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Meet the Community: Paula Cramer
By Carol Curzon Morton
As a scientist and a seasoned traveler, MCB postdoctoral fellow Paula Cramer anticipates the unexpected—whether it is an unexplored neighborhood or an uncharted protein function. But even she was surprised to be awakened in the hotel room by early labor pains last year after a visit to an Andy Warhol exhibition at the new home of the Museum of Modern Art in Brooklyn. This Memorial Day weekend, Cramer, her husband, and son are returning to New York to celebrate Manuel's first birthday. Even though a new baby is keeping Cramer closer to home these days, her horizons continue to expand in other ways. "My stay here has provided me with the ability to think of biological problems with no boundaries," Cramer says. "Really, any approach you would like to apply to a problem can be done." In the lab of Tom Maniatis, Cramer is investigating a group of three gene clusters that make proteins known as protocadherins. Originally, their unusual transcription behavior had attracted the attention of the Maniatis lab. By deft alternative splicing maneuvers, the genes can make more than 50 variations on their proteins merely by mixing and matching exons at one end of the mRNA. Now, Cramer and her colleagues want to know what the proteins do. They show up during development and in the adult on cell surfaces in the brain and nervous system, including synaptic junctions, where one neuron connects with another. It might be just an accident of evolution that a few versatile gene clusters can code for such a large group of proteins, but the researchers suspect the explosion of diversity of these genes may have some purpose. For example, the genes are found only in vertebrates, whose nervous systems are famously complex, and not in simpler organisms where as few as two neurons can handle a basic task, such as laying an egg. "We are thinking they could help establish the specificity of synapses," Cramer says. "The remarkable variety of expressed protocadherins could be a sophisticated way of helping neurons commit to their specialized function and location." So far, the investigations in the lab remain works in progress. "We are developing tools to observe the expression of these proteins," Cramer says. "We have developed antibodies against them and are starting to use them against each of the variants of one cluster called alpha. Together with other molecular tools, that will let us know which variants are expressed in different cells, and how many are expressed per cell. Their location says something. Their abundance says something. And when they are expressed in development says something. It will all help understand their function." Like the protocadherins she studies, Cramer also mixes and matches a diverse assortment of research techniques. In contrast with her graduate student days in Argentina, she can easily tap into a world-class array of specialized expertise in nearby labs. For example, she needed to master a technique for engineering bacterial artificial chromosomes, also known as BACS. Only a few labs were working with the technique.
After her postdoctoral fellowship, Cramer plans to return to Buenos Aires. She wants to give something back to her country’s free public education system, which transformed her parents’ generation of mostly impoverished European immigrants into a professional middle class and continues to school their children from kindergarten to doctorate. Unfortunately, national support for research is less reliable. "It’s such a different system in every aspect," Cramer says. "Here, I would interview with a given number of universities, which would likely provide the lab space, some start-up money, and a decent salary." In Argentina, Cramer will aim for a stable mix of local and international funding. For example, the Howard Hughes Medical Institute funded the lab she worked in for her PhD, and a Hughes grant supported a friend who returned to an academic research position in Argentina nearly two years ago. In the meantime, the parenting demands of Manuel, her year-old son, have curtailed some of the diversions she and her husband enjoyed when they first moved to Cambridge, such as attending author events at the local bookstores, seeing movies, visiting museums, strolling around Walden Pond and Southern Vermont, skiing in New Hampshire, and traveling to other North American cities, such as Chicago, San Diego, Miami, and Montreal. On the other hand, Cramer appreciates the cozier nature of Cambridge and Boston. "It’s nicer to walk to the lab and not to have to commute," says Cramer, who lives in Harvard-owned housing. Conveniently, Manuel’s day-care center, also sponsored by Harvard, is just across the street from their apartment.
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