Trends4Tomorrow (February 26, 2009) — Smell is one of the most complex and least-understood senses. Humans have a vast olfactory system that includes close to involving a huge array of proteins that detect odors, known as “olfactory receptors.” These are specified by over 400 functional genes; that’s more than the number dedicated to any other bodily function. And some animals, such as dogs and mice, have around 1,000 functional genes specifying “olfactory receptors.”

That variety of receptors allows humans and animals to discern tens of thousands of distinct odors. Each odor activates multiple receptors and this pattern of activation creates a signature that the brain can recognize as a particular scent.

MIT biological engineers have found a way to mass-produce these smell receptors in the laboratory, an advance that paves the way for "artificial noses" to be created and used in a variety of settings.  Soon, this research could unlock the mystery of how the sense of smell recognizes a seemingly infinite range of odors.

Shuguang Zhang, associate director of MIT's Center for Biomedical Engineering, and his team recently published described this discovery in the Proceedings of the National Academy of Sciences (PNAS).  Zhang and his colleagues, also recently received funding from DARPA for the team's “RealNose project.”

Until now, efforts to understand the molecular basis of smell have been stymied by the difficulty in working with the proteins that detect odors, known as “olfactory receptors.”
But with the new methods, olfactory receptors are finally available as a raw material for researchers to utilize in smell research.

The olfactory receptors that bind to odor molecules are membrane proteins, which span the cell surface. Since cell membranes are composed of a bi-layer of fatty lipid molecules, the receptor proteins are highly hydrophobic (i. e., water-fearing).

When such proteins are removed from the cell and placed in water-based solutions, they clump up and lose their structure. That makes it very difficult to isolate the proteins in quantities large enough to study in detail. The new method makes it possible to isolate and purify the proteins by performing each step in a hydrophobic detergent solution, which allows the proteins to maintain their structure and function.

The technique involves a cell-free synthesis using commercially available wheat germ extract to produce a particular receptor, then isolating the protein through several purification steps. The method can rapidly produce large amounts of protein -- enough to start structural and functional studies.

In future work, the team plans to work with researchers worldwide to develop a portable micro-fluidic device that can identify an array of different odors. Such a device could be used in medicine for the early diagnosis of certain diseases that produce distinctive odors, such as diabetes and lung, bladder and skin cancers. There is also a wide range of industrial applications for such a smell-based bio-sensing device.