The breakthrough may pave the way to drugs that fight illnesses such as Alzheimer's, Parkinson's disease, diabetes and a host of viral infections, the scientists said.

"That's why there's so much interest in this paper," said lead researcher Junying Yuan, a professor of cell biology at Harvard University Medical School.

Her team's findings are published in the Feb. 11 issue of Science.

Almost every illness involves the death of an excessive number of body cells due to stresses from both inside and outside the cell. Biologists call one of the most potent forms of cellular stress "endoplasmic reticulum (ER) stress."

“This is a unique signaling pathway,� says Randal Kaufman, Ph.D., a professor of biological chemistry in the U-M Medical School and an HHMI investigator. “In most pathways, there are multiple components and crosstalk. But there’s only one IRE1 gene and one protein that carries out a unique biochemical reaction. This makes IRE1 a perfect target for pharmacological intervention for B cell-driven autoimmune diseases, like myasthenia gravis or systemic lupus erythematosus.�

Results from the study will be published in the Feb. 1 issue of the Journal of Clinical Investigation.

Kaufman studies fundamental signaling pathways involved in the production of new proteins in the cell’s endoplasmic reticulum (ER). The process begins with chains of amino acids, which are deposited in the ER membrane in response to coded instructions from genes. Chaperone proteins fold these amino acid chains into specific shapes and direct them to different areas of the ER for processing.

That's why the Human Proteome Folding Project -- a recent collaboration between IBM, United Devices, the Institute for Systems Biology and the University of Washington -- is picking up where the Human Genome Project left off. Understanding the form and function of these proteins, which are at the core of many diseases and the natural target for many treatment drugs, will ultimately put researchers that much closer to understanding why certain diseases happen and how to treat and cure them.

"The Human Genome Project is the foundation on which this project sits," say Dr. Rich Bonneau, senior scientist for the Institute for Systems Biology, the Seattle, Washington non-profit research institute that is spearheading the biology research effort for the Human Proteome Folding Project.

The scene is all too familiar. A parent opens the door to a messy room with clothes strewn about and yells at the sulking teen, "Clean up your room ... and fold up those clothes!" Understandably, the teen is not very motivated by such a mundane task.

In fact, we rarely give folding more than a second thought. At the microscopic level, though, folding takes on a whole new meaning. A team of A&M scientists, led by biochemistry professors James Sacchettini and Ry Young, report on a protein that can transform from a molecular bystander to a chemical bulldozer by changing the way it is folded. Their results were published in the Jan. 7 issue of the journal Science.

Our bodies are made up of different types of cells, which are themselves made up of different types of molecules. Some of the molecules, called proteins, are linear chains of different chemical blocks called amino acids and the true workhorses of the biochemical world.

A snake-like chain of amino acids without a distinct shape is virtually useless. Therefore, a protein must fold into a varying three-dimensional shape to function properly. This holds true in all life forms, from complex humans to bacteria made of only one tiny cell.

Nick Pace, professor of biochemistry at A&M, studies protein folding. He is one of many scientists trying to solve the "protein folding problem."

"Protein folding means being able to predict the three-dimensional structure of a protein," Pace said.

In research published recently in the online version of the scientific journal Nature Biotechnology, Los Alamos scientists Stéphanie Cabantous, Tom Terwilliger and Geoff Waldo describe a method for engineering soluble, self-associating fragments of green fluorescent proteins that can be used to tag or detect soluble and insoluble proteins in living cells or cell lysates without changing protein solubility.

We all know that it is essential for life. However, probably because of its abundance and simple chemical composition, we often regard this tasteless and odorless substance as being important, but quite simple and ordinary. Scientifically, it is the exact opposite. It appears to show extremely complex and unusual behavior. It is the most studied substance on Earth. Yet, scientists are still puzzled over its strange properties. Even the best computers we have today cannot simulate all of the different properties of water.

Let us look at an example of the surprising properties of water. The strangeness of water starts with the fact that it exists on Earth. Water, being composed of two fairly light atoms (hydrogen and oxygen), should be in the gas phase at the usual temperature ranges that exist in our world. In fact, all compounds that are close to it (i.e. H2S, H2Se, and H2Te) are found mostly in the gas phase. But, compared to similar substances, it melts about 100 degrees above the expected melting point and it boils about 150 degrees above the expected boiling point (see Figure 1). The result is that it is the only material that exists naturally in all three forms (i.e. as ice, liquid, and vapor) on Earth.

In addition to the example given in the previous paragraph, water has at least 40 different surprising properties (See for example the “Forty-one anomalies of water� section in Ref 1). But, what is even more astonishing is the fact that most of these anomalous properties of water are absolutely crucial for life. Simply stated, life on Earth depends on these extraordinary aspects of water. Below we will discuss some of the anomalous properties of water and their importance for life. At the end we will briefly try to explain why water behaves so differently.

Part of a cellular mechanism that regulates the folding of new proteins into their proper shapes also includes a genetic response that enlarges the factory where both protein folding and packaging of proteins occurs. This finding, from researchers at St. Jude Children's Research Hospital, Loyola University (Chicago) and Kyoto University (Kyoto, Japan), are published in the Oct. 15 issue of the Journal of Cell Biology.

The link between protein folding and factory construction ensures that the two processes are coordinated when the cell is called upon to quickly make, fold and secrete large amounts of specific proteins.

The investigators discovered that the cell makes a molecule called XBP1 in response to an increased demand on the protein-folding machinery. This increased demand for folded proteins triggers the so-called unfolded protein response (UPR), as well as the expansion of the factory where proteins are folded and packaged so they can be secreted from the cell. The UPR also prompts the cell to make molecules called chaperones, which do the actual task of protein folding.

XBP1 triggers the cell to make phosphatidylcholine, the major building block of the rows of membranes that make up much of the factory, which is called the endoplasmic reticulum (ER). Membranes in the ER serve as envelopes to package the folded proteins.

The disease, called GM1 gangliosidosis, disrupts the normal function of brain cells and causes them to self-destruct. The St. Jude discovery offers strong evidence for the cause of GM1 gangliosidosis in children. GM1 gangliosidosis is a lysosomal storage disorders, an inherited disease in which one or more enzymes in the lysosomes are defective. Lysosomes are the cell's recycling centers, where proteins, fats and other molecules are broken down into their basic building blocks, which are then reused to make new molecules.

Lysosomal storage diseases occur when lysosomes lack the enzymes they need to perform their recycling tasks, leading to abnormal accumulation of the molecules the lysosome is supposed to break down. These diseases are responsible for most severe cases of nerve degeneration and mental retardation among children.

A new method to probe the forces that control higher order structure in proteins under native conditions—that is, structure-promoting conditions for the protein—has been developed by chemists at the University of Wisconsin, Madison.

The structure of the chaperonin complex of the bacteria Thermus thermophilus reveals clues about how the important molecule may do its job of folding new or damaged proteins within cells. Led by Professor So Iwata of Imperial College London, the team of scientists announce their findings in this month’s edition of the journal Structure (August 2004).