October 2012

Biologically inspired innovation

Photo of the laboratory at Harvard University’s Wyss Institute 
The Wyss Institute aims to foster a friendly, collaborative research environment for scientists and clinicians.

A synthetic way of life
Silver’s lab — along with colleagues James Collins and Church — focuses on the manipulation of both prokaryotic and eukaryotic genomes and on developing new ways to do so. These synthetic biologists seek to engineer and build novel, man-made alternatives to our genes and pathways to construct living organisms or cells with well-defined outputs and, hence, new or improved functions.

The Church lab has been at the forefront of developing easier and cheaper genomic technologies. “We’ve helped lower the cost of sequencing about a million-fold and of engineering genomes using DNA from chips by similar amounts,” Church says. His lab, by helping to make genomics cheaper, faster and more accessible, has advanced fields ranging from ecology to medicine via chemistry and science policy.

There is no handbook for synthetic biologists to follow; they have had to develop their own sets of principles and rules, and those at the Wyss are at the leading edge of that work. As Silver explains, “Biology is not like electrical engineering in that it works in three dimensions — no wires — and over time scales that can be long. We seek new computational strategies and to move beyond trial and error in building complex biological systems.”

Meanwhile, Silver and Church recently co-headed Harvard’s International Genetically Engineered Machine — or iGEM — team, a group of biology students in an annual international synthetic biology competition aimed at the creation of devices to solve a particular issue. The team’s project focused on the development of a system to engineer synthetic gene circuits in plants rapidly and easily.

The team altered existing plasmid vectors to accommodate DNA modules from the Biobricks parts registry, a standardized catalogue of genes, vectors and regulatory elements. As a proof of principle, they inserted a gene encoding the protein miraculin (a peptide that makes sour tastes become sweet) into Arabidopsis to alter the taste of a bitter plant significantly without altering sugar content.

Christina Agapakis, a postdoctoral researcher at the University of California, Los Angeles, and one of the researchers supervising the iGEM team, explains that the team wasn’t allowed actually to taste their plants, so officially nobody knows for sure what it tasted like. However, she emphasizes, “We hope that these tools inspire and enable other iGEM teams to work with plants so that the toolkit can grow further.”

Bringing it all together
As Ingber looks to the future of his group’s organs-on-chip model, he says, “Finally, we can start by building the simplest model that re-creates physiological functions of interest and then add back cells one by one to explore their relevance for any response of interest.” But beyond cell biology, synthetic biology and genomics will have large parts to play as Wyss researchers come better to understand and manipulate human biology, which hopefully will pay off in terms of novel treatments for now-incurable diseases.

“We are collaborating with Don on enabling us to move from organs on chips to personalized and synthetic versions,” Church explains. He is planning on aligning his work on personalized genomics with the Ingber group to uncover how our genetics influence cell or organ functioning. This fits nicely with Silver’s vision of introducing her synthetic DNA into Ingber’s systems in a way that truly reflects what the Wyss Institute is all about: innovation through collaboration.

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