Now, after years of painstaking research, scientists have succeeded in duplicating the disease's most critical features in the most readily manipulated model organism in existence. In research published in this week's issue of the journal Science, a team from Whitehead Institute for Biomedical Research used common baker's yeast as a living test tube to show how just a small amount of a Parkinson's-related neuronal protein called alpha-synuclein (aSyn) can convince neighboring proteins to abandon their normal shape and form these deadly clusters.

"For the first time we can initiate the process synchronously in living cells and watch what is happening in real time," says Susan Lindquist, director of Whitehead Institute and a lead author of this new study.

A protein's shape is critical to its function: When a protein changes its shape, it changes function, and this can be deadly. Many neurodegenerative diseases such as Parkinson's are thought to be caused by proteins like aSyn that can misfold into abnormal shapes and lose their ability to function correctly or even wreak havoc in the cell.

So say two University of Florida scientists who have used the newly developed techniques of 'paleobiochemistry' to reconstruct ancient bacterial proteins based on similarities in the genetic sequences of modern proteins. The resurrected proteins proved most stable and functional at temperatures between 130 and 150 degrees Fahrenheit, implying that ancient bacteria lived in a hot springs-like soup warmer than most life can tolerate today.

For proteins, form really does equal function. Not only are they essential building blocks of the body, but proteins are also the workers of every cell, carrying out its specific functions. This function depends on the ultimate three-dimensional shape of the protein, a form achieved by folding flexible chains of amino acids until each is properly aligned so that the protein can do its job. Normally, the folding of proteins is highly efficient and specific, but sometimes the process goes awry, resulting in dangerous misfolded forms.

The technique, which Hecht developed over the last 10 years and validated in experiments to be published in November, could prove useful in a wide range of fields. Custom-designed proteins, for example, could become a source of new drugs or could form the basis of new materials that mimic the strength and resilience of natural substances.

The range of proteins present in nature, while great, has evolved only as far as the needs of biological organisms, said Hecht. "Why should we be limited by a mere few million proteins?" he said. "We can now not only ask what already exists in the biological world, but go beyond that and ask what might be possible."

Everett Lipman, a new assistant professor of physics at the University of California, Santa Barbara, recently co-authored an article in the journal Science, describing an innovative study of how to "see" proteins as they fold, the result of experiments performed with co-workers at the National Institutes of Health.

The machinery of life arises from interactions between protein molecules, whose functions depend on the three-dimensional shapes into which they fold, said Lipman. Although proteins are composed of just 20 different building blocks (the amino acids), the process by which a given sequence of these components adopts its unique structure is complex and poorly understood. Folding proteins are too small to view with a microscope, so the researchers used a method called Forster Resonance Energy Transfer, or FRET, to study them. Using a microfabricated silicon device and a microfluidic mixing technique, they were able to observe single protein molecules at various times after folding was triggered.

According to the researchers, their findings point the way to studies that could begin to clarify the factors that determine whether a prion specific to cattle that causes bovine spongiform encephalopathy (BSE), or mad cow disease, might become infectious to humans.

The studies also suggest a new approach for treating disorders such as Alzheimer's disease that involve aberrant protein folding, said the researchers. It might be possible to develop drugs that would influence toxic proteins that aggregate into brain-clogging plaque to fold into less toxic versions, they said.

The work, presented in the Aug. 29 edition of Science, marks the first time protein-folding kinetics has been monitored on the single-molecule level. Proteins are long chains of amino acids. Like shoelaces, they loop about each other or fold in a variety of ways, and only one way allows the protein to function properly. Just as a knotted shoelace can be a problem, a misfolded protein can do serious damage. Many diseases, such as Alzheimer's, cystic fibrosis, mad cow disease and many cancers result from misfolded protein.

“We believe this is a new force in nature,” said Ariel Fernández, a Visiting Scholar in the Institute for Biophysical Dynamics. “It’s never been properly characterized before and it seems to be at the core of biological phenomena when examined at the nanoscale.”

"We believe this is a new force in nature," said Ariel Fernandez, a Visiting Scholar at the University of Chicago's Institute for Biophysical Dynamics. "It's never been properly characterized before and it seems to be at the core of biological phenomena when examined at the nanoscale."

Fernandez and Ridgway Scott, Professor in Computer Science and Mathematics at the University of Chicago, will announce the discovery in the July 4 issue of Physical Review Letters. The study combines proteomics-the computational approach to the study of proteins-with physical chemistry, which delves into the effect of chemical structure on physical properties.