Paul Schimmel, Ph.D.
Scripps Research Institute
California
Translating and decoding genetic information to stop disease
Can cancer be cured by delving deeper into the subjects of biology and molecular biology? Quite possibly.
By examining life at its most minute levels, basic research scientists are decoding the structure and function of the building blocks of life, such as DNA, RNA, and proteins. Armed with this fundamental knowledge, scientists hope to correct errors how cells form and function-and intervene in diseases, including cancer.
NFCR Fellow Expertise
Dr. Schimmel, a member of the prestigious Academy of Science, is a leading expert on molecular biology, biochemistry and enzymology. A biochemist and molecular biologist at The Scripps Research Institute in San Diego, Dr. Schimmel has dedicated his 30+-year career to examining the minute forms and intricate functions of molecular biology in an effort to better understand how life works. He focuses on decoding genetic information in translation, protein-RNA recognition, and the connections between translation and cell signaling.
Dr. Schimmel is one of the few scientists to study both nucleic acids and proteins, and his laboratory was one of the first to identify the operational RNA code for amino acids, which possibly was the original code of life.
NFCR Research Overview
With financial assistance from the National Foundation for Cancer Research, Dr. Schimmel is investigating the components in cells that are responsible for protein synthesis and the genetic code. By understanding how these components interact with one another, Dr. Schimmel hopes to learn how they might be used to turn off a variety of disease processes, including infectious microorganisms, viruses, and cancers. Specifically, he is focusing on how peptides and proteins are synthesized in a cell, a task which is accomplished by a molecular mechanism called the translation apparatus.
NFCR Research Findings
Dr. Schimmel and his team recently have discovered that a component of the protein synthesis apparatus in human cells also seems to play a role in cellular events related to programmed cell death, inflammation, and potentially, cancer. By literally taking apart the RNA molecule, he proved that it contained a distinct but related code that selected the building blocks. This operational RNA code communicates the specific sequences of RNA to specific amino acids that are necessary to synthesize proteins. His further work uncovered even more detailed information about the atoms that make up the operational RNA. Additionally, Dr. Schimmel demonstrated how the RNA structure works to make the genetic code more accurate.
Future Research Goals
Dr. Schimmel hopes to use his recent findings to correct cellular malfunctions. He has shown that small molecules can bind selectively to specific RNA targets. This insight can be used to turn off a variety of disease processes, particularly cancer. For example, p53 is one of the major genes that suppress tumors. But a defect in the p53 gene turns off that tumor blocking capability, resulting in the development of many kinds of cancer. Dr. Schimmel is working to show that some of these mutations can be corrected by adding one small molecule that binds to a specific RNA structure, which in turn prevents the defect. Dr. Schimmel also is exploring the development of drugs that are directed at defective RNA and protein targets. He has developed the technology to direct small molecules to bind selectively to targets that could, in principle, correct defects and turn off disease processes.
Impact on Cancer Prevention, Treatment, or Cure
Dr. Schimmel's detailed understanding of how RNA directs protein synthesis provides dramatic clues about the origin of life. Just as important, his work has shed light on how genetic mistakes occur-and how new drugs might be developed that could correct these mistakes. Cellular defects can be corrected by binding drugs to RNA targets. Microorganisms that cause infections or viruses can be eliminated by directing drugs to precise targets. Tumor cells can be eliminated by blocking specific proteins, while sparing healthy cells. Dr. Schimmel's ground-breaking work has the potential to extend and improve life for all of us.