Understanding Thomas Steitz’s work with ribosomes

Michael Schreiber

In the time since Thomas Steitz ’62 became Lawrence University’s first Nobel laureate “for studies of the structure and function of the ribosome,” Steitz has been celebrated at home and abroad. Some of his most recent recognition has come from Lawrence, as Science Hall is to be renamed in Steitz’s honor.
However, the importance of Steitz’s work has been, at least to some extent, lost in the hype. Just why are “studies of the structure and function of the ribosome” important?
According to Ron Peck, assistant professor of biology, ribosomes are centrally important structures in biology.
“Ribosomes are a group of molecules that act as the factories in cells,” said Peck. “As you likely learned in any biology class, proteins are the main action molecules of life.”
Peck elaborated on the function of ribosomes, saying that they “carry out the last steps in taking information in DNA and turning it into protein.”
Thus, said Peck, “DNA gets all the hubbub,” but “DNA is useless without ribosomes.”
Because of their great importance to all life, studies involving ribosomes have many implications for human health.
“Ribosomes are the targets for many antibiotics,” said Peck. “Some antibiotics bind to and inhibit [or reduce the functionality of] ribosomes in bacteria, but will not bind to ours.”
Peck noted that many disease-causing, or pathogenic, bacteria are resistant to the antibiotics that are currently available. The lack of effective treatments for staph infections and tuberculosis caused by resistant strains of bacteria creates a need for new antibiotics to be developed.
According to Peck, targeting bacterial ribosomes specifically during drug development allows for drugs to have “selective toxicity” in bacteria, toxicity which might be effective against current resistant strains of bacteria.
However, it is difficult to design drugs that target bacterial ribosomes without knowing the ribosomes’ structure, and according to Peck, this is where Steitz’s work becomes important.
“[Steitz’s] work in determining the structure of the bacterial ribosome is in many ways analogous to Watson and Crick’s elucidation of the structure of DNA,” said Peck.
Peck expanded on the importance of Steitz’s work, applying it directly to the field of drug engineering.
Peck noted that by determining the structure of the bacterial ribosome, Steitz has enabled scientists to “design molecules, which we [later] call antibiotics, against spots on the ribosome that are different” from the spots that current drugs target.
Therefore, Steitz’s work “helps us in the ongoing war between pathogenic bacteria and antibiotics,” Peck said.
Peck noted that Steitz’s work also provides insight into how life originated.
Said Peck, Steitz has worked to “identify what it is about RNA molecules [that is] required for making proteins.”
Besides its implications for drug development and the origins of life, Peck said that Steitz’s work is notable because it is “very bold to try to figure out large, complex structures” using Steitz’s technique of x-ray crystallography.
According to Peck, the scope of Steitz’s research is analogous to trying to figure out how an entire automobile works at once. Someone less ambitious might just investigate a portion, such as the wheel, but Steitz has taken on the whole car at once, “including the complicated engine,” Peck said.
Steitz’s ambitious investigations using x-ray crystallography involve firing x-rays at a crystal of a compound and using a detector to collect the x-rays as they are deflected in a characteristic pattern by the crystalized substance of interest.
Peck noted that x-ray crystallography presents two major challenges to scientists.
“First, and most challenging, is figuring out a way to get your [substance of interest] to crystalize,” Peck said.
Second, after firing the x-rays and analyzing the deflection pattern, the scientist must “figure out and use complex math to calculate back from the [x-ray] pattern to determine the position of atoms within the crystal,” Peck said.
Peck compared this second challenge to using sonar; however, unlike sonar, the x-ray beams are deflected instead of bounced back, so there are many more variables to account for.
Although Peck highlighted the importance of Steitz’s research, he also noted that Steitz’s work should not be thought of as entirely groundbreaking.
“I can’t say that no one else thought this question [of the ribosome’s structure] was important, but it’s been a long sought-after question,” said Peck.
The work with ribosomes is far from over. Peck noted that, so far, only the structure of ribosomes belonging to simple life forms lacking a nucleus – life forms called prokaryotes – has been determined. Future scientists will try to solve the structure of the human ribosome, and once that feat has been accomplished, a whole new age of drug discovery will dawn.
With the structure of the human ribosome solved, scientists will finally be able to directly compare the structures of prokaryotic and human ribosomes. Said Peck, “That’s the next big hurdle.

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