Recorded: 01 May 2000
Jeff: The concept of mating type switching has inherent in it several problems, and they’re all related. Solving those problems as a nest constitutes the contribution that I think we’ve collectively made. The concept of the cassette model means that there’s a silent place in the genome, an active place in the genome, and a mechanism for moving the DNA from one place to another. So those are the issues. Why is it silent? How is it activated? How does it move? It’s those issues. One of the things that I love about Amar was that there was this period in 1977 and for about another year, that the cassette model was genetically proven.
Amar: But no one would believe it.
Jeff: We had clear evidence of where the silent copy was, that the DNA was moved—genetic information was moved from it. It was perfectly clear to us but a lot of people couldn’t handle those genetic arguments. They needed a physical proof. They needed the DNA clone and a demonstration that it was a silent place in the chromosome and an active place in the chromosome and that you could see it move. So the initial focus then, was on getting that clone.
One of the mental pictures that I always have is that soon after we set up the yeast laboratory, and set about the mechanics of cloning the mating type locus, Jim, I think, took a little vial—one of these slants that are full of agar and there’s a black screw top cap on it. And he taped it to the refrigerator. This was the vial that we were going to put the mating type locus clone in and I remember that blue tape, I still remember this… That was the symbol of the mission of the first year or so.
Again, this was before—or just at the beginning of—transformation in yeast and at the beginning of a lot of the cloning techniques. That first year or so was assembling the tools it took to come up with a way in which we could identify the clone that had the mating type locus DNA on it. So that first period was a combination of assembling more genetic demonstrations.
But we simply kept hitting this wall, the people who couldn’t get it. And so, all right, if you get a clone and you give them a gel and it’s got three bands on it: The active locus and the two silent locuses, everybody got it. It’s in high school texts now. It was that transition from the genetic proof to a physical proof that was really the highlight in that first several years.
Amar Klar and Jeff Strathern worked together in the Cold Spring Harbor Yeast group from 1977 till 1984 where they made outstanding discoveries about the mechanism of mating type switching in yeast.
Amar Klar, is a leading yeast geneticist, concerned with the molecular biology of gene silencing and mating-type switching. Klar came from India to the University of Wisconsin in 1975 to receive his Ph.D. in bacteriology. From 1977 to 1984, he worked with Jeff Strathern and Jim Hicks in the Cold Spring Harbor Yeast Group studying the mechanism of mating type switching. Klar served as Director of the Delbruck laboratory from 1985 to 1988.
He left Cold Spring Harbor to join the ABL-Basic Research Program as Head of the Developmental Genetics Section. In 1999, Klar joined the National Cancer Institute Center for Cancer Research and is now a Principal Investigator in the Gene Regulation and Chromosome Biology Laboratory at NCI-CCR.
Jeffrey Strathern, a leading yeast geneticist, obtained his Ph.D. from the Molecular Biology Institute at the University of Oregon in 1977 and then moved to Cold Spring Harbor Laboratory, where he became a Senior Staff Member with the yeast genetics laboratory.
In 1984, he joined the ABL-Basic Research Program at the NCI-FCRDC. His research remains centered on aspects of gene regulation and genetic recombination as revealed by studies in yeast. In 1999, Strathern joined the Division of Basic Sciences, NCI. Strathern worked together with Amar Klar and Jim Hicks in the Cold Spring Harbor Yeast group from 1977 to 1984 where they made outstanding discoveries about the mechanism of mating type switching in yeast.