Peter Baumann spends a lot of time looking at beginnings and endings: beginnings in an unusual form of lizard reproduction and endings in the telomeres that keep a cell healthy by protecting the tips of its chromosomes. He explains his…
Peter Baumann spends a lot of time looking at beginnings and endings: beginnings in an unusual form of lizard reproduction and endings in the telomeres that keep a cell healthy by protecting the tips of its chromosomes. He explains his interest in these seemingly unrelated research paths by saying that he does his best work when he steps off the well-trodden road. "You can often make a significant contribution by just stepping onto the white part of the map and looking to see what's there," he says. Although Baumann first discovered science through the naturalists and field biologists he watched on television as a child in Germany—especially David Attenborough and Konrad Lorenz—he veered toward biochemistry and molecular biology in college. As a graduate student at the Imperial Cancer Research Fund in London (now Cancer Research UK), he began his work on DNA repair. With mentor Stephen West, he was the first to characterize the Rad51 protein, which human cells use to mend potentially fatal DNA breaks without losing genetic information. During his postdoctoral fellowship in the lab of HHMI Investigator Tom Cech at the University of Colorado at Boulder, Baumann found himself drawn to the way that telomeres maintain their integrity by hijacking DNA repair mechanisms. He began focusing on the interface of DNA repair and telomere maintenance, and one finding in particular caught his attention: proteins believed to be involved in finding and initiating the repair of double-strand DNA breaks were also associated with telomeres. How can a protein vital for promoting repair also be involved with telomeres, which help prevent chromosome ends from fusing, he asked. The answer came in a telomere-binding protein he found in human cells and fission yeast. He named it POT1 (for protection of telomeres). It binds to telomeres, regulates their length, and protects them. When the protein is missing in fission yeast, the cells' chromosomes can unravel and fuse into a disastrous tangle. And, Baumann found, the protein also is responsible for regulating the activity of telomerase—the enzyme that maintains the telomeres and is key to a cell's health. Too little telomerase can result in tissue degeneration; too much can lead to overgrowth and cancer. In 2002, Baumann moved to the Stowers Institute for Medical Research in Kansas City, Missouri, where he now concentrates on telomere protection and maintenance. He has isolated in fission yeast the gene for the telomerase RNA subunit that contains the template for telomeric DNA, which provides him with a tool to study telomerase assembly and control. "At the time, it seemed like we were just going to replicate an experiment that had been done with budding yeast, etc. We didn't expect it to be anything big," he says. But they found a pathway that hadn't been seen or even thought about in other organisms, which helped his group determine how organisms assemble and regulate telomerase. "Over the last five years, we have evolved into a lab that studies the biogenesis of telomerase," he says. Such research, he hopes, will lead to therapeutics that curb cancer and other diseases—either by inhibiting telomerase activity in cancer cells or by boosting it in disorders involving insufficient telomerase, such as diabetes and a rare congenital disease called dyskeratosis congenita. And the lizard reproduction work? Baumann's naturalist interests sucked him into whiptail lizard biology. "It started with a conversation about the herpetofauna of New Mexico," he says, and the discovery that unisexual lizard species were the result of cross-species sexual reproduction, which started them out with a great amount of genetic diversity. Baumann found himself wondering how these all-female species produced eggs that developed without being fertilized by male sperm. "It started out as a Saturday afternoon project, and I had to promise the leadership at Stowers that it would not interfere with my main research program," he says. Those Saturday afternoons led to significant insights. In a paper published in Nature in 2010, Baumann describes how whiptail lizards double their chromosomes prior to meiosis—the cell-division process that produces an egg cell with only half the number of chromosomes. During sexual reproduction, the egg is fertilized by a sperm cell with the complementary number of chromosomes. But in whiptail and other unisexual species, the doubled chromosomes pair up and recombine. "In these lizards, the offspring are identical to the mother, but each individual is endowed with a high degree of heterozygosity," he says. This allows the lizards to retain genetic diversity—and to survive and thrive in a changing environment. The whiptails have since become a second major focus of Baumann's lab. He believes future research will reveal a more comprehensive picture of how extensive the genetic diversity of this all-female species really is and a deeper understanding of the molecular and cellular underpinnings of how it maintains that diversity.