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.
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. 4-5 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, Slovenia, and
Imperial College 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.
“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.
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
available for other researchers to add and retrieve information. This
library will be similar to the bacterial Registry of Standard
Biological Parts housed at MIT.
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.
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.
The iGEM team received support from the departments of electrical
engineering and molecular biology, the Center for Innovation in
Engineering Education, the School of Engineering, the Office of the
Provost, the Princeton Institute for the Science and Technology of
Materials and the National Science Foundation.
