By Walt Jaschek
[This is the first in a series of articles on modern breakthroughs in science, commissioned by Sigma-Aldrich and its agency, BigWideSky, as content for “Tesseract,” a planned enewsletter intended for its clients in academia and scientific research. I tried to speak in the language of the audience, but to employ a style human and warm.]
“Would you people pleeeeeeeease quit talking about work?”
You can almost hear teenage Emily Nicolet of Davis, California, beseeching her parents across the dinner table.
Her mother, Peggy Farnham, PhD, Associate Director of Genomics at the University of California-Davis, says it’s not an uncommon plea. Dr. Farnham and her husband, Charles M. Nicolet, PhD, are also colleagues: Dr. Nicolet is Manger of the DNA Technologies and Gene Expression Core Facilities at UC-D, and both of Emily’s parents are distinguished for their groundbreaking work at the institution’s Genome Center. Conversations between them can quickly turn molecular.
At one such dinner in 2006, Dr. Farnham was the one complaining. She remembers criticizing the quality of data her lab was getting from the then-existing techniques of amplifying DNA from chromatin immunoprecipitation (ChIP) samples for hybridization to a genomic tiling array (ChIP-chip assays.) One technique – linker-mediated PCR (LMPCR) – was providing too great a signal-to-noise ratio. Another, pooling 50 replicated ChIP samples, was not feasible for multiple genome-wide analyses.
Between bites, her husband offered a suggestion. “Have you considered trying one of the WGA amplification methods they’re using in the lab performing Comparative Genomic Hybridizations? Somebody over there just gave me a pamphlet.” Dr. Nicolet handed it over.
Dr. Farnham saw the potential immediately. “Nobody’s tried this on ChIP-chip assays,” she recalls saying. “Let’s do it!”
It was probably about that time daughter Emily lobbed her mid-meal protest.
But the dinner dialogue proved an important catalyst.
Today the Farnham Laboratory at UC-D, a leader in genome-wide characterization of transcription factor binding sites and chromatin modifications, has abandoned the LMPCR and pooling methods and has completely switched over to the WGA technique for its research, getting what Dr. Farnham calls “really quite amazing” data from increasingly smaller cell samples.
“This level of amplification is critical to having enough material to put on the arrays,” Dr. Farnham says. “Using WGA, we just did a whole genome tiling of 38 arrays, going through every base in the genome, looking for a particular factor, and the data is really beautiful. We’ve done 200 arrays in the last six months and it works just as well for any of the factors we’ve tried.”
Miniaturization – getting more from less – is the trajectory of DNA research, Dr. Farnham says. The possible applications are many, but are particularly relevant to the future of medical science, where the ability to extract more sophisticated information on defects and disease from even the smallest biopsy could lead to more evolved diagnosis and cures.
It was in 2004 that Drs. Farnham and Nicolet and their daughter Emily moved to Davis from Madison, Wisconsin, where Dr. Farnham was professor of oncology at the University of Wisconsin. “We all had great friends and colleagues there, but this was a chance to do something new and different at the Genome Center. It’s exciting to be part of a group thinking on this scale. Everybody has these great, genome-wide assays to talk about. The energy is high and the opportunity for collaborations is fantastic.”
In fact, Dr. Farnham’s most recent scientific paper, the latest of many published findings released this year by the Farnham Laboratory, has a collaborative twist. One of the co-authors of Comparison of Sample Preparation Methods for ChIP-chip Assays is also her frequent dinner companion and husband, Dr. Nicolet. “This is our first paper together,” Dr. Farnham says of the work, which compares three ChIP sample preparation methods differing in background noise and reproducibility of binding site identification.
And to think: this influential Farnham/Nicolet collaboration crystallized with that seemingly innocuous “Have-you-considered?” conversation in their dining room months prior. The incident supports this simple, three-part conclusion:
Some scientific advances occur over years.
Some, over decades.
And some, over dinner.
Walt Jaschek is now hungry.