UTMB

Robert O. Fox, Ph.D.,
Professor

Faculty

Robert O. Fox, Ph.D.

About the Lab

Interview with Dr. Fox

– by Anasuya Roychowdhury, 3rd year BSCB Student

Science itself is a passionate expedition. It’s the passion that drives us; it’s the passion that motivates us; it’s the passion that moves us. Talking to Dr. Fox for two wonderful hours reminded me one good old quote "they may forget what you said, but they will never forget how you made them feel". That is the strength of passion! BSCB students are really fortunate to have such an enthusiastic, eclectic and a perfect scientific person like Bob as their teacher.

Dr. Fox came to UTMB in 1995. During the same time, the Structural Biology program was just being implemented and that appeared to him like a natural place to try and exploit all traditionally isolated techniques like X-ray, NMR and solution biophysics to answer specific questions. "That was a big plus", he continued, "also having a chance to build the X-ray component of the center was another big plus too". According to him the program was very well thought over in terms of what money would be needed for the right resources and the University has also been very generous in supporting that infrastructure of SCSB. "And so we built a very good program", he sounded very satisfied too. He also said, "We are very lucky to have good manager for NMR and X-ray equipments and people helping with the solution biophysics." In his own words, "That is important because these days I think directing to one focus of the biology is important but in order to do a good job you need to be able to master the underlying physical techniques .It is always good to have people who can train students in the technical area."

In his graduate studies, Dr Fox learnt crystallography from the people who were at the forefront of the field. He did his Ph.D at Yale University with Dr. Frederic Richards; Dr. Richards along with Dr. Hal Wyckoff, solved RNase S structure. RNase S was only third protein structure determined by X-ray diffraction of crystals after myoglobin and lysozyme and the first crystal structure in US. "The equipment we used to do the diffraction at Yale was built by Wyckoff himself", recollects Dr. Fox. "When I did this work it was just computer graphics that was being applied in order to study the protein. So Richards went to Oxford and he built an optical comparator, also called Richards box. It was basically a stack of plexiglass sheet and they were contoured like the geographic survey map by electron density and the stacks. You can look through the stack and see the protein structure fitted into the electron density. Just like you do electron density fitting these days in computer. That was very interesting!" I was simply spellbound to hear that experience from him and said "So you have experienced the evolution of the field!" He laughed and said "Well, not entirely, but yes, so far"!

According to Bob the development of X-ray diffraction is the most significant scientific observation which helped him to think his scientific problem at fundamental level. When I asked about his scientific idol, his first expression was "I respect so many people." Then he mentioned about his Ph.D mentor Dr. Fred Richards who was very special in his time and he has been a wonderful figure to him too. He also got to know Dr. Jeremy R. Knowles (famous chemist and protein engineer later on became the dean of Harvard University). "When I was in Oxford I had a chance to meet Noble laureate Dr. Dorothy Hodgkin too", he proudly said. "She was really a very brilliant scientist who solved the structure of insulin and worked with Dr. John Demmond Bernal and took some of the first X-ray photographs of the first protein crystals. Dorothy was awarded the Nobel Prize in Chemistry in 1964 for determining the structure of Penicillin and vitamin B12 which were very hard problems", he added. Recounting his Oxford experience he said "I gave a seminar in Oxford and at that time Dr. David Philips was the head of crystallography. He also was Science advisor to the Prime Minister so he was barely in the panel but when I went to give the seminar, I looked up and David was in the first row. Dr. Jeremy R. Knowles and Dr. R.J.P. Williams (a very renowned chemist) were also there! I thought ‘Ohh boy what kind of audience I have to deal with!’ So I started my introduction and when I was getting into the material, I looked up and saw Dr. Dorothy Hodgkin entering the seminar hall. She sat down and apologized for being late!!! That was quite an enjoyable time". As Bob recollected his good old memories, we were listening to his experiences like a fairy tale.

The best way is to keep the student’s enthusiasm and encourage them to solve the problem and think about the problem, to own the problem. If you own the problem, you won’t lose the enthusiasm."–Dr. Fox,
on motivating students.

Dr. Fox himself has many gems of contributions in his academic career. During his thesis Bob solved the crystal structure of alamethicin the polypeptide that made ion channel in cell membrane. He also made a model of the ion channel and proposed the mechanism of the voltage gated ion channel. In his words, "Structural modeling was fun and was kind of wide open territory. It was something what everyone wanted to know. This work was published in Nature and has been cited close to 500 times." Then his work on how the SH3 domain recognize proline rich sequences with Dr. W. Lim and Dr. Fred Richard was also very important as it revealed how a conserved binding face can be used to recognize peptides in different orientations.It was also published in Nature and has been cited around 500 times as well. Later on, his group also developed chemical cleavage technique based on reactive oxygen species to map the backbone fold of a protein in a non-native state. This technique also reveals regions of non-native structure. In addition to their own research, several other scientific groups were also benefited by this technique which brings a lot of satisfaction to Bob. In the next few years, he really wants to focus on synthetic biology, where protein engineering gives insights into basic science.

When I asked him on what he expects from a good student, he replied that a good student should be enthusiastic, and passionate. He/she should enjoy science, and think deeply about a problem and should own the problem. He further added, "I think things go best when my scientific goal matches with my student’s, so that we can develop goals and strategies together." Further, he also added, "A good student is someone who keeps asking questions, is willing to know more and knows that he/she needs to know more." I was curious to know from Bob about how he motivates his students when things do not turn out the way it is expected, for which he replied, "I listen, and I am always a participant. The best way is to keep the student’s enthusiasm and encourage them to solve the problem and think about the problem, to own the problem. If you own the problem, you won’t loose the enthusiasm." He further added, "You can take risks as a graduate student, as a post doc, as a junior faculty member or as a senior faculty member and each of these have their own level of danger. However doing something hard for a graduate student involves least risk. So, if a student finds anything interesting, he/she should go for it without worrying too much. Sometimes even if you can’t solve the problem, you can always gain knowledge on how to attack the problem logically inspite of the yield being low."

Bob considers that all the students belonging to the BSCB program are in the right program for the future biological research. He believes that biology will become progressively more quantitative and mathematical. So if a student has the necessary background of mathematics, physics and chemistry, that insight will help him/her to provide an approach towards solving the biological problem.

It is said that "a great teacher is a great artist and teaching might even be the greatest of the arts since the medium is the human mind and spirit." In his every comment Bob appeared to me as a great teacher with whom you can share your knowledge, with whom you can instigate your passion for doing science. As happens sometimes, a moment settled and hovered and remained for much more than a moment and in brief that moment we get memories that last a life time. The interview with Dr. Fox reminded me that again.