If we really want to know how our body's cells work or do not work, in the case of disease we might need to look beyond their genes and even beyond the proteins, they are made of. We may need to start going through the cellular "trash."

The group of Dr. Yifat Merbl of the Weizmann Institute of Science developed a system to do just that, finding that "cellular dumpster-diving" contains information about the cell's function that is not otherwise seen.

The group applied their new approach to profiling the immune cells of patients with an autoimmune disorder and discovered distinct evidence for a signature pattern that offers new thinking about the underlying causes of this disease and in the future, may lead to better diagnostic techniques.

Some 70% of the proteins in the body are broken down by the cell's degradation and recycling units known as proteasomes. Included in these are the short-lived proteins that are made for specific purposes, for example, to mount an immune response.

"These proteins may be produced in small amounts, relative to structural proteins, and may be tightly regulated and degraded quickly, so standard proteomics surveys tend to miss them," said Merbl, who is in the Institute's Immunology Department. "But they are precisely the proteins that are crucial to the cell's functions, and thus their malfunctioning plays a role in many diseases."

Preserving proteins in the process of degradation

Crucial to the study's success was the technique the team developed for isolating the proteasomes from cells pulling them out together with the pieces of proteins, or peptides, preserved in the midst of the degradation process inside or around the proteasome machinery.

The team removed the proteasomes from white blood cells taken from both lupus patients and healthy controls, and then carefully pried the peptides out. These were screened with mass spectrometry, and the discarded peptide profile of the two groups compared. The team named their approach MAPP, for Mass spectrometry Analysis of Proteolytic Peptides.

"One of the key advantages of this system is that it allows us to extract information about aberrant processes in cells even from the very low amount of biological material, making the process possibly clinically relevant," says Hila Wolf-Levy, a first co-author of this study, which was published online today inNature Biotechnology.

The lupus group did, indeed, reveal a distinct MAPP profile, clearly separating them from the group of healthy subjects. What's more, the standard proteomics tests the team conducted in comparison did not reveal this division, suggesting that rummaging through the cells' trash may be the key to gaining new insight on this disease on the molecular level.