 |
PAGE 1 OF 2
Professionals and amateurs compete on an equal footing to provide often surprising solutions. HHMI investigator David Baker sees it on a daily basis with Rosetta@home, a distributed network dedicated to solving big questions in protein folding.
This phenomenon of crowdsourcing—a term that journalist Jeff Howe lays claim to coining—has some interesting parallels with old-fashioned bucket biochemistry (my kind of science). Each requires a vast input and powerful filters to yield a pure nugget of information. In biochemistry—which often requires real buckets of biological material, such as liters of HeLa cells—the nugget is a few nanograms of scarce proteins that researchers need to begin the real work of understanding the machinery of life.
Fishing is one of my passions, but some of my most successful fishing expeditions have been scientific. Starting during my years as a postdoc with Jim Watson at the Cold Spring Harbor Laboratory and subsequently at the University of California, Berkeley, my colleagues and I went fishing for a very specific molecular target: transcription factors—key regulatory proteins that control the flow of biological information in cells. We used short segments of DNA as bait, hunting for a match among the tens of thousands of proteins in cells. We started with viruses and then found the first transcription factor in human cells, something we called specificity protein 1, or Sp1.
We've learned that transcription factors work by interacting with short regions of DNA once denigrated as “junk” that in fact control the activity of all our genes. You can think of transcription factors as specialized proteins that recognize DNA sequence “punctuation marks”—start and stop signals recognized by the enzymes that read and transcribe genes. The transcribed “messenger” RNAs go on to generate important products like hemoglobin, the iron-rich protein that carries oxygen in red blood cells. Not surprisingly, when gene regulation goes wrong, disease occurs: diabetes, cancer, inflammation, and heart disease among them.
Like collaborations in cyberspace that rely on many anonymous contributors, bucket biochemistry has inherent limits. For example, by measuring transcriptional events in extracts derived from mixtures of cell types, we can detect only average events, not the reactions taking place in individual cells or at a single gene locus. In short, biochemists like me have been missing the rapid, dynamic, and mysterious real-time events taking place in individual cells at specific genes. But now developments in fluorescence microscopy make it possible to witness transcription as it unfolds in real time, molecule by molecule, and in some cases even in living cells.
Photo: Barbara Ries
|
|
|
