In a series of experiments, the scientists found that when yeast's protein-building machinery recognizes the starting line for a gene's instructions, it first alters its structure and then releases a factor known as eIF1, a step necessary to let it continue reading the assembly instructions. Even though yeast are the most primitive relatives of humans, the protein-building machinery, or ribosomes, of each are quite similar.

"The idea is to really know at the molecular level how life is put together," says Jon Lorsch, Ph.D., professor of biophysics and biophysical chemistry, one of the departments in Johns Hopkins' Institute for Basic Biomedical Sciences. "We see disease largely as an incorrect timing event -- the wrong thing happening at the wrong time, or the lack of the right thing."

As a result, Lorsch studies the timing of how the ribosome complex itself assembles and how other factors come and go as it translates genetic information to build proteins, the workhorses of cells. If the ribosome doesn't start in the right place along a gene's instructions, it will make the wrong protein, which can kill the cell or lead to disease.

"The ribosome is the end stage of gene expression, and gene expression keeps us alive and causes disease," says Lorsch. "If we can better understand how the ribosome works, perhaps we can harness it to help us fix disease."

Already, scientists knew that without eIF1, the ribosome can start reading the gene's RNA instructions at places other than a particular three-block piece of RNA known as the "start codon." And excessive amounts of eIF1 are associated with cardiac hypertrophy, or an enlarged heart.

While eIF1's role in cardiac hypertrophy remains a mystery, the new
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
21-Jan-2005