Science took hold of Brenda Schulman early. She still remembers when her high school biology teacher revealed the myriad roles of ATP (adenosine triphosphate) in a cell. While still in high school, Schulman also had a chance to work in a university lab that was exploring how genes are turned on. That made her wonder about the impact of their structure on the process. Before she finished high school, Schulman had won the national Bausch & Lomb Science Award, given to high school students who have demonstrated unusual academic achievement in science.
Schulman is still curious about biological structure, and she integrates knowledge of structural biology, biochemistry, cellular biology, and genetics to address a central question in biology: How can cells respond quickly to the changing demands and cues of their environments?
Often, a cell can react most rapidly by tweaking an existing protein, rather than by taking the time to make a new one. For this, cells employ a protein tagging system to reassign, redeploy, or disintegrate other proteins. The tags carry out vital signaling for immune responses and cell division. Several of the tagging proteins are deregulated in cancer, neurodegenerative diseases, and viral infections.
Schulman studies how tagging proteins that are members of the ubiquitin-signaling family are chosen for their specific jobs. Figuring out those differences will help define the roles of various family members and the molecular basis of recognition, and make it easier to develop therapeutic agents.
Schulman has largely solved a central and long-standing question of how activators of ubiquitin-like proteins function in such specific ways. A complex series of reactions are catalyzed by a cascade of enzymes called E1, E2, and E3. The enzymes find, prepare, escort, and attach ubiquitin or one of its relatives to its assigned target molecule. The ubiquitin tag triggers a specific cellular activity, such as one of the steps of cell division.
The ubiquitin pathway has many E1 and E2 enzymes, hundreds of diverse E3 enzymes, and thousands of targets. In the first step of recognition, Schulman found that a specific E1 first distinguishes the closest molecular relative of ubiquitin from its cousin by recognizing one small difference. The ubiquitin-like molecule ultimately sets off a cascade of biochemical reactions to eliminate the molecular brake on cell replication. In the absence of this brake, cell replication could get out of control, and if left unchecked, could cause cancer.
She plans to study how the ubiquitin family regulates the timing of cell division by activating and degrading molecules.
