Ribosomes are responsible for the creation of all of the cell’s proteins. Some ribosomes are attached to the outside of a membranous organelle called the endoplasmic reticulum (ER), one of the main manufacturing facilities of the cell.  These ribosomes make proteins destined to be incorporated into the membranes of the cell. The created proteins must thread through the ER membrane by means of a protein-conducting channel and into the cell’s cavity, where they are then dispatched to other locations. Like every manufacturing effort, each component is important in the process.

As a graduate student, Dr. William “Bil” Clemons, was co-first author on a number of Nature papers describing the structure of the small ribosomal subunit. “Because the ribosome is a target for antibiotics, pharmaceutical companies spend a lot of money targeting the ribosome,” said Dr. Clemons, a recipient of a Burroughs Wellcome Fund 2005 Career Award in the Biomedical Science. “By building a 3-D picture of the ribosome, you can begin to understand, in a very detailed way, how the protein-synthesizing process works, and this improved insight holds potential applications for antibacterial design.”

In January 2004, Dr. Clemons, then a postdoctoral fellow at Harvard Medical School, was co-first author on a paper published in Nature describing the complex atomic structure of the critical protein-conducting channel in the ER membrane.  Dr. Clemons and his collaborators spent two years using X-ray crystallography to generate the vast amount of data that, when analyzed, revealed the channel’s structure. When the three-dimensional electron density map on his computer monitor finally showed the familiar spiral helices of a membrane protein, his part of the project fell into place.

Dr. Clemons and his colleagues have determined that the channel has an hourglass shape forming a hole in the membrane and a ring around the protein, allowing proteins to pass across the membrane while preventing leakage of other molecules from the cell.

“This has allowed us to propose models for how the channel operates and to answer many questions about its function,” Dr. Clemons said.

Dr. Clemons recalls always being interested in science. Even though his parents encouraged him to become a lawyer, when he received a National Merit Scholarship in high school, he opted to enter the biochemistry program at the Virginia Polytechnic Institute and State University. He went on to complete his Ph.D. in structural biology, working jointly at the University of Utah and the Laboratory of Molecular Biology, in Cambridge, England.

The multidisciplinary approach in structural biology appeals to Dr. Clemons. The variety of protocols, knowledge of tools, and different levels of problem solving keeps his interest peaked during the course of an experiment. “As a structural biologist, you have many different kinds of tools that you have to be able to use over the course of the lifetime of a project,” he said. “That is what keeps it exciting for me.”

Whether purifying proteins in order to grow crystals, analyzing X-ray diffraction patterns, or processing vast amounts of computer calculations required in the field, what Dr. Clemons finds most interesting is the image of the structure itself. “In the end, our data is not the most interesting thing in the world, because it’s all just numbers. But in the actual visual representation of that data there is a bit of artistry,” he said. “When you look at journals and see the pictures of structures, there’s actually an aesthetic side of it that I think is quite beautiful.”

Another aspect of the scientific endeavor that captures Dr. Clemons’s interest is mentoring. He recognizes that a number of minority groups are underrepresented in science, and he plans to establish programs in order to help overcome this problem.  “Without role models, it is no surprise that few minority students who make it to the college level choose science-related career paths,” he said. “Direct outreach programs by universities, working in conjunction with high schools on the state level, can encourage more minority students to pursue careers in research.”

In January 2006, Clemons began an assistant professorship in the Chemistry and Chemical Engineering Division at the California Institute of Technology, and he said he is looking forward to establishing his own research program. “Research skills alone do not make a successful principal investigator,” he said. “Leadership, communication, management, and team work are all factors. My success is as much a consequence of the people I’ve had the luxury to work with—and will continue to work with in the future—as it is due to my own talents.”

By Russ Campbell, communications officer at the Burroughs Wellcome Fund.