Chaperones for Our Cells

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All scientific discoveries, large and small, start with one common goal—to advance knowledge, be it about our bodies and health, our environment, or even our universe. But the most exciting discoveries, built on years of research and collaboration, fundamentally change how we understand our world.

In a special summer series, we'll talk with five Northwestern scientists whose work is already changing their fields, and could potentially change our lives. We start with Rick Morimoto, Bill and Gayle Cook Professor of Biochemistry, Molecular Biology and Cell Biology at Northwestern. 

When Morimoto thinks about proteins, he isn’t planning a meal of meat, chicken, or fish. The Evanston resident studies the way proteins in our cells keep those cells healthy. His work has changed our understanding of many age-related disorders including Alzheimer’s disease, ALS, and Huntington’s disease, and helped ignite one of the most promising areas in pharmaceutical research. We asked him to reflect on his work, and for some advice for those just starting out.

Rick MorimotoRick MorimotoWhy are proteins important?
Proteins are the backbone of all our cells, indeed all cells in all organisms. What interests us about proteins, given their diverse roles in all aspects of the functioning of the cell, is that they are involved in “quality control.”  Think of it this way: a cell is like a very sophisticated factory.

Imagine a factory – say one that makes iPads for Apple – that makes sure that each final product is beautiful and works perfectly. The factory has systems in place to be sure small errors do not become big problems down the line. Factories are very tuned in to quality control.

Likewise, our cells produce energy and convert nutrients into proteins, and they use specific molecules called chaperones to perform quality control. The key to good health later in life is for the quality control be done efficiently all along so small errors do not become big problems over time.

In my lab, we study these chaperones, just like the French word. And like any chaperone, their job is to keep others from misbehaving. Chaperone proteins detect, protect and prevent damage from accumulating in cells. Because when proteins misbehave, it causes all kinds of problems, including terrifying, neurodegenerative disorders like Alzheimer’s disease. What’s exciting about our work is that we are learning how to protect cells and prevent proteins from misbehaving by focusing on the efficiency of quality control chaperones.

Is there one discovery of which you are most proud?
I guess I would have to say that rather than a particular study or publication, I am most proud of a chain of events that began with an observation I made when I was first starting out as a young scientist (a recent PhD graduate, or post-doc) at Harvard. This observation was the basis of my being offered a faculty position at Northwestern, and 25 years later became the basis for a very promising therapeutic approach and the formation of a new biotech company founded in 2008.

How did you get interested in this topic, and what was that original observation?
I had a distinct ‘aha’ moment as a graduate student at the University of Chicago. It was during my second year, and a very prominent scientist named Matthew Meselson visited to give a lecture. (Meselson and a colleague named Frank Stahl discovered how DNA copies itself, or replicates.)

I was in the audience and he talked about something called the heat shock response in fruit flies. When these creatures get hot, it triggers a whole cascade of events in their genes. I sat there trying to imagine what a biological thermometer that did that would look like. How does the fly know that the cascade should begin? Eventually, I went to work for Meselson at Harvard, and what we learned is that the trigger is protein damage. The same thing happens in the brains of people with neurodegenerative diseases.

What is the therapeutic approach?
Creating a drug in the form of a pill that would prevent or delay further accumulation of damage to cells in diseases like Alzheimer’s or cataracts (night blindness). What compels us is that there is nothing out there at all for these terrifying neurodegenerative diseases that occur at increasing rates in Western countries and Japan. Now that we are living longer, we have things to worry about that didn’t exist in Shakespeare’s day.

Some scientists recall an event that made them fall in love with science. Did you have such an experience?
For me, it was more of a process than an event, something that I found on my own. I grew up doing science. My parents were very good about taking me to the library and leaving me there, and I say that in the most wonderful way. In the old days, there were stacks and I would find things – science books and journals that I would find on my own and read on my own. 

I went to Lane Tech for high school. I had this experiment I wanted to do, and I went to the University of Illinois, Chicago because I “needed” an electron microscope – 15 years old and I “needed” an electron microscope! I knocked on a door and one of the faculty members let me in and let me use his lab. And the best part was that he left me alone to do my project, and it opened up my world for me. These days, it wouldn’t happen that way, but we make room for young people to work in our lab so they can experience that thrill of discovery.

What advice would you give young people?

That’s easy. Always follow your dreams. Go for it with all the gusto and enthusiasm you have and never look back or give up. Take risks and be creative.

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