Contacts:
Stephen Ekker, (612) 626-4509, [email protected]
David Largaespada, (612) 626-4979, [email protected]
Scott McIvor, (612) 626-1497, [email protected]
Perry Hackett, (612) 624-6736, [email protected]
Deane Morrison, University News Service, [email protected], (612) 624-2346
Teri Charest, Academic Health Center Communications, [email protected], (612) 624-4604
U of Minnesota Wins One of Two Grants from Beckman Foundation
MINNEAPOLIS / ST. PAUL--The University of Minnesota is one of two universities in the nation to receive the first Arnold and Mabel Beckman Foundation Technology Development Grant, which will provide up to $2.5 million over the next five years for the development of "Sleeping Beauty," a novel system for transferring genes into vertebrate cells. The university, along with the University of Texas at Austin, was selected from more than 90 applicant institutions, each of which was permitted to submit only one project proposal.
Sleeping Beauty is basically a strand of DNA that, under the direction of an enzyme (called the Sleeping Beauty transposase), is very good at inserting itself into chromosomes. By attaching other genes to Sleeping Beauty, scientists can use it to ferry those genes into the nuclei of cells and from there into chromosomes. Its name comes from its origin as an obsolete gene in fish that was "awakened" and modified to work as a transfer agent of genes. That work was done by Perry Hackett, professor of genetics, cell biology and development at the university, who is a co-investigator on the grant. Other co-investigators, all in the same department, are assistant professor David Largaespada and professor Scott McIvor. The principal investigator is assistant professor Stephen Ekker.
"Right now, Sleeping Beauty is like the Model T of gene transfer systems," said Ekker. "We will use the grant funds to improve the system so that it transfers genes more efficiently. After five years, we hope to have the Ferrari of gene transfer."
Ekker plans to optimize Sleeping Beauty as an agent of gene transfer in fish, with a goal of identifying the functions of genes whose functions are currently unknown. In those experiments, Sleeping Beauty would insert itself into working genes, disabling them. By observing what structures or functions are impaired as a result, Ekker could identify the function of the genes. For example, if Sleeping Beauty were put into fish eggs and those eggs grew into fish that had tiny eyes, then a gene for eye structure would have been found. Since the basic genes of fish and humans are similar, this work is expected to help identify genes that guide human development and whose loss or malfunction can cause birth defects.
Largaespada focuses on using Sleeping Beauty to identify genes associated with cancer, particularly genes necessary to prevent cancer. Working with mice, he hopes to find genes that, when disabled by Sleeping Beauty, result in tumors. By finding the place Sleeping Beauty has inserted itself into a mouse chromosome he can then localize the gene. Again, the similarity of mouse and human genes will make this work applicable to humans. If, say, a gene whose disablement is associated with a colon cancer can be found, then therapies could be directed at getting that gene working again.
McIvor will concentrate on using Sleeping Beauty for gene therapy. Using mice as a model, he will work on ways to precisely determine the locations on chromosomes where Sleeping Beauty inserts itself, and in what quantities. For example, suppose a gene to counteract a genetic defect could be transported into human cells by Sleeping Beauty. Before such a system could be used on patients, one would have to make sure the gene was being delivered to a chromosomal location where it could stay active and that enough cells were receiving the therapy for it to make a difference to the patient's whole body.
Hackett will work on getting Sleeping Beauty to work better as a whole. Sleeping Beauty is essentially a gene for a "molecular scissors"--an enzyme that snips the Sleeping Beauty gene out of a chromosome and splices it into another one. The bulk of the Beckman grant will be used to improve the enzyme and the gene so that this cutting and splicing will work better.
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