Thursday, May 27, 2010

Genetic interactions in powers of ten

During my PhD at EMBL I attended a talk by Peer Bork where he said that computational biologists have the luxury of being able to work at any level of biological organization (atoms, cellular interactions, organism, ecosystems, etc) . At the time his lab was starting to work with metagenomics and his talks would cover the whole range of topics from protein domains to ecosystems. This idea of studying biology across this different scales reminded me of a very inspiring short movie entitled "Powers of Ten" (Wikipedia entry). This 1977 short movie was commissioned by IBM and it was written and directed by Ray Eames and Charles Eames. It takes the viewer on a journey in space from the very small atomic resolution to the outer reaches of the universe in incremental steps of powers of ten. Its only about 10 min long and if you haven't already seen here is below the embed version (while it lasts):

With all the different applications of genetic interaction screening going on here in the Krogan lab we though it would be interesting to write an essay that would, in the same spirit of this short movie, take the reader on a journey across different scales of biology. The essay was just made available online and I hope you enjoy the ride :).

We hope it serves as a tutorial for people interested in using genetic interaction data. There is more and more of this sort of data being deposited in databases and only a small fraction is being used to its fullest potential. We tried to show several examples of concrete findings that were first hinted by genetic interaction data.

Additionally we were trying to make the point that developments in high-throughout methods are decreasing the limitations of what can be observed in biological systems using the same methodologies. This is interesting because it challenge us to build models that can explain biological systems across different layers of biological organization. How does a change in DNA propagate across these layers ? Can it change the meaning of a codon, impact on a protein's stability/interactions, affect the action potentials in a neuronal cell and how species interact ? As we increase our capacity to monitor biological systems we should not only be able to tackle specific layers (i.e. understand protein folding) but we will eventually be concerned with coupling this different models to each other.