Researchers at the University of Michigan Life Sciences Institute are creating a legion of fruit flies to advance our understanding of Down syndrome, thanks to funding from the Klatskin-Sutker Discovery Fund.
The cause of Down syndrome — an extra copy of chromosome 21 — has long been known. But much less is known about which genes drive each of the specific conditions that affect patients with Down syndrome. And without knowing which genes are causing a problem, researchers cannot determine which genes to target therapeutically.
“There are about 200 different genes on chromosome 21,” explains Bing Ye, Ph.D., research associate professor at the LSI and the recipient of this year’s Klatskin-Sutker award.
“So, the challenge in the field is to identify the genes that contribute to these different diseases within in Down syndrome. It’s not an easy problem to solve.”
With the Klatskin-Sutker funds, Ye plans to develop many different models of Down syndrome in Drosophila melanogaster, or fruit flies. Because fruit flies have a very short life span, multiple generations can be created within a matter of weeks. And their well-mapped genome allows researchers to study the roles of specific genes — which leads to a better understanding of how those genes function in humans.
Ye’s goal is to create approximately 60 different genetic lines of fruit flies — each with an extra copy of a different gene found on chromosome 21 — to begin determining how each of the genes contribute to the various aspects of Down syndrome. His lab has prioritized these 60 genes because they are expressed in the nervous system, Ye’s area of expertise.
The Klatskin-Sutker Discovery Fund was established through a generous gift from the Klatskin and Sutker families to support this type of innovative, early-stage research that has potential for high impact on human health.
“This project ultimately could impact our understanding not only of Down syndrome as a whole, but of many different human diseases,” says Deborah Klatskin.
“It is precisely the type of research upon which successful translational and human-health research must be built, and we are thrilled to be able to support it,” adds Burton Sutker, M.D., who also serves on the LSI Leadership Council.
Once the various lines are established, Ye will make them available to other researchers who are interested in studying defects associated with Down syndrome — which can range from congenital heart failure to neurodegeneration — in other organisms and eventually in humans.
“This research provides a novel and powerful approach for investigating the molecular mechanisms that underlie diseases in Down syndrome, and it is a great example of the power of model systems in biomedical research,” says Roger D. Cone, Ph.D., the Mary Sue Coleman Director of the LSI. “By narrowing the pool of genes to investigate, the Ye lab will help make Down syndrome research in mammals more manageable and efficient.”
Ye is also the U-M Burton L. Baker Professor of the Life Sciences and an associate professor of cell and developmental biology at the U-M Medical School. His lab at the LSI investigates neuronal development and defects that lead to brain disorders, such as the dysregulated gene expression seen in Down syndrome. Ye's previous research demonstrated that, in fly models, an FDA-approved cancer drug was able to reduce the extra branching of neurons associated with Down syndrome and other similar conditions.