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Biologist David Shub Explains the Inexplicable

by Greta Petry

David Shub
David Shub

There has been a vast change in the biological sciences since Professor David Shub joined the University at Albany faculty 33 and a half years ago.

“Many of the fields we studied back in the ’70s are not fashionable now,” he said. Most of the scientists with whom he studied have switched from their original research areas to newer fields where research funding is more readily available.

Shub has adapted well to the changes, using his “contrarian attitude” to ask new questions in hypothesis-driven experiments. “I look for the parts that don’t fit,” he said. “Many unanswered questions remain.”

New fields like genomics require the collection of massive amounts of data.

“Understand that it took five years to crack the genetic code for one bacterium. The Human Genome Project, which was supposed to take 15 years, took fewer than ten. Now complex genomes are being completed in one month,” Shub said.

With this tremendous amount of data flooding the field, the need exists for the next generation of trained Ph.D.s in biological sciences who can do “small science” or hypothesis-driven experiments to make the most of that data, he said.

Today Shub has a grant of about $50,000 per year from the Northeast Biodefense Center, one of eight NIH-funded Research Centers of Excellence for Biodefense and Emerging Infectious Diseases Research, to study how the tables can be turned on the anthrax bacterium.

“Viruses and the organisms they infect have been co-evolving since the beginning of evolution. It is an arms race between the host and the parasite that infects it. All cells, even bacteria like anthrax, have a series of viruses that infect them. Why not try to design drugs that mimic how the virus kills the bacterium?” Shub said.

The UAlbany biologist, who was prominently featured in a Q. and A. article in the November issue of Current Biology, was department chair for three years before being succeeded by Al Millis in 2002-2003. In this regular feature, the journal seeks out the views of a prominent scientist on issues in science.

“I was really surprised and honored to be asked,” Shub said.

This past academic year Shub taught Genetics 212 for undergraduates and half of an advanced undergraduate course, Molecular Biology 312. The day he was interviewed by Update, he was also in the midst of preparing questions for a final exam.

Shub, who did his undergraduate work at Columbia and earned a Ph.D. in biophysics from the Massachusetts Institute of Technology, is applying for NIH funding to resume his ongoing work on introns and selfish DNA. Before becoming chair, he was funded for work in this area through just over $300,000 a year in grants from NIH.

In the Current Biology Q. and A., Shub was asked: Why have you spent your entire career studying bacteriophages? [A bacteriophage is any virus that is parasitic upon certain bacteria, disintegrating them.] Generally speaking, it’s because he likes to examine unexplained phenomena.

“I started this work in response to Marlene Belfort’s and her colleagues’ published results in 1984 and 1985, describing the discovery of self-splicing mobile introns in phage T4,” he said.

Belfort, a professor of biomedical science at the School of Public Health and a member of the National Academy of Sciences, studies the biology of introns, dynamic sequences that interrupt genes and disrupt the flow of genetic information. Introns exist in almost all life forms and are removed by a process called RNA splicing. Through her research, Belfort seeks to answer questions about how introns evolve and function, and explore how they may be used in biotechnology.

In his response, Shub said, “Marlene Belfort offered to collaborate on this totally unexpected finding, providing my lab with a wonderful problem that we have been exploring ever since.”

Shub delights in finding the piece that doesn’t fit. “If it violates a rule, something is wrong,” he said. This is what makes science interesting.

“The odd thing about bacteriophages is how frequently they surprise us,” he told Current Biology. “For example, the large subunit topoisomerase gene of phage T4 (and some close relatives) is split into two cistrons, one of which requires the ribosome to make a 50-nucleotide jump during translation.” Cistron is another word for gene. Shub said it is “bizarre” for a ribosome to behave in this manner and although the experimental evidence is clear, “It should NOT be able to do this.” Shub consulted with a leading scientist in the field, who agreed with the validity of the evidence, even though current ideas about ribosome structure suggest it should be impossible.

“When something happens like that, you gotta love it,” Shub said.

Over the years, Shub has seen the number of professors in his department decline from 36 to about 25 today, even as molecular biology gained prominence over organismal biology.

“It is ironic that with the approach of excellent facilities that allow us to attract exceptional faculty and build the department back to where it was, now budget constraints for the University as a whole make that unlikely, at least in the short term,” he said.

“The challenge is for planned growth in good times and how to manage during an era of shrinking budgets. I wish the next president well in solving this problem because it is one of the major issues the new administration will face,” Shub concluded.