A team of ISU researchers is working to unlock the mysteries of ribosomes in order to develop new forms of antibiotics.

“Bacteria are becoming more resistant to the antibiotics we have,” said Dr. Malhar Gore, staff physician at the Thielen Student Health Center.

He said the overuse, under use and misuse of antibiotics can also contribute to this problem.

Gloria Culver, assistant professor of biochemistry, biophysics and molecular biology, and her research team hopes to help alleviate this problem through their research of ribosomes.

Harry Noller, professor of molecular, cell and developmental biology at the University of California-Santa Cruz, said understanding how a ribosome works and having knowledge of its three-dimensional molecular structure can help design novel antibiotics.

Ribosome are responsible for decoding the sequence of amino acids of mRNA during protein synthesis, essential for life. According to Ohio State University’s cancer handbook, growth factors, hormones, enzymes and muscles are all proteins.

“If the ribosomes can’t make the right proteins, the organism cannot function,” Culver said.

Scientists began studying ribosomes several decades ago, but this line of research went out of vogue until just recently, she said.

“If we can understand ribosome assembly, we may be able to identify new targets for antibiotics,” Culver said.

Although ribosomes are composed of two asymmetric components, the small and large subunits, Culver said the team’s research deals primarily with the 30S subunit.

The group is conducting several types of experiments, and one of the most significant discoveries so far is the role of the DNAk chaperone system. DNAk is a gene found in the E. coli bacteria. Chaperone is a type of protein.

“The implication of DNAk in ribosome assembly is very exciting to us because previously no extra-ribosomal assembly factors have been identified,” said Jennifer Maki, research assistant and graduate student in biochemistry, biophysics and molecular biology. “The DNAk chaperone system has already been very well characterized in its role in protein folding.”

There are three components in this chaperone system, DNAk, DNAj and GrpE.

“When DNAk recognizes unfolded portions of proteins, it binds to them and allows proper folding to occur by preventing the proteins from sticking together,” Maki said. “DNAj regulates DNAk’s protein-binding and ATP hydrolysis. GrpE speeds up the release of ADP, a product of ATP, and inorganic phosphate from DNAk.”

These steps form a cycle.

“DNAk will bind, release, bind, release, etc. until the protein is folded,” Maki said.

Maki said researchers used E. coli to study the DNAk chaperone system.

“[Test tube] reconstitution [of E. coli] requires heat. But [in nature] E. coli does not need these high temperatures to assemble its ribosomes. It can grow at lower temperatures too,” she said. “Therefore, something must facilitate the [natural] assembly of ribosomes.”

The experiments showed DNAk could be one of the factors that facilitates the natural assembly of ribosomes.

“Many more experiments will be conducted to determine the mode of action of the DNAk chaperone system in this process. It is new ground, so we are trying to carefully pick the process apart so we can understand each step” Maki said.