Mike Snyder: “It’s naïve to just look at one thing, we have to look at many levels”

Michael Snyder is the director of the Yale Center for Genomics and Proteomics, as well as Professor at Yale University. He studies protein function and regulatory networks using global approaches and high-throughput technologies, such as genomics and proteomics. During his visit to the PRBB he told us about the latest insights into human variation.

What are the pros and cons of high-throughput technologies?
There’s no question they are helping us advance in our knowledge. With genomics or proteomics experiments we discover things we would not have discovered by studying individual genes, and we have learned some basic principles out of these large datasets. Of course, there’s also an information overload and a lot of the data are still uninterpretable, but that makes it fun!

When will I be able to have my genome sequenced? 
Nowadays you can already get it done, if you have enough money, and I am sure all of us will have the opportunity to have our own genomes sequenced at some point at a reasonable price.

And would that be useful? 
Not that much right now, but the more genomes we have, the more useful they will be, because we can compare them and learn much more. Of course there are also ethical issues about the possibility of discrimination in employment and health insurance because of your genetic influences, and that is something that we will have to deal with first.

What have been the big surprises of biology in the last 15 years, after the human genome and Encode projects? 
The extent of divergence in gene regulation has been a big surprise – there’s a plethora of transcription factor binding sites (TFBS) in the genome, many more than expected. And they change so quickly between species.

How can we be so different from chimps, if we are 98.5% identical at the genetic level? 
I would say the difference between species is probably at the gene regulation level, rather than at the gene level. We have pretty much the same genes, but they are regulated differently and expressed at different times. They also interact with different proteins.

How about the differences between males and females – at the molecular level? 
One curios thing we have found is a difference in the expression of genes involved in osmotic stress. This could explain the physiological differences between men and women with respect to heart attacks and other cardiovascular diseases, which tend to be more frequent in men.

You work on pretty much anything: from yeast to human, on genes, RNA and proteins, from a single protein to whole cellular networks… what do you find most fascinating? 
I like them all, this is the nature of biology! We know almost nothing now compared with what we are going to learn in 20 years. There is so much to learn, and we follow whatever makes more sense to solve a problem. Yeast, for example, is very good to work out new technologies before using them in other models, or to solve basic problems. It’s naïve to just look at one thing. We have to look at nature at many levels.

This is an interview published in Ellipse, the monthly magazine of the PRBB.


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