Partners in pathway lucidation

Marketing agreement between Roche NimbleGen and Sigma-Aldrich seeks to ease epigenetic research bottlenecks

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MADISON, Wis.—In a deal ultimately aimed at advancing epigenetic research, Roche NimbleGen Inc. and Sigma-Aldrich announced last month that they will align their complementary technologies, Roche NimbleGen's ChIP-chip high-density microarrays and Sigma-Aldrich's GenomePlex.

By co-marketing each other's products, the companies hope to facilitate chromatin immunoprecipitation-on-microarray (ChIP-chip) research and provide researchers with a complete workflow solution. The companies also plan to publish protocols for ChIP-chip research and provide technical support to researchers integrating the two technologies.

"One of the requirements and bottlenecks in the ChIP-chip workflow is efficient amplification of targeted sections of DNA," says Kary Staples, manager of global marketing communications for Roche NimbleGen. "This is fulfilled by the GenomePLex WGA kit from Sigma. The other bottleneck is the high-resolution microarray detection, which is fulfilled by Roche NimbleGen's ChIP-chip microarray. Together, these two products complete the ChIP-chip workflow and provide a strong synergistic solution to the epigenetic research market."

Roche NimbleGen's ChIP-chip microarray is a 1 x 3-inch glass slide that contains up to 2.1 million DNA oligonucleotides which are used for parallel analysis of different samples. The ChIP-chip array combines chromatin immunoprecipitation with microarrays to understand the DNA-protein interactions. It is used to identify DNA binding sites for transcription factors, polymerases and histone modifications. The arrays are used in key epigenetic applications where transcriptional regulation and chromatin structure changes are key factors for biological processes, like differentiation of stem cells.

Sigma-Aldrich's GenomePlex Single Cell Whole Genome Amplification Kit supports whole-genome amplification from a single cell, resulting in a million-fold amplification yielding microgram quantities of genomic DNA. The kit can be used in numerous applications, and is suitable for use with a variety of cells, including fibroblast amniotic cells, renal cancer cells, plant, epithelial, leukemia and polycarbonate fixed cells. After purification, amplified DNA can be analyzed in a manner similar to any genomic or chromosomal DNA sample. A number of downstream applications may be performed, including QPCR, STR analysis, SNP analysis, Comparative Genomic Hybridization (CGH), microarrays and other genotyping analysis.

Together, the platforms will enable researchers to effectively study the entire genome for epigenetic interactions between DNA and DNA-binding proteins to determine regions of the genome that are transcriptionally active or repressed and the mechanisms that regulate these processes, says Adam Imiolek, genomics marketing lead at Sigma-Aldrich Research Biotech.

"Our technologies work really well together," Imiolek says. "Our technology works well with fragmented DNA such as one derives from a ChIP-chip experiment, and Roche NimbleGen has the analysis portion with a high-resolution array, and we want to present that as a unified solution to our customers."

Understanding the fundamental epigenomic and genomic regulatory pathways underlying normal cell growth and tissue differentiation, as well as changes in regulatory control associated with disease, is crucial for the development of drugs that target these pathways, Imiolek says.

"I see the field developing to where high-density arrays allow researchers to look for more rare interactions and allow for better comparisons between a control and a manipulated sample," he says. "I think these methods can be utilized in some of the broader epigenetic screening studies in which people are using archived samples for particular diseases to derive better results with smaller DNA samples."

Ultimately, Imiolek says he views the collaboration as "pathway lucidation."

"Epigenetics is a means of gene expression, and ultimately, disease states are due to changes in gene expression," he says. "In the case of epigenetics, you have factors beyond the DNA sequence, environmental factors that also lead to diseases. This is particularly apparent in cancer research, where researchers are focused on understanding epigenetic changes in cancer. In the end, looking at transcription factors, translation factors and changes in expression between normal and malignant cells are changes that one wants to understand and control in order to create a drug that may cure or inhibit cancer."

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