Published September 19, 2013
Thanks to efforts like the Human Genome Project, scientists are unraveling the role that genes play in the development of such diseases as cancer and Alzheimer’s.
But knowledge of proteins, another essential molecule linked to many of the same ailments, is less advanced.
That is changing due in part to UB researcher Sheldon Park, who received a $300,000 National Science Foundation grant to develop technology that dramatically reduces the time it takes to characterize proteins.
“We are creating a method that allows researchers to eliminate protein function in just a few days so that its role in the cell can be examined. Previously, this type of work might have taken months,” says Park, assistant professor of chemical and biological engineering.
The breakthrough technology could be useful in proteomics, a field of study akin to genomics. In what many see as the next step after the completion of the Human Genome Project, proteomics aims to characterize the estimated million or so unique proteins in the human body.
Until recently, however, that didn’t seem possible.
The human body consists of roughly 21,000 genes, each of which can spawn proteins of different size and function. As a result, it has been difficult to characterize what proteins do, despite efforts of pharmaceutical companies, government agencies and research institutes.
Researchers often study proteins by creating temperature-sensitive mutant proteins. These mutants work like the original proteins at low temperatures but stop working at higher temperatures. By comparing the growth and metabolism of cells at different temperatures, scientists can determine the mutated protein’s function.
The problem: creating temperature-sensitive mutants is not easy and often impossible. Typically, researchers must screen a few thousand mutants before identifying a useful one. This painstaking process can take months and it needs to be repeated for each protein studied.
“It’s a very laborious process. It’s very time consuming and, unfortunately, not very predictable,” Park says.
To simplify the matter, he is designing a module that, when fused to a protein, converts the protein into a temperature-sensitive mutant. A key element of the design is an enzyme called intein, which can be used to shuttle the protein to different areas of the cell by changes in temperature. As the protein moves from one area of the cell to another, scientists are able to infer its function by examining what happens in the cell.
The technology has the potential to be used widely in chemical research, biotechnology, medicine and other fields.
“The grant will allow us to develop a method that uses an engineered intein to synthesize useful drug candidates,” Park says. “In turn, this will give researchers the ability to gather information about proteins in a much more timely manner and help accelerate the rate of discovery. This is welcoming news as we enter the brave new world of protein molecules.”