Bil Clemons: Following Scientific Curiosity

By Kimberly Smith

Bil Clemons: Following Scientific Curiosity

"I found a passion for both biology and chemistry in high school and thought, Well, that must mean I'm a biochemist! Luckily my naïve thought was correct. I am a biochemist," says Bil Clemons,

Ph.D. He's a professor of biochemistry at the California Institute of Technology (Caltech) in Pasadena, where he's been teaching and running a lab for nearly 20 years.

Dr. Clemons doesn't remember a time when he wasn't interested in science or curious about the world. "I think, fundamentally, that's what being a scientist is: being curious about how the world works," he says. As a child, he'd open seed pods to see the insides or take toys apart to see how their tiny motors worked. He couldn't always figure out how to put the toys back together, though, which led to his parents warning him not to ruin his siblings' new toys on Christmas morning.

After finishing high school, Dr. Clemons went to Virginia Polytechnic Institute and State University (Virginia Tech) in Blacksburg to study biochemistry. Virginia Tech offered a great biochemistry program, a scholarship, and opportunities to get involved in research, which made the decision to attend there an easy one.

When he learned from his undergraduate adviser that he could pursue a Ph.D. at no cost -- and that he could even earn a paycheck while

studying -- Dr. Clemons chose to go to graduate school. He was interested in structural biology (the study of how biologically important molecules are structured to understand how they function) and joined the lab of Venki Ramakrishnan, Ph.D., at the University of Utah in Salt Lake City. Soon after, the Ramakrishnan lab, including Dr. Clemons, moved to the Medical Research Council Laboratory of Molecular Biology in Cambridge, England. With Dr. Ramakrishnan, Dr. Clemons studied the structure of ribosomes, which are molecular complexes of proteins and RNA that make proteins in cells. He contributed to the research for which Dr. Ramakrishnan would later share the 2009 Nobel Prize in chemistry.

After studying ribosome structures, Dr. Clemons turned his attention to what happens after proteins are made, especially how they get to where they need to be. The secretory pathway moves newly made proteins from the endoplasmic reticulum to the Golgi and then to the cell membrane to be embedded within it or released outside the cell. Dr. Clemons focused on learning more about the steps of the secretory pathway during his postdoctoral research at Harvard Medical School in Boston, Massachusetts, where he received mentoring from Tom Rapoport, Ph.D., and Stephen Harrison, Ph.D.

An Ever-Evolving Lab

The research projects in Dr. Clemons' lab at Caltech are eclectic, which he says is a result of his curiosity. "I get the most motivation from pursuing questions that my team and I are excited about. Because of that, our focus is constantly evolving as people come and go," he says. "If you took a snapshot of our work every 5 years or so, you might wonder if it's even the same lab."

One of the longest-running themes in the lab is studying how membrane proteins, such as tail-anchored proteins, are made and shuttled to the membrane. Tail-anchored proteins are important for many activities, including receiving signals from other cells and releasing molecules outside the cell through exocytosis. Dr. Clemons' team wants to understand the unique steps needed for these proteins to be successfully delivered to the membrane. In addition, they're determining the structures of the proteins involved. To do so, they use a variety of techniques, including X-ray crystallography and cryo-electron microscopy (cryo-EM). The team has also been exploring how this process differs among organisms by comparing the pathway in yeast, the parasite Giardia, and humans.

Another ongoing research topic in Dr. Clemons' lab is studying how bacteria build peptidoglycan, which is a large sugar molecule that typically makes up their outer layer. Some antibiotics target enzymes in the pathway that makes peptidoglycan because human cells don't produce it, so the medicines are highly specific for bacterial cells. However, not every enzyme in this pathway has been fully characterized. Dr. Clemons is working to identify and structurally characterize the enzymes, which could be targets of new antibiotics one day.

Giving Back

Dr. Clemons believes that his mentors' guidance has contributed to his career success, and he hopes to impact his students' lives in a positive way in return. "Some of the future world problem-solvers are here at Caltech. One of the joys of my job is shaping their paths, providing opportunities for them that may not be there otherwise, and helping them see more in themselves than they do," he says.

Outside of the lab, Dr. Clemons is a science program officer at the Chan Zuckerberg Initiative (CZI). He is responsible for ensuring that CZI research grants are awarded to researchers from a diverse set of backgrounds, that the work they do broadly benefits the public, and that the results of those projects are widely accessible. "All of these things are important pillars for the way we think about addressing the problems of the future," he says.

Dr. Clemons' research, along with that of his collaborator Michio Kurosu, Ph.D., receives NIGMS funding through grant R01GM114611.

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