Emory Report
March 16, 2009
Volume 61, Number 23



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March 16
, 2009
Inside the protein factory

By Quinn Eastman

Christine Dunham is hunting for dinosaur bones. But she’s no archaeologist wielding a pick and shovel. She studies ribosomes, the protein factories inside every cell of every living thing. Ribosomes can be thought of as dinosaur bones because they begin to answer biology’s ultimate chicken/egg question: the origin of life.

If proteins are the machines that make our cells run and nucleic acids such as DNA and RNA store the blueprints, which came first? The answer biologists are finding more and more evidence for is: RNA.

The 1989 Nobel Prize-winning discovery that RNA can act as an enzyme, catalyzing chemical reactions and not just carrying information, has led scientists to postulate a primordial “RNA world,” before proteins took over and the genetic code came into being. Ribosomes, made mostly of RNA, are vestiges of this lost world, giving us hints of how those “dinosaurs” might have looked.

Dunham is part of a Emory/Georgia Tech/University of Georgia team studying the ribosome in “primitive” bacteria supported by a NASA astrobiology grant. Bacteria that live in extreme environments, such as hot springs or the Antarctic, are thought to give scientists a clue about what life could be like on Mars, since eons ago the Earth was probably much less life-friendly.

“Whenever a new organism is discovered — a bacterium, a butterfly, or a fish — the first thing anyone does is to sequence the largest part of the ribosome,” says Dunham, assistant professor of biochemistry. “It’s the most conserved gene in evolution, so it’s a guidepost for telling how that new organism is related to everything else.”

Dunham arrived at Emory in the summer of 2008 with her husband Graeme Conn, also a biologist who studies antibiotics and taste receptors. A varsity soccer player at Columbia University, she still plays several times a week around Atlanta.

Dunham came from the Medical Research Council’s Laboratory for Molecular Biology in Cambridge, England. Her signature achievement as a postdoctoral fellow there, working with Venki Ramakrishnan and colleagues, was to assemble a detailed picture of a ribosome. Her preferred tools are X-rays, which reveal the atomic details of how a ribosome’s parts are arranged. X-rays only reveal a ribosome’s or any other molecular machine’s secrets when the molecules are arranged in a crystal.

“A crystal structure is just a snapshot,” she says. “It doesn’t tell you how the machine moves. But we can use antibiotics to freeze ribosomes in one particular state and gain insight into that step.”

Thus, one side product of ribosome research could be new antibiotics. Ribosomes are particularly difficult to crystallize because they are large and have many parts compared to smaller protein machines. One of the biggest challenges in Dunham’s work is coaxing ribosomes into crystals of sufficient quality.

Dunham says she is excited to be at Emory because of recent investment in equipment that serves as the next best thing to a giant “atom smasher.” A growing group of Emory crystallographers such as Xiaodong Cheng are taking advantage to speed up their work.

To obtain the best data, crystallographers sometimes have to bring their crystals to sources of the strongest X-rays: synchotron accelerators such as the Advanced Photon Source at Argonne National Laboratory in Illinois or the European Synchotron Radiation Facility in Grenoble, France. When Dunham was working in Cambridge, she had to bring her carefully grown crystals on the train to Grenoble, just to have a clue how much and which kind of salt encouraged formation of the best crystal.

“Now, I can screen crystals here and pick only the best ones to take to the synchotron. And for many purposes, it’s possible to gather good data right here,” she says. “Many universities don’t have facilities like this.”

As an independent researcher, Dunham says she wants to investigate a feature of ribosomes found in retroviruses and bacteria called frameshifting, where a messenger RNA (instructions for making a protein) slips a step as it is being read. Frameshifting is required for HIV to make all of its proteins, for example.

“Being at a medical school makes you think more about the intersection between basic biology and medicine,” she says. “I think it’s a good change of pace.”