Su Guo
In a press conference at Stanford on Monday, and reported later in the
San Francisco Chronicle, one of the scientists who received the Nobel Prize for discovering how RNA can turn genes off credited early experiments by UCSF's Su Guo, PhD, for sparking the research. Nobel Laureate Andrew Fire, a professor of pathology and genetics at Stanford's School of Medicine, highlighted experiments Guo launched when she was a Cornell graduate student. Guo is now assistant professor of biopharmaceutical sciences at UCSF.
We asked Guo about the early research:
Q. Andrew Fire says that your experiment as a graduate student ultimately led to the discovery of RNAi. What was that experiment?
A. As a grad student with Ken Kemphues, I was working on identifying the gene called par-1 that is disrupted in a C. elegans worm mutant. In worms with the mutated par-1 gene, the embryonic cells fail to undergo normal, non-symmetrical division. To determine whether I found the right gene or not, I tried a crazy experiment, which was to inject the "antisense" RNA of par-1 into the normal, wildtype worm. Antisense RNA is a piece of RNA that complements the organism's own RNA transcript. The craziness is the injection of RNA, since most people thought RNA would be easily degraded in an animal, and have no effect.
I found that the antisense RNA led to a gene-specific silencing. At the time, we thought that it was due to the antisense effect. Then I did my control experiment, which was to inject the "sense" RNA - that is RNA containing the same sequence as the organism's own RNA transcript. I observed that the sense RNA also led to gene-specific silencing. Andy Fire later found that double-stranded RNA is present in both of these RNA preparations, which accounts for the potent gene-silencing effect.
Q. How surprising was your finding?
A. I was not surprised by the antisense RNA effect, since we thought it was due to the antisense inhibition mechanism. However, I was totally surprised by the observation that my sense RNA worked equally well. If it were due to inhibition mediated by antisense, you would expect that the sense RNA should have no effect.
Q. How did you follow up on that finding?
A. We reported our finding in Cell in 1995. Later I used the same method to knock out another gene, reported in Nature in 1996. This made me realize that it was a quite general phenomenon, not just specific to the first gene I had been studying. The potent sense RNA effect was a big mystery to me. As a grad student, I did not know about double-stranded RNA, and how it would have got into my sense RNA preparation -- until Andy Fire made the leap and reported the key findings in Nature in 1998.
Q. How has your research focus changed since those experiments?
A. I moved on to do a postdoc at Genentech. Related to my interest in asymmetric cell division -- which the par-1 gene regulates, and which is a division pattern that stem cells use for self-renewal and production of differentiated cell type -- I studied how pluripotent cells commit and differentiate into dopamine-producing neurons, which degenerate in Parkinson's disease.
Q. What is your lab's aim?
A. We are interested in two major questions: How do pluripotent embryonic stem cells behave in vivo? And how do genes and the brain control an organism's behavior? We use zebrafish as our model organism in our study.
Related Links:
The Nobel Prizes: Medicine: Stanford Professor Shares Award: Landmark Discovery Showed How RNA Shuts Down Genes
San Francisco Chronicle, October 3, 2006
Su Guo, PhD
Su Guo: Guo Fish
UCSF Magazine, May 2003
