Templeton foundation supports Yukiko Yamashita’s pioneering work on germline immortality

Whitehead Institute Member Yukiko Yamashita has received a grant from the John Templeton Foundation to explore the importance of maintaining ribosomal DNA repeats in the “immortality” of germ cells, which pass the genome on to an organism’s progeny. Yamashita’s work on this fundamental question of life could open whole new paths for mitigating the cell-aging process—and could lead to new treatments for cancer, which may hijack the germline’s mechanism of immortality. 

“Organisms and cells age and eventually die, but germline cells—the precursors of egg cells and sperm—effectively continue from generation to generation,” explains Yamashita, who holds the Institute’s Susan Lindquist Chair for Women in Science. “One of biology’s biggest mysteries is exactly how germ cells avoid aging.”

Yamashita’s Templeton-funded study—entitled, Germline immortality: transgenerational maintenance of unstable genetic elements—focuses on one of the most vulnerable elements of the genome: the large number of tandemly repeated DNA sequences that occur within the sections of the genome that support ribosomal function. (Ribosomes are large enzymes that translate messenger RNA into proteins.) These sections, known as “rDNA,” can have hundreds or even thousands of repeats.

The large number of repeats within rDNA is necessary for normal ribosomal function; but it is also highly susceptible to copy number loss—and, therefore, to cellular dysfunction. In previous studies, Yamashita’s lab had already begun to explore the mechanisms that maintain rDNA copy number and to trace what happens when rDNA copy number is not maintained. 

“Our initial work found that if rDNA copy number is not maintained, animals decline in fecundity over several generations and the lineage goes extinct,” says Yamashita, who is also professor of biology at Massachusetts Institute of Technology and an Investigator of the Howard Hughes Medical Institute. “Based on those findings, we have proposed that rDNA copy number is a critical heritable feature of cellular aging, and that transgenerational maintenance of rDNA copy number is fundamentally important to survival of an organism’s germline.”

With the Templeton Foundation’s important support, Yamashita anticipates gaining foundational knowledge about the mechanisms of rDNA copy number maintenance. “This new knowledge may allow us to uncover a critical parameter in predicting an organism’s lifespan and, possibly, discover a means to prevent cellular aging,” she says.

“Also, because the very same mechanisms likely allow tumor cells to proliferate unlimitedly, we may find a new, ideal target of cancer treatment.”

Founded in 1987, the John Templeton Foundation supports research on subjects ranging from black holes and evolution to creativity, forgiveness, and free will; and it encourages civil, informed dialogue among scientists, philosophers, theologians, and the public at large. With an endowment of $3.9 billion and annual giving of approximately $140 million, the Foundation ranks among the 25 largest grantmaking foundations in the United States.