A Princeton-led team of students who are programming stem cells to treat diabetes ranked third in the world in a recent competition to build working “genetic machines” out of DNA building blocks.

Team Princeton placed first among all 19 U.S. participants and third among all 33 teams internationally at the third annual Genetically Engineered Machines (iGEM) Jamboree, held on Nov. 4 and 5 at the Massachusetts Institute of Technology. The team also won second place honors in the “Best Real World Application” category. The top finishers internationally were from the University of Ljubljana, Slovania, and the Imperial College of London.

The Princeton team demonstrated the early components of a system that would instruct embryonic stem cells from mice to turn into insulin-producing pancreatic cells of the sort that are missing or damaged in diabetics. These genetic circuits could ultimately be used for human embryonic stem cells, probably with few, if any, modifications.

Senior Ritu Kamal and junior Sanjiv Goli (foreground) prepare to extract some DNA

“It’s really exciting to think about the potential implications for the treatment of diabetes,” said Ron Weiss, an assistant professor of electrical engineering who runs the University’s summer iGEM program in collaboration with Ihor Lemischka, a professor of molecular biology.

Team Princeton was one of only two competitors to work with mammalian cells, as opposed to simpler bacterial cells, and the only team to work with mammalian stem cells. The 13 students on the team — eight Princeton undergraduates, three students from Cornell University, Michigan Technological University and University of Maryland, and two high school students — were led by Priscilla Purnick, a postdoctoral research associate in Weiss’ lab. Electrical engineers Sairam Subramanian and Ernesto Andrianantoandro, along with molecular biologist Christoph Schaniel, assisted Purnick in the team’s instruction.

A major portion of their work this past summer was devoted to the creation of mammalian “biobricks,” small pieces of genetic material that can be assembled to create working circuits. These circuits instruct cell behavior, for instance by directing them to differentiate into specific tissue types. Based on these efforts, the Weiss and Lemischka labs, in collaboration with MIT, are jointly establishing an open access library of mammalian biobricks that will be accessible for other researchers to add and retrieve information. This library will be similar to the bacterial Registry of Standard Biological Parts housed at MIT (http://parts.mit.edu).

Purnick said that isolated pieces of the insulin-producing system are now working and that the entire system could be operational in the lab within a year.

Per their design, the stem cells grow and multiply until they sense, based on sufficient levels of a chemical they produce, that it is time to turn into pancreatic beta cells. This self-regulating system could be a significant breakthrough for the treatment of diabetes if scientists transplant similarly engineered stem cells into a human pancreas and allow them to make insulin.

The researchers’ work on engineered cell-to-cell communication and differentiation into a variety of tissue types has implications for the treatment of numerous conditions that have stymied modern medicine, including traumatic spinal cord injury and neurodegenerative disease.

The iGEM team received support from the departments of Electrical Engineering and Molecular Biology, the School of Engineering, the Center for Innovation in Engineering Education, the National Science Foundation, the Office of the Provost and the Princeton Institute for the Science and Technology of Materials.

Four Princeton undergraduates are completing independent research based on the iGEM projects. In the meantime, Purnick and Weiss are preparing to assemble Princeton’s 2007 iGEM team, which will continue the research on directed differentiation with a goal of demonstrating a fully functional system at next year’s Jamboree.

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    Electrical and Computer Engineering