Probing Protein Processes: A Conversation with Rebecca Voorhees

Rebecca Voorhees, a newly appointed assistant professor of biology and biological engineering, has been awarded a Pew-Stewart fellowship to examine how proteins are created and destroyed.

Protein complexes are intricate biomolecules, used in essentially every task carried out by cells. Rebecca Voorhees, assistant professor of biology and biological engineering and Heritage Medical Research Institute Investigator, is fascinated by how proteins are made, the cellular quality control mechanisms that destroy defective or unnecessary proteins, and how these mechanisms malfunction during diseases like cancer.

Voorhees joined the Caltech faculty this year and most recently was named a 2018 Pew-Stewart Scholar. We sat down with her to discuss the life cycle of proteins, the state-of-the-art microscopes crucial to her work, and life back in the United States after 10 years in England.

What do you study?

Broadly, we are trying to understand two related areas of biology: protein biogenesis—how proteins are made, how they get to the right places in the cell, how they are assembled—and what happens when these processes fail. How does the cell recognize when something has gone wrong? How does it degrade a bad protein to prevent disease?

Proteins can't be seen with regular microscopes. What kind of equipment do you use to study them?

To look at protein structure, our laboratory uses X-ray crystallography—where you shoot X-rays through a crystallized sample and observe how they scatter—and cryo-electron microscopy, or cryo-EM. Cryo-EM allows us to take detailed images of a protein at very, very cold temperatures. Caltech has actually just set up a new facility with two cryo-EM microscopes, which is really critical and exciting for my research and for others at Caltech interested in protein structure and molecular mechanisms.

Are there specific kinds of proteins you focus on?

We are particularly interested in membrane proteins, which make up a fairly large proportion of proteins made in the cell. Membrane proteins have large stretches of hydrophobic, or water-repellant, amino acids because they ultimately end up in the cell's membrane, which is hydrophobic as well. The challenge is, cells have to make these proteins in an environment full of water. How does the cell deal with these hydrophobic sequences? How do you get them to the right place? What happens when these processes fail?

When a membrane protein fails to make it to the membrane, it can create aggregates, or clumps, of proteins within the cell. Protein aggregates are associated with diseases like Parkinson's and Alzheimer's. 

What did you do leading up to Caltech?

I grew up in Chicago and went to Yale for my undergraduate degree in biophysics and biochemistry. Then I was in England for 10 years, for graduate school and a postdoctoral fellowship at the Medical Research Council Laboratory of Molecular Biology. I just moved back this past summer.

Are there things you miss about England?

I never felt like I was really British, even though I had been there for a long time. So being back in the U.S. is like coming home and I'm really excited about it. But it does take some getting used to—especially the sunshine and warm weather.

One thing I will try to bring with me from England is that we would always have tea and cake every afternoon with the lab. It was a really informal way for people to chat, sometimes about science and sometimes not. It fostered a lot of casual interactions and discussions that it's difficult to engineer in any other way. So, I'm hoping we can at least partially implement something like this in my lab. 

What's an interesting fact about you that people might not know?

I played intercollegiate water polo during undergrad at Yale. It got me into the habit of waking up really early, so most days I'm up at 5 a.m.

Written by Lorinda Dajose

Lori Dajose
(626) 395-1217