Recorded: 17 Jan 2003
The surprising things that came out of this project that I started off on were that we found some deletion mutants of SV40 which appeared to be lacking a protein which no one had ever discovered before as being made by SV40. So when I first arrived at the lab there was a certain faction that said, well why would anyone want to work on SV40 because we already know everything there is to know about this. And of course that absolutely turned out not to be the case. So where I found these mutants that had bits of the SV40 chromosome missing. We were really puzzled to know what the consequences of this would be, and so we went on to study the proteins that SV40 was making.
And actually [we] discovered a totally new protein. The common major protein of SV40 is called t-antigen and this is the protein that was already well known to be associated with the ability of SV40 to grow and to cause tumors and so on.
And it turned out that there was another protein made from the same gene called small t-antigen which was, for obvious reasons, a smaller version of large t-antigen. Firstly, it was completely unknown how it was that one gene could actually make two different proteins. And the second thing was of course nobody had any idea what the function of this protein was or, indeed, whether it had any function at all.
So what we’re really experiencing here is the discovery of RNA splicing and that actually happened in two different systems. It happened in adenovirus and it happened in SV40. So it was a very exciting period. The adenovirus group that I actually wasn’t involved with were spending a lot of time running around the corridors reporting rumors from other labs that something interesting had been found in adenovirus.
So the people that were involved that I can recall were Rich Gelinas and Tom Broker and Louise Chow principally. I’m sure there were others. I think Dan Klessig also is involved in that work. And so it turned out that several different groups had actually, at Cold Spring Harbor, had been separately working on adenovirus, different aspects of it and the stimulus of the fact that somebody outside the lab was about to report something exciting made them actually all sit down together and put all their data together and out of this, they actually realized through looking at the electron micrographs as well as some of the biological data that there were alternative messenger RNAs being made of certain genes of adenovirus. So they were then, of course, one of the first group to report RNA splicing in adenovirus.
Ashley [Dunn] was part of it, yeah—[he was] part of the adenovirus group also. I think he was working on something slightly different but—yeah, so it was a very competitive but also very exciting time for these two groups at MIT and at Cold Spring Harbor competing to be the first out.
And of course they both reported their results simultaneously in the literature and also at a Cold Spring Harbor meeting which was held.
Merilyn Sleigh is a pharmacologist, molecular biologist and dean in the Department of Life Sciences at the University of New South Wales. After completing her Ph.D. at the University of Sydney in pharmacology and another PhD in molecular biology at the Commonwealth Scientific and Industrial Research Organization (CSIRO), she came to Cold Spring Harbor Laboratory to work under Joe Sambrook as a postdoctoral fellow researching the protein production of SV40. She returned to CSIRO, establishing one of the first laboratories in Australia using genetic engineering approaches to study influenza virus structure, evolution and gene regulation. She has become involved in developing the biotechnological industry in Australia. Sleigh is founding director of the Australian Biotechnology Association and is currently Chief Executive of EvoGenix, a start-up biotechnology company located in Australia.