Innovative Molecular Biologist Joins Cancer Biology Department

By Eric Sauter

The Scripps Research Institute has named Min Guo as an assistant professor in the Department of Cancer Biology on the Scripps Florida campus.

Guo, who was a senior research associate in the Schimmel-Yang lab at Scripps California before joining Scripps Florida, researches cellular mechanisms involved directly in protein production, which could lead to novel treatments of melanoma, the most lethal form of skin cancer.

Guo, who is 31 and lives in Jupiter, officially joined Scripps Florida this month.

"We're extremely pleased that Min Guo chose Scripps Florida and the Department of Cancer Biology," said John Cleveland, chair of the department. "His work in the intricacies of protein production and the role of enzymes in directing that process is both original and highly relevant to the development of possible cancer treatments. We fully expect that his contributions to science and to our department will be significant, and we want to offer our warmest welcome."

Guo received his bachelor's degree in Biology and his Ph.D. in Structural Biology from the University of Science and Technology of China (Hefei, People's Republic of China), before his postdoctoral work in the Schimmel-Yang lab.

"I'm honored to be joining the Cancer Biology faculty on the Scripps Florida campus," Guo said. "I appreciate the collaborative spirit at Scripps Research in both California and Florida and I'm looking forward to working with all of my new colleagues in Cancer Biology – and in other departments as well."

Going After Melanoma

For a number of years, Guo's research has focused on the functional interactions of aminoacyl-transfer RNA synthetases (tRNA synthetases), an ancient family of catalytic enzymes. tRNA synthetases transport specific amino acids to their tRNAs for the use of ribosomes, the protein-making machinery of the cell, so they can be added to the growing string of amino acids that eventually produce a specific protein.

In a pair of important studies published in the prestigious journals Science and Nature in August and December 2009, respectively, Guo and his colleagues showed the extraordinary lengths that the body goes to make certain that mistakes don't occur during protein building.

In the Science study, for example, the scientists found that the synthetase enzyme not only loads the tRNA with the correct amino acid, but adds one more function to double check it gets attached to the right spot. This editing function is a major mechanism to prevent mistranslation, where the wrong amino acid is inserted at a specific codon. For life to thrive, the challenge of preventing mistranslation through mischarging of tRNA had to be overcome. When the enzyme does make a mistake and it isn't corrected, that error leads to the accumulation of misfolded proteins, which in turn function incorrectly. In animal models, that has led to severe defects, including neurodegeneration.

For that reason, scientists believe that the addition of an editing function occurred prior to the divergence of life into the three kingdoms. The editing function was kept ever since, with strong selective pressure, throughout evolution.

But this addition was just a start. As the tree of life ascended, tRNA synthetases progressively added more functions beyond their original roles, such as being cytokines, or regulating gene transcription. Understanding how the functional switch redirects tRNA synthetases from protein synthesis to transcription regulation is the new focus of Guo at Scripps Florida.

"Cancer cells override the control processes that regulate cell growth and cell division," Guo said. "That ability to regulate gene transcription – the first step in producing a protein – clearly suggests a potential involvement of tRNA synthetases in cancer development." Guo plans to expand his research in this area, focusing on developing potential lead compounds to treat cancers, including melanoma, which accounts for more than 75 percent of all skin cancer deaths. "

One of the most attractive resources of Scripps Florida is the small molecule screening center," he said. "We want to target tRNA synthetases' gene transcriptional functions and develop screens to look for small molecules that can block this function."

Send comments to: mikaono[at]scripps.edu

Assistant Professor Min Guo, formerly a senior postdoc in the Schimmel-Yang lab, officially joins Scripps Florida this month.