Donald Gray, Ph.D., professor of the Department of Molecular and Cell Biology, decided in college that most areas of science were to his liking.
He graduated with degrees in chemistry, physics and math, which serve as the foundation for his career in research. He got his M.S. and Ph.D. degrees in molecular biophysics at Yale University.
“Many students coming in as undergraduates are headed to medical school. If they don’t get into medical school, they think, ‘Maybe I’ll go to graduate school and do research.’ For me, it was the other way around.
“For a while I was a premed student in undergraduate school, but I found that I liked studying physics and math so much that I had to give up courses required as the premed prerequisites. I wanted to learn more physics and math. And so, if I were not in research, maybe I would be in medicine, which would be just the opposite of many of our current students,” Gray said.
The Department of Molecular and Cell Biology, when it began as a unit of the Southwest Center for Advanced Studies, was set up during the period when DNA and genetic regulation and the nature of the gene were being discovered. The department successfully emphasized the molecular aspects of biology, he said.
Gray said he was among the first to arrive after the campus became part of the U.T. System, in 1970, and was provided a new instrument called a circular dichroism, or CD spectropolarimeter. It measures the difference in absorbance between left and right circularly polarized light. Gray’s interest: studying the form and function of deoxyribonucleic acid and DNA protein complexes.
“We had the ninth Cary Model 61 CD spectropolarimeter made and set up a laboratory to do this work, which was rather unique at the time. That’s what attracted me. UT Dallas was a place to do research. The institute paid $60,000 for the CD system, which involved a computer with only 8k of memory. It was a large investment at the time, but it was the beginning of 19 years of National Institutes of Health (NIH)-funded research and grants awarded by the Welch Foundation, which still continue.
“Organic molecules often have a structure,” he went on to explain, “so that the molecule is not the same as its mirror image, sort of like your right hand and your left hand. All biomolecules have this property of chirality. And the technique we used was circular dichroism spectroscopy to study the chirality of molecules, especially nucleic acids. At one point we had an NIH-funded consortium involving a group at Los Alamos National Laboratory that had the expertise to synthesize long DNA and RNA polymers of defined sequences, our group at UT Dallas that determined their CD properties, and a lab at Purdue University where polymer structures were determined by fiber X-ray diffraction."
Experiments involving nuclear reactors
One of his major experimental successes came in the late ‘70s and early ‘80s. Gray and his wife, Carla W. Gray, Ph.D., visited Grenoble, France, to do some special research on the structure of a DNA-protein complex – research that could only be conducted with the help of the neutron beams from a nuclear reactor.
Gray’s wife came with him to The University of Texas at Dallas, and for many years was a research scientist and senior lecturer in the biology department.
“We used a technique called neutron diffraction, which was a very intensive type of work. Nuclear reactors produce neutrons, and we worked at reactors in Grenoble, France, and later at Brookhaven National Laboratory in this country. Beams of neutrons are available from a nuclear reactor, and you have to put your sample, in this case DNA-protein complexes made by filamentous viruses, into the beam of neutrons to obtain information about the locations of the DNA and the protein in the complex. It’s an expensive type of research to carry out and there is little margin for error because beam time is very limited,” he said.
Model of a short section of a DNA-protein complex made by certain filamentous viruses. The DNA (red dots) is shown surrounded by copies of the protein (blue and green figures). Taken from Olah et al., J. Molecular Biology, vol 249, pp. 576-594 (1995).
"In our work we were able to show that the DNA was inside of a layer of protein in these complexes, the opposite from the structure that others had published. In the 1990’s we refined this result combining X-ray scattering data obtained at Los Alamos National Laboratory and new data from neutron scattering,” Gray said. (See accompanying figure.)
He has been studying the physical chemistry of DNA and DNA-protein complexes for more than 30 years. He led the first outside user group to measure CD spectra on the biology beam line of the National Synchrotron Light Source at Brookhaven National Laboratories, defined the theoretical limitations on the information about neighboring nucleotides that can be obtained from the study of nucleic acid sequences, and, together with his most recent students, spent a decade studying the control of gene expression in living cells by modified DNA molecules called antisense DNA drugs.
“With respect to our current research, we are studying the human replication protein A, or RPA. There is a class of proteins called single-stranded DNA binding proteins, which carry out essential functions in living cells. These proteins are involved in replication, or reproduction, of DNA.
“The DNA-binding domains of RPA are similar to those of many other single-stranded DNA binding proteins, including ones made by filamentous bacterial viruses, which we’ve studied a great deal.
“We plan to identify DNA sequences and DNA structures that are preferred binding locations for RPA. The identification and study of DNA binding sites for RPA should lead to a clearer picture of the role RPA plays in processes such as DNA replication and repair,” Gray said.
Head of the department
Gray was department head from 1989 to 1995 and again in from 2004-2007. He compared the two stints.
“In 1990, we became a four-year undergraduate institution and that was a whole new challenge for us to set up a four-year undergraduate program. Fifteen years later we had a much more mature undergraduate program. That’s a big difference,” he said.
New facilities and programs are the other change.
“Now we are looking forward to having new space and facilities, which we desperately need. We now have the Sickle Cell Disease Research Center, under its director, Betty Pace, M.D., which we didn’t have at all, even an inkling of, 15 years ago. There’s an emphasis on biotechnology with new master’s programs in Biotechnology and in Bioinformatics and Computational Biology. So the whole outlook is more interwoven, and the challenge is to figure out what best we can do to help the university reach a new level of research status,” Gray said.
He said he has a high opinion of his colleagues.
“The research-intense efforts that a faculty member has to be involved in means that everybody is expected, on the one hand, to be an independent spirit, to be able to direct the work of students and post docs. At the same time, there’s strength when there’s a group of people who can communicate and work together.
“We are a small department, so the people who collaborate and work together are in relatively small groups right now. Our goal would be to expand those groups and have more interactions both within the department and outside the department at other schools like UT Southwestern Medical Center,” he said.
Independence is expensive
Today, Gray said that in addition to teaching students molecular and cell biology, he tries to get them to think critically and be independent thinkers.
“It takes a while for students to be independent, to start asking and answering their own questions, instead of relying on some mentor or some textbook. That’s what we are trying to teach students to do.
“It’s time-consuming, and it’s a big effort, helping students become their own thinkers.
The advantage is long-term in society. The pay-off is only years later when the students think of things and ways of doing things that we would never have thought of. But the initial cost is not trivial in terms of time and effort,” Gray said.
Over the years he said he has mentored 26 master’s students and 16 Ph.D. students.
“So I think we have done a good job with the students who have come to us and have graduated from UT Dallas. And eventually that will help the university and its reputation in the long run. The quality of our graduates – their competitiveness and success – I think is something that will be appreciated only years later, perhaps in another generation.”
- Updated: September 16, 2008
