The sequencing of the fruit fly genome several years ago has given researchers powerful new tools: Today's lab fruit flies come in hundreds of different varieties, each with a different gene knocked out. Dr. Lilach Gilboa of the Biological Regulation Department zeroes in on the ovaries of fruit fly larvae to unveil the basic principles that regulate normal organ development – principles that could provide insights into cancer development as well as suggest ways to make stem cell therapies more effective.
Some questions she asks are: How does one cell type turn into another? On the other hand, how and why do "originator" cells such as stem cells avoid differentiating into various cell types? Primordial germ cells – the earliest versions of the cells that will eventually become eggs or sperm cells – migrate to special niches in the ovaries during development, where they then differentiate into a type of stem cell called an adult germ line stem cell. This change originates in alterations to the germ cell environment, so the study of niche development is key to understanding these cells.
What role do these "helper" cells play in the lives of stem cells? Gilboa seeks out the messages passed between various specialized niche cells and the primordial or stem cells, directing their development. By screening mutant ovaries for abnormal differentiation of their germ cells, she and her team were able to identify around 30 genes involved in producing stem cells and keeping them from differentiating.
Gilboa suspects that some aspects of cancer growth may involve a breakdown of messages similar to those sent between ovarian stem cells and niche cells. Cancer cells communicate with their surroundings, often using the "language" of development to "trick" their neighbors into supporting them – producing new blood vessels, for instance, to nourish them. Revealing the mechanisms of the healthy crosstalk in development may thus help researchers understand why some cells end up breaking their own internal rules and abetting cancer growth.
Another question Gilboa asks is: How do the developing larvae keep on top of inventory, maintaining a certain number of stem cells, but no more? Here, too, she has found a genetic factor that may help the body keep these cells in balance. This could be crucial to designing effective stem cell therapies. Stem cells have not yet lived up to their promise as cures, and Gilboa thinks part of the difficulty may be that the body's mechanism for regulating cellnumbers causes the introduced cells to be rejected. If this mechanism could be manipulated, the extra cells might be more easily absorbed. Cancer growth may be tied, as well, to a failure of the mechanisms for regulating cell numbers.
Without Compromise
Dr. Lilach Gilboa grew up in a small village in Israel. She always wanted to be a scientist; she chose to study at Tel Aviv University, however, because it allowed her to take humanities courses in addition to her scientific research. She is especially interested in the history of science and enjoys reading when she finds time between running a lab and caring for her young daughter.
After completing postdoctoral research in the U.S., Gilboa joined the Weizmann Institute as a senior scientist. "The Weizmann Institute enabled me to come back to Israel without compromising my scientific research. Whether I succeed or not depends entirely on me."
Dr. Lilach Gilboa's research is supported by the Helen and Martin Kimmel Institute for Stem Cell Research; the Willner Family Center for Vascular Biology; the Abisch Frenkel Foundation for the Promotion of Life Sciences; the Abraham and Sonia Rochlin Foundation; the Center for Health Sciences funded by the Dwek Family Biomedical Research Fund and the Maria and Bernhard Zondek Hormone Research Fund; and Lois Rosen, Los Angeles, CA