B-sides of Research

Dr. Chuck Sanders

Located in Nashville, TN, the Sanders lab motto is a Patti Smith lyric: 

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"For beauty and the naked truth, it will cost you."

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As any PhD student can tell you, the cost of that first first-author publication is plenty, and it doesn't necessarily get any easier from there. However, talking to Dr. Sanders about his journey and life's work, you get the sense he's as excited today as he was on his first day in the lab. Chuck's lab studies the biophysical mechanics of membrane protein folding and misfolding using various biochemical techniques, as well as nuclear magnetic resonance (NMR) spectroscopy to investigate the molecular physics of protein interactions in solution. One of the most notable examples of protein misfolding contributing to a disease is the accumulation of amyloid-beta polypeptide in the pathogenesis of Alzheimer's disease, but you might be surprised to learn that over 60% of drug molecules target membrane proteins.  

 

Here,​ Chuck discusses the joys of growing up during the heyday of the Apollo space program, how a particular quality of the greatest jazz musicians is essential for the development of great scientists, and the importance of being a good neighbor in the world of science.

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The following interview took place on March 23, 2016. 

 

INTERVIEWER

Where’d you grow up?

 

SANDERS

Suburbs of Columbus, Ohio. 

 

INTERVIEWER

When did you know you wanted to be a scientist?

 

SANDERS

Three main influences:  The Apollo Space Program, backyard astronomy, and the desire to be a dinosaur when I grew up.

 

INTERVIEWER

Can you explain, in a few sentences, exactly what it is your lab is trying to accomplish?

 

SANDERS

Deciphering how defects in certain proteins, membrane proteins, cause (or at least contribute to) human diseases.

 

INTERVIEWER

What sparked the interest in your particular brand of research and what about it and the projects you work on has maintained it?

 

SANDERS

I got interested in membranes and membrane proteins as a grad student.  The disease angle came much later.  Long, boring story! 

 

INTERVIEWER

Did your early research involve NMR? How’d you become interested in the technique? Could you describe it in one sentence?

 

SANDERS

When I joined the lab in which I did my Ph.D. work I told my advisor (may he live forever) that I’d be happy to work on anything but NMR—it seemed so complicated! I quickly ate those words because NMR is such an incredibly versatile technique in which the atoms in the molecules being studied sing to you, declaring the nature of the molecular environment they dwell in.

 

INTERVIEWER

In approaching a topic/question to be investigated, what is your process in breaking down the complexities of a problem into the small incremental steps that lead to         discovery?

 

SANDERS

I take the time-honored approach of studying purified molecules in isolation (or as     complexes of two or three purified molecules) and then extrapolating the results       (not without peril) back to the vastly more complicated environment of the cell.

 

INTERVIEWER

What’s your favorite book?

 

SANDERS

Lord of the Rings.  But a pair of wonderful obscure books I like are Trees of Heaven and Hie to the Hunters by Appalachian writer Jesse Stuart.

 

INTERVIEWER

Do you have any favorite books on science? The history or application of?

 

SANDERS

Janet Browne’s two volume biography of Charles Darwin is pretty awesome… a very romantic story. I also liked The Emperor of All Maladies: A Biography of Cancer by Siddhartha Mukherjee. It was recently made into an PBS TV special.

 

INTERVIEWER

What is the future of science? It almost seems like music at this point, being broken   down into smaller and more specific sub-genres, and I’d say, to a certain degree, that further confuses the public majority. However, it also contributes to collaboration. What are your thoughts?

 

SANDERS

Hmmm…The cutting edge of science, at least on the biomolecular and biomedical       end of the spectrum, is becoming increasingly multidisciplinary where a wide ranges of approaches are applied to solve scientific problems.  I think that the willingness and talent to participate in multidisciplinary research will increasingly be required traits for scientists working at the cutting edge.

 

INTERVIEWER

I noticed that you have a page on your website devoted to US taxpayers. What is a        scientist’s responsibility to the public?

 

SANDERS

The public is willing to invest in research because they think they get something       for their money.  I think scientists need to view this investment as a sacred trust       and make sure that we conduct our work in a way that is consistent with public         expectations.  For my lab, the goal is to conduct our work in a way such that the         public gets the best possible return on their investments in terms of scientific             knowledge generated, new insights into disease mechanisms and treatments, new     technologies developed and disseminated, training of the next generation of scientists, transactions with companies from whom we purchase research supplies     and equipment, and gainful employment of project staff. To the extent we succeed I     think the public gets a good payoff!

 

INTERVIEWER

Bill Nye is back. Neil De-Grasse Tyson, Seth McFarlane, and Ann Druyan rejuvenated Cosmos. Nerds are cool. Science seems more prevalent in popular culture today. Do you pay any attention to that?

 

SANDERS

Not so much.  There is so little time…

 

INTERVIEWER

What role does politics play in scientific research?

 

SANDERS

I assume you means politics involving other scientists.  Scientific interpersonal           networks are just like other human networks—full of saints and sinners and everything in between.  Lots of politics! However, I will say that there are certain       areas of science, such as the peer review system for reviewing each other’s grants     and papers, where the degree of high-mindedness in which politics is set aside is truly admirable. I am generally proud of how scientists treat each other, especially     when it really matters.

 

INTERVIEWER

What about when it comes to Washington? What role does government play?

 

SANDERS

To be fair, I think both parties tend to be pretty supportive. Most scientists seem to     forget that. Except when it touches on hot button issues such as stem cell research,   I think both Democrats and Republicans are fairly supportive of science.

 

INTERVIEWER

Being a principal investigator and running your own lab, what’s your average day?

