Biochemistry, Cell Biology
University of California, Berkeley
Dr. Rape is also the Dr. K. Peter Hirth Chair of Cancer Biology and a professor of cell and developmental biology at the University of California, Berkeley.
Ubiquitin-dependent Control of Cell Division and Differentiation
Michael Rape (pronounced RAH-puh) built his first laboratory when he was 12 years old. He wanted to understand how air pollution was harming the forests near his home in Bavaria. The budding biochemist constructed sealed chambers in his parents' basement and filled them with plants. He pumped in sulfur dioxide and other pollutants and measured their impact. Some of the plants died; the rest became much more susceptible to other toxins.
More than two and a half decades later, Rape runs a far more sophisticated laboratory at the University of California, Berkeley. The tenacity that propelled him to test the environmental impact of chemicals as a kid now drives him to understand a complex process critical to nearly all organisms: ubiquitylation. The term describes the attachment of a regulatory protein called ubiquitin onto other proteins. Ubiquitin tags communicate a wealth of information to the cell about what the tagged protein's fate should be.
At first blush, the process seems straightforward: add a protein to another protein. However, ubiquitylation is quite complex. The human genome encodes about 1,000 enzymes that either add or remove ubiquitin. Not only do these enzymes target different proteins, they also can influence where the ubiquitin is attached and how many ubiquitin tags are added or removed. These tags form a kind of secret code that allows for exquisite control of some of life's most fundamental processes, everything from cell division to transcription. "It's at the center of almost every regulatory reaction in the cell," Rape says. Cracking this code will lead to a better understanding of how these processes work and what happens when this important labeling system goes awry.
Rape first became interested in ubiquitin as a graduate student at the Max Planck Institute of Biochemistry in Germany. When he started his postdoctoral fellowship with Marc Kirschner at Harvard University in 2003, he expected to move beyond ubiquitin. However, his research with Kirschner revealed that ubiquitylation controls a far wider variety of processes than many scientists appreciated. Rape showed how ubiquitin can help kick-start the cell cycle after mitosis. He couldn't pull away. "I got hung up on ubiquitin," he says.
At Berkeley since 2006, Rape has developed novel screening tools to identify the ubiquitylation enzymes that are important for cell division and differentiation and pair them with the proteins they target. Matching the enzymes with their protein mates can lead to unexpected insights. For example, one pairing revealed that ubiquitylation regulates the size of transport vesicles, containers that can expand to carry large proteins such as collagen. When this process goes awry, the consequences can be devastating.
Abnormal ubiquitylation contributes to a variety of diseases, including cancer and Parkinson's disease. Rape hopes that his work in the laboratory will eventually translate into new therapies for patients. "Some of the best tumor suppressors and worst oncogenes are ubiquitylation enzymes," he says. "It's very clear that this pathway is important."
Scientific discovery can be an agonizingly slow process. But Rape rarely gets frustrated. "I have found something that makes me happy," he says. "I'm still as excited as I was as a 12-year-old."