New gene-editing system enables large-scale studies of gene function.
In an effort to understand the enormous complexities of genes and proteins in a living organism, Drew Endy, assistant professor of biological engineering, is taking apart the pieces and putting them back together.
Endy and other researchers in the new field of systems biology are finding the experience a little like taking apart an engine and discovering they have no idea what most of the parts do.
Endy spoke on "languages and grammars" for programming DNA on Friday, March 3, as part of the spring 2006 seminar series on computational and systems biology sponsored by the MIT Computational Systems Biology Initiative (CSBi).
To simulate gene expression and get a sense of the dynamics of gene products, Endy and colleagues are coding the results of past experiments in a computation framework. "The goal is to engineer a surrogate genome that encodes a viable organism whose behavior is easier to predict," he said.
Applying engineering techniques to biology, he said, is a complementary approach to other ways of studying biological systems. If you take a gene and move it, what is the effect? It could result in too many variations to imagine.
"The approach we decided to take is to make a model of the system being explored using a computer so we can more quickly characterize the landscape of this system as it changes in the natural world," he said. The computer model allows more flexibility than a real-life laboratory experiment and allows the researchers to begin to develop a framework in which they can predict the effects of perturbations to the genome.
"Could we make a number of simultaneous changes to a genome that we could debug?" Endy said. To try, they assemble fragments of DNA to see if they can mimic Mother Nature.
To make the job easier, Endy and others at MIT are standardizing biological building blocks. In the 1800s, he pointed out, screw threads made in different machine shops were all slightly different, and a screw from one shop was not interchangeable with a screw from another. The industry agreed on standards, allowing many fields to move forward in a way not previously possible.
To that end, MIT has created the Registry of Standard Biological Parts so people can begin to use pieces of DNA in combination and see if they work. "You can grab a sequence and put it into your DNA synthesizer and give it a try," Endy said. "In Building 32, we have the DNA for a dozen terminators" (the DNA code that stops a genetic process so another one can begin). Anyone can try to fit the pieces together and engineer a unique living system, as students from around the world do each summer as part of the International Genetically Engineered Machine (iGEM) competition hosted by MIT.
Endy will speak Tuesday, March 21 at 6 p.m. at the MIT Museum on his research in synthetic biology and the social and political ramifications of the work.
CSBi is a campus-wide education and research program that links biologists, computer scientists and engineers in a multidisciplinary approach to the systematic analysis of complex biological phenomena.