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The Bioengineer and the RNA Switch

  • Title: Research Fellow, Department of Genetics, Harvard Medical School
  • Education: PhD, Boston University, 2003
  • Recommended by: George Church

Farren Isaacs had been in hot pursuit of synthetic biology long before landing a postdoc position with George Church. Isaacs, who has a background in bioengineering, says he has always been interested in understanding problems in biology and medicine from a quantitative and interdisciplinary approach.

“As a graduate student, I was really interested in engineering gene regulatory networks and finding ways to quantitatively describe the behavior of a system at the molecular level,” says Isaacs. “I wanted to understand how networks of genes and proteins and RNA molecules all interact, so that was my first foray into engineering cells.”

During his graduate work, Isaacs was struck by the lack of available tools that allow researchers to turn on and off cell expressions as well as interface with various genes, proteins, and metabolites. “I really became inspired to work on developing the key enabling technologies to engineer cells,” he says. “So I actually developed novel sets of RNA switches that actually allow one to control the expressions of any target genes that you would want in prokaryotes.”

He was motivated by a desire to develop ways to probe and regulate genetic and biochemical components. From there, he says, the next logical step was to begin looking at the larger picture. He became interested in scaling these methods to the genomic level and set about trying to discover ways to employ these RNA switches all over the genome in order to control any genetic development that he desires. It is from this work that he became interested in the large-scale genome engineering that led him to George Church’s lab.

Currently, he is focused on researching foundational technologies in order to develop whole-genome engineering methods. This requires the ability to synthesize larges stretches of DNA, and then take the fabricated DNA and introduce it back into the genomes of cells. “The idea is to be able to manipulate whole genomes and change cellular properties as a method to make scientific discoveries, as well as applications directed towards new types of drugs and ways to engineer cells,” says Isaacs.

To meet some of the challenges in his research, he says it would really make a difference to have methods for making quick changes to basic genetic elements, be they promoters, genes, or non-coding RNAs. The next step would be to develop effective strategies to introduce these changes to the genome, which he says could involve computational design as well as combinatorial approaches coupled with directed evolution and selection.

Looking ahead

Over the next five years, the goal of Isaacs’ research is to devise a framework for researchers in the bioengineering field to direct cellular engineering and develop a way to evaluate how new types of technologies affect cell function. “I really think that it would be great to take these huge volumes of datasets that are coming out, apply some of the fundamental technologies that myself and others are working on, and really make an impact on the understanding of how cells function and use that knowledge to do useful things with cells,” he says.

Publications of note

In May of 2006, Isaacs and his colleagues published a paper entitled “RNA Synthetic Biology” in Nature Biotechnology. In it, they reviewed some of the key research that has come out over the last few years in the emerging field of synthetic RNA engineering, including Isaacs’ own work.

And the Nobel goes to …

Isaacs says he would like to be awarded the Nobel for developing new biotechnologies and cellular engineering that would have a significant impact on health, the environment, and society at large.

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