Life as he knows it
In the 1980s, Dr. Johann “Hans” Deisenhofer and two colleagues at the Max Planck Institute of Biochemistry in Germany used X-ray crystallography to determine the 3D structure of a photosynthetic reaction center isolated from a bacterial cell membrane. The scientists received the 1988 Nobel Prize in Chemistry for their work, which helps explain the detailed mechanism of the first steps of photosynthesis. Plants and bacteria use photosynthesis to convert light into chemical energy in a reaction that sustains life on earth. During more than three decades at UT Southwestern, Dr. Deisenhofer has solved the structure of many more proteins and helped establish UTSW’s Structural Biology Laboratory core facility. A Regental Professor and Professor Emeritus of Biophysics and in the Cecil H. and Ida Green Comprehensive Center for Molecular, Computational, and Systems Biology, he agreed to share his thoughts with In Pursuit.
Was there any particular hurdle you overcame in determining the first structure of a membrane protein using X-ray crystallography?
The greatest hurdle to overcome was a firm belief in the community of molecular biologists that membrane proteins could not be crystallized. That made it difficult to get funding for such projects. The specific funding mechanisms of the Max Planck Institutes made it possible to go forward despite skepticism. It was my friend Dr. Hartmut Michel who, with support from his mentor, Dr. Dieter Oesterhelt, succeeded in growing well-ordered crystals of a bacterial photosynthetic reaction center. In retrospect, this achievement was decisive for our success.
Did anyone tell you it could not be done?
Yes. At first we met with skeptical comments, but after a period of steady progress, we became convinced that we would come to a result.
In 1991 you were quoted as saying you hoped someday we could predict the structure of a protein from its amino acid sequence. Have we done that? Is it still a hope?
A lot of progress has been made in this respect. In part, this was aided by the ever-increasing number of known protein structures, which allowed structure prediction based on homology between amino acid sequences. Also, there were a few success stories on computationally simulating the folding of small proteins, with results very similar to experimentally determined structures.
Also in 1991, you said progress in this field would closely parallel the development of computers. Did your prediction come true?
The example of computationally simulating protein folding shows this point. Success was only possible after developing a special computer that was about 100 times faster than any computer on the market at the time.
How did the Nobel Prize change your life? Your career?
My career was pretty much set by my move to UT Southwestern in January 1988. The Nobel Prize brought many changes in the ways people looked at me, especially soon after it was announced. The first sign of recognition by the University was a named parking spot. Then came lots of invitations, both in the U.S. and overseas. There were also attempts to attract me back to Germany. A lasting effect was a significantly increased salary.
How has the imaging field changed over that time? What do you foresee as its future?
In the 1980s, it took several years to determine the crystal structure of a big protein, even after it had been crystallized. In the meantime, due to improvements in X-ray sources, computing hardware, and especially software, this time has shrunk to weeks – or even days in some cases. Then came the breakthroughs in cryo-EM (electron microscopy), removing the need to grow crystals and adding the possibility to study structurally inhomogeneous samples. Nevertheless, in the end, I think advances in structural biology will happen mostly in computers.
Tell us about your childhood, your family, and what influenced you to become a scientist.
I was born during World War II on a farm in Southern Bavaria. According to local tradition, I was destined to take over the farm from my parents. However, I never showed any interest in farming, and when I was 13, my parents and teachers helped me to get into middle school and high school. The most influential book I read as a teenager was Frontiers of Astronomy by Fred Hoyle. This book made me want to become an astronomer, but when the time came to decide on a field of study, I chose physics and was accepted as a student at the Technical University of Munich. The reasons to choose physics were many. In retrospect, the most important of these was that it provided a broad foundation that allowed me to continue in directions I did not know about when I started. Also, at the time I entered the University, Dr. Rudolf Mössbauer, who became famous for the effect named after him, had moved from the United States back to the Technical University. The resulting rise in student applications was sometimes called the “second Mössbauer effect,” and I was part of it.
What drew you to the field of biophysics?
The decision to move into biophysics came during my work for a master’s degree in experimental physics at the Technical University of Munich. My mentor, solid-state physicist Dr. Klaus Dransfeld, was asked to give a course in biophysics and immersed himself deeply into the subject. His intense interest became infectious. I next found a place to work for my Ph.D. in a newly opened laboratory for X-ray crystallography of proteins in the Max Planck Institute of Biochemistry in Munich.
What brought you to UT Southwestern?
In the summer of 1986, I received an invitation from Dr. Joe Sambrook, then-Chair of Biochemistry at UT Southwestern (at the time called The University of Texas Health Science Center at Dallas). Joe had started to establish a structural biology unit with the recruitment of Drs. Elizabeth Goldsmith and Steve Sprang, and was looking for additional candidates. Apparently, he had heard from friends in Europe that I was looking for a new position. I visited in the fall of 1986 and in January 1987. My impression was very positive; also, the prospect of becoming an Investigator in the Howard Hughes Medical Institute (HHMI) was an attraction.
How did you meet your wife, Dr. Kirsten Fischer-Lindahl, UT Southwestern Professor Emeritus of Immunology?
Kirsten had moved to Dallas from Switzerland in 1985 to join the faculty of the Department of Microbiology, with a secondary appointment in Biochemistry, and was one of the University’s first HHMI Investigators. Dr. Sambrook asked her to show me around Dallas during my first visit. After my move to Dallas in 1988, we fell in love and married in 1989.
How has UT Southwestern changed since your arrival? What remains the same?
UT Southwestern has grown to about three times its size of 1988. But, as far as I can tell, the support for basic biological science has remained as strong as always.
What are your personal plans for the future?
I want to spend much of my remaining health span dividing my time between Dallas and our mountain retreat in Jackson Hole, Wyoming (summer and winter), travel occasionally, and remain connected via the internet with UT Southwestern and to as many friends and relatives as I can.
How would you describe yourself? To what aspects of your personality do you credit your success?
I am an introvert with a strong desire to understand the world around me, and especially the things I am doing.
What are your hobbies?
My main hobbies are listening to classical music, going for walks, and downhill skiing.
Is there something people might not know about you?
Maybe, but if so, I would like to keep it that way.