Charles Boone is a professor at the University of Toronto, Canada. His research focuses on developing an automated approach for genetic analysis in yeast. This work has enabled the mapping of genetic networks on a large-scale and the determination of the function of all genes in a yeast model system. The function of many yeast genes is conserved in humans and this work has the potential for discovery of therapeutic drug targets. He is the chair of the Molecular BioSystems editorial board.
When did you decide you wanted to be a scientist?
I really liked doing science, and when I went to university I tried to get summer jobs in science. But the reality is I just loved doing research. Basic science was the fun part – figuring out how life works. When I go to hang out with my hockey team, they all wish that they were professors. At one level or another, they all do cool things too but they realise that the world of science gives you a lot of freedom and nowadays there’s a worldly aspect to it. But I didn’t know that when I started, so the bottom line is that science was interesting and something I really liked.
You started as a chemist, how did that come about and how did you then move to biology?
When I went to university I decided to study things I’m not very good at to learn more, so I studied Maths and Chemistry. I’m not a mathematician but by the end of my math course I was in classes with the geniuses. They’d be reading a book in class and I’d be trying to figure out what fuzzy logic was. I really liked chemistry but I’m like those guys that were looking for the chemical basis of life. Once I’d seen what you can do with microbiology, I thought it was really exciting so even though we didn’t have much of that at our university at the time, once I read about it I had no problem switching over straight away.
I know several people who’ve done the move from chemistry to biology, I think the biology to chemistry switch is probably more difficult?
There’s probably some problems making the shift either way. I don’t have the best grounding in some bits of biology and in some of the breadth of biology I’d like. But I’d agree that generally biologists don’t shift to being mathematicians or chemists. Chemistry is a major foundation of almost all sciences so that may make it easier.
Your work is in yeast genomics, why did you choose to research this topic?
Yeast is a major model system. I went into it by chance, because going from chemistry to biology I had to find someone to take me into their lab as most of them were sceptical that this chemist could do biology. But I have to admit that when I started working on yeast I realised that it’s an almost perfect organism for a transition from chemistry to biology because you can do almost anything with yeast. And it’s so simple – it’s a single cell so you don’t have to worry about development, at least in a major way (there are developmental programs) and you don’t have to worry about different tissues.
Can you tell us more about what you do in your lab?
There is a fairly large community working in yeast molecular genetics and genomics – about a thousand labs around the world. And there’s an incredible database called the sacaromyes genome database that houses all the information. The idea is to understand how yeast works at the level of almost every nucleotide in the genome and one of the ways we do that is to delete each gene individually. This has defined 1000 of the 6000 genes to be essential in yeast – so if you delete an essential gene the yeast dies. This indicates that most genes in eukaryotic organisms are non essential and we think one of the reasons for this is that pathways in the cell are wired with many back up pathways for any individual essential process in the cell. So there are many ways to solve a particular problem that the cell may encounter and we try to decipher which pathways are working together to solve essential functions and come up with a wiring diagram for the cell.
To do this we have identified all possible double mutants of yeast – which comes to the order of 18 million. We’ve developed a system that we call synthetic genetic array analysis that allows you to take a gene and either delete it if it is non essential or make a partially functional version if it is essential. Then make all possible double mutants with that gene and score if the mutant dies or has a fitness phenotype than is worse than we’d expect by combining the two single mutations, so it’s quantitative.
We call that a genetic interaction – so we’re scoring genetic interactions and have come up with our genetic interaction map. We hope to link each gene to those of related function and sort all the genes in a cell into clusters that work together and thereby provide a global view of how the cell is wired functionally.
Million dollar question – why do we care about yeast genetics?
Because it is a fundamental eukaryotic cell and if we can understand how it works we’ll have a much better understanding of how human cells or higher order cells in a eukaryotic organism work and then the genetic network problem is important because it is a model for the genotype to phenotype problem where if you sequence an individual and you know their variations, which combinations of mutations or alleles of genes control pathways and lead to inherited phenotypes. And no-one knows how to solve that problem beyond just the single gene.
What would you be if you weren’t a scientist?
There are two things I think I would like to be. One is an explorer, but it’s such a drag that the world’s been figured out by all those great British explorers because that would have been fun. And being a hockey player would have been way up on the list but maybe not as realistic as being a scientist. But I think the science path I took is related to exploring because it’s a great avenue for coming up with dreams and going out and trying to find them.