the partners published in Nature in June (see BAN 7/6/2005).
Ren told BioArray News in July that NimbleGen's high-density array technology gave it an advantage in the ChIP-on-chip market.
"They have an advanced technology that can synthesize high-density arrays that have close to 400,000 oligos on each array. So to represent the entire human genome, we can use roughly 38 of these arrays," Ren said at the time.
That kind of density has given NimbleGen a technological edge over rivals in the market for ChIP-on-chip applications, even though the Madison, Wisc.-based firm is dwarfed by Bay Area competitors like Affymetrix and Agilent. For example, with 900 employees, Affymetrix outnumbers NimbleGen in company size by 15 to 1. However, those rivals don't plan to let NimbleGen's technology pass them by.
Agilent Technologies, for example, launched its own ChIP-on-chip service in January. Last week, Scott Cole, Agilent's microarray manager, told BioArray News that his company sees growing demand for applications like array comparative genomic hybridization and ChIP-on-chip, and that it is planning to quadruple density on its custom arrays to 185,000 features per array from its current 44K offering by next year (see BAN 10/12/2005).
"The past several years have been really dominated by gene expression. But what we are seeing now is a transition from just a gene expression world with some SNP analysis to what we see as a multi-application microarray world," Cole said last week.
Agilent added ChIP-on-chip to its portfolio through its acquisition of Computational Biology, a spin-off from the Massachusetts Institute of Technology (see BAN 1/12/2005).
At the time, Fran DiNuzzo, vice president and general manager of Agilent's Integrated Biology Solutions business, said in a statement that the "acquisition is strategically important to the expansion of Agilent's microarray platform into new array-based genomics applications." DiNuzzo also estimated that applications for ChIP-on-chip technology in disease research, drug discovery, and drug development will comprise up to 10 percent, or at least $100 million, of the microarray market by 2007.
Affymetrix has also played in the market for studying how regulatory proteins control gene activity by launching its own line of tiling arrays (see BAN 10/27/2004). However, with Affy's attention to its new Mapping 500K Array Set and Human Exon Array products, it is unclear how much of a priority Affy's tiling arrays are for the firm at the moment. Affy did not return calls seeking comment by press time.
— Justin Petrone ([email protected])