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Two faculty will benefit from Keck awards to do research

Joanna Wysocka

Karl Deisseroth

Stanford University has received two million-dollar grants from the W.M. Keck Foundation for projects aimed at using light to control a variety of cells and exploring how specific enzymes help embryonic stem cells turn into adult cells. The beneficiaries of the grants are Karl Deisseroth, MD, PhD, assistant professor of bioengineering and of psychiatry and behavioral sciences, and Joanna Wysocka, PhD, assistant professor of chemical and systems biology and of developmental biology.

Deisseroth will use a $1.5 million science and engineering grant to advance his research on controlling cells with pulses of light. The technique, which has found enthusiastic users across the country, shows promise as a tool for improving disease research and could lead to new therapies for certain ailments.

Last year, his research group demonstrated the ability to genetically engineer brain cells, called neurons, so that they could be selectively turned on in the presence of blue light, or off in the presence of yellow light. Now Deisseroth, leading a team from several departments within the Schools of Medicine and Engineering, has made two key improvements that he will employ with the funding from Keck.

One improvement is that he has begun to apply the technique to cells other than neurons. Most notably, he has found that he can engineer different types of heart cells to be responsive to light. This allows researchers using the technique to study and control cells implicated in some cardiac abnormalities, such as arrhythmias, in which the heart beats erratically.

With another recent advance, Deisseroth's team has figured out how to engineer cells to be stimulated, rather than turned off, by yellow light. Now researchers can conduct experiments in which they cause two different types of cells in a neural circuit to turn on—one with blue light, the other with yellow. Such experiments could yield insights into diseases in which more than one type of cell is suspected of playing a key role.

Wysocka received $1 million as one of five Keck Young Scholar in Medical Research awardees this year nationwide.

Wysocka's work involves DNA—the threads made of four different molecular units variously arranged to encode the genes that make up all living organisms. Specifically, she studies how DNA is packed and organized to activate or silence genes, independent from the specific DNA sequence. These DNA sequence-independent effects on gene expression are the topic of the new and burgeoning field of epigenetics.

A close look at our DNA reveals that it is thoroughly covered with proteins that act like miniature spools for the DNA "thread." Wysocka is especially interested in understanding how interactions between these proteins and DNA influence genes, turning them on or off at various times during an organism's life.

The Keck award will allow her to study how members of a pivotal group of enzymes turn genes on during the transition from embryonic stem cells to mature cells. These enzymes, the Trithorax-related methyltransferases, carry out a specific chemical alteration—the addition of a methyl group—at specific locations on one of the predominant proteins spooling the DNA. That alteration occurs when virtually any human gene is activated.

Wysocka said she hopes her findings will contribute to efforts to use stem cells to repair damaged tissues and organs. The work is also likely to shed light on the origins of many diseases, including cancer.

Based in Los Angeles, the W.M. Keck Foundation was established in 1954 by the late W.M. Keck, founder of Superior Oil Co. The foundation's grant making is focused primarily on pioneering efforts in the areas of medical research, science and engineering. The foundation also maintains a Southern California Grant Program that provides support in the areas of civic and community services with a special emphasis on children. For more information on the foundation, visit http://www.wmkeck.org.