 

SANDERS

I suppose a typical day would be to have three hours of meetings (with students,         visiting speakers, lab staff, committees, etc.), spending half an hour doing editor’s       work for a journal, giving a one-hour lecture, doing another half hour of miscellaneous administrative work, taking care of various e-mail (another half hour) and several hours writing papers, grants, etc. All senior scientists pine for the good ol' days when they spent most of their days actually doing lab work!

 

INTERVIEWER

Grant writing is an art form. How has it changed in your career? Computer coding is now common in high school curriculums, how far behind are the technical science writing courses?

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SANDERS

I think of being able to write well as a general skill. Anyone who can write well can    write well as a scientist if they choose that path. Unfortunately, I think fewer and       fewer kids are learning to write well in high school and college. I am a big fan of a     liberal arts education, where learning to write is part of the required learning process.

 

INTERVIEWER

As a graduate student, what questions kept you up at night? As an experienced PI,     what questions now keep you up at night? 

 

SANDERS

As a graduate student, doing experiments often kept me up at nights! I would do   these 40 hour experiments and just stay at the lab the whole time. Sometimes I         would use a sleeping bag and catch an hour or two of sleep between data points.         Staying all night in the lab was also safer than departing the lab in the middle of the night…I once got mugged and beat badly walking to my car from the lab.

 

INTERVIEWER

Who and what inspired you as an early scientist?

 

SANDERS

Young people today do not have the privilege of growing up during the Apollo Space   program. What an amazing spectacle that was! Hand in hand with this was backyard (in my case front yard) astronomy…peering in my Sears Telescope in the depths of the sky and realizing you are literally looking into the past at light from stars and galaxies that had taken years and years to reach me. And early on there was also the hope that science could help me realize my dream of someday becoming a dinosaur.  My parents had told me I could be whatever I wanted to be when I grew up and it was very disillusioning when I finally realized that there are limits to everything.

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INTERVIEWER

Some of my favorite discoveries in science have been accidents. What’s yours? Have   you had any yourself?

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SANDERS

We were working with like 100 mutant forms of a membrane protein for several years when we realized that we could learn very little about the protein we were         studying using these mutants because most of them were prone to severe misfolding. This set my lab back a couple of years. But it also made me an expert on membrane protein misfolding, which led me to realize that literally dozens of diseases can be triggered by membrane protein misfolding…a major area of study in my lab for the past 15 years continuing through this day.

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INTERVIEWER

Do you pay much attention to scientific journalism? Do you think science is reported effectively in this country?

 

SANDERS

Not much time for that beyond Science and Nature, except for what I see in the local paper and in the New York Times. My impression is that there is a lot of wonderful journalism in this area, but that an awful lot of people are totally not interested for various reasons.

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INTERVIEWER

Taking a look at the budget, say science is involved in a primary against all the other sectors for discretionary spending dollars. What is science’s motto and running platform?

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SANDERS

The public’s investment in science is a very good investment for society. Many of       the “good” jobs in our society are science and technology-related and it is clear that     the public investment in scientific entities such as the National Science Foundation   and the National Institutes of Health translates into new companies, new technologies and therapies, and jobs.

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INTERVIEWER

How have the standards of publication changed from your first paper to your last?

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SANDERS

There is now a hysteria that there did not use to be about the need to publish in “high impact journals” (literally, journals with high impact factors…a quantitative           description of how often articles published in a particular are, on the average, cited by other papers). It used to be perfectly fine to publish all of one’s paper in high         quality journals with a rigorous peer review system for determining what gets published. Now, folks feel they have failed if they don’t get their papers in the high     impact journals.

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INTERVIEWER

Climate change denial, creationism, and anti-vax movements are constantly found in today’s print. As a research scientist, do you feel compelled to carry the flag of science against those who deny hard evidence?

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SANDERS

Sometimes, particularly if someone else brings up such a subject first, I’ll speak up.  I’ll also occasionally post particularly timely articles (about vaccines, for example) on Facebook. Unfortunately, people who deny hard evidence often do so because they fundamentally deny the merit of hard evidence. Not much you can do about that except be civil.

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INTERVIEWER

If you could live in another country and do what you do, where would it be and why?

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SANDERS

Well, I’m a homebody and so while I like to travel with family and friends I don’t really want to live anywhere except here in little ol' Nashville. But if I had to spend a year working somewhere else and didn’t want to take easy street (working in New Zealand, England, Ireland, Australia, or Canada—all wonderful places), I’d go to Japan, which is more like the moon than America.  Everyone should go to Japan before they die! No place like it.

 

INTERVIEWER

You’ve contributed to over 100 publications. You know a lot about a lot. In regards to the initial idea for a paper and writing it up, do you ever find yourself cheating now? Do your hypotheses begin to work against you once you’re so established?

 

SANDERS

What I would say is that one of the biggest challenges to a well-established scientist is the need to constantly reinvent yourself as a scientist so that your work does not go stale and become merely incremental. It’s just like the great musicians…. the true greats figure out how to reinvent themselves musically and can thrive for decades.  Other bands and solo artists never are able to move beyond their original sound and basically become a tribute band to themselves. A serious challenge for scientists.

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INTERVIEWER

What is or will be the biggest biological breakthrough in your time?

 

SANDERS

I am hoping and predicting it will be the discovery of life in outer space. As for           breakthroughs occurring during my life so far I think that the coupled discoveries of the roles of epigenetics and non-coding RNA in life as we know it are a pretty big dog deal, but these are harder to explain to non-scientists.

 

INTERVIEWER

Last, but not least: Beatles, Rolling Stones, Led Zeppelin, or Pink Floyd?

 

SANDERS

Led Zeppelin.

 

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Learn more about Dr. Sanders and his lab here. For those interested, the graphic above is the proposed model of interaction and conformational change between cholesterol and the C-terminal fragment of amyloid precursor protein, C99. To read more, click here. 

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Feel free to leave your thoughts on the interview in the comments section.