Feb 282006
Authors: Lee Newville

Choosing what to eat for lunch hardly seems like an exploration in chemical compounds. But when window shopping for meals, it's easy to forget the role the brain plays in sending the cravings to our tongue that define our appetite and waist size.

The conundrum of what to eat is an almost universal plague for humans, especially as Americans and the rest of the Western world battle nature's time-honored defense against malnourishment – the pure enjoyment of food.

The question of why we crave snacks that harden our hearts and keep our blood sugar elevated relates to the scientific investigation of what researchers call taste transduction, or the transportation of taste stimuli to the brain. CSU has labs that study this phenomenon.

Biomedical Sciences professor Sue Kinnamon studies taste transduction by indulging lab mice in a delectable array of tasty – and sometimes not so tasty – flavored waters in the hope that these critters will reveal the inner workings of how chemical reactions in our tongues and the transportation of these productions to the brain create the sensations of taste.

The unraveling of a mystery and the ensuing controversy

The connotations associated with sweet, sour, salty and bitter tastes have long been familiar to researchers and munchers alike. However, in 1908, Tokyo Imperial University researcher Kikunae Ikeda discovered what he called the fifth taste, dubbed umami (pronounced oo-mom'-ee).

This taste is said to encompass the meaty, savory and broth-like tastes associated with foods like cheese and bacon. Ikeda attributed the enigmatic flavor to glutamic acid crystals (an amino acid), from which he created a food seasoning that wasn't too sour, soluble in water, non-solidifying and unable to absorb humidity.

This seasoning, now commonly known as monosodium glutamate (MSG), was created in 1909 and arrived in the United States in 1917. In the West, the role of this mysterious taste is still controversial.

Some people report intolerance to MSG when used as an additive in foods. Others refute the existence of MSG at all. The most respected scientific debate still looming is the question of whether umami is an actual fifth taste or simply a taste enhancer. Whatever the results, the phenomenon of the movement of taste stimuli for umami chemicals to the brain is not well known.

The same problem is apparent for bitter and sweet taste cells, which lack known taste receptor proteins and are therefore difficult to study. Kinnamon's lab works on this type of research.

How she does it

Kinnamon has been at CSU for 20 years after finishing her doctorate at Kansas State University and post-doctorate research at the University of Colorado Health Sciences Center. She became interested in taste cells early on in her career and dedicated so much work to the topic that she was awarded the Outstanding Achievement Award from the Association for Chemoreception Sciences in 2001.

Her lab experimented with different animals before choosing mice for modeling taste transduction. Originally, she and her colleagues worked with mudpuppies, which are useful because their cells are much larger compared to other animals and are easy to observe.

"The reason we have gone to mice is they are more similar to humans in terms of their taste preferences. The mudpuppies ran out of usefulness when we discovered they only taste bitter and sour," Kinnamon said. "Because they don't have a sweet tooth we couldn't do much more with them."

Kinnamon performs various chemical and behavioral studies to unravel how tastes are transduced from the tongue to the brain. Like many of her colleagues who use animals as models for human systems, Kinnamon purchases mice with genes "knocked out," which means that a certain gene or set of genes has been made inoperative through various genetic techniques.

When Kinnamon hypothesizes that a certain gene is essential for taste sensing, she can use a knockout mouse to test whether that mouse can still sense the taste she is looking at.

Kinnamon then offers a knockout mouse two bottles, one filled with a taste chemical and the other filled with water. Initially, the bottle filled with the taste substance is set below the detection threshold, and the mouse should be drinking equal amounts out of both bottles.

The concentration is then increased and, depending on the taste substance in the bottle, the mouse will either drink more or less of it compared to the pure water.

"As it turns out, if the substance is bitter they'll drink more water and they'll drink more and more water as you increase the concentration of the bitter – if they can taste it," Kinnamon said. "If they're knocked out for a gene that allows them to taste it they'll continue taking the water equally."

Another technique Kinnamon uses is looking at the cells under a microscope. With this technique, Kinnamon uses transgenic mice, or mice that have been infused with the genes of another animal. Green fluorescent protein (GFP), the protein that allows jellyfish to glow under a black light, is placed into the mice to help researchers identify cells.

When Kinnamon wants to look at where the taste cells she wants are congregating, she looks at a thin film of skin on top of the tongue under a microscope with the special light that excites the GFP.

"We used to think we could stick the whole tongue underneath a fluorescent inspection scope," Kinnamon said. "But we haven't had much luck with that."

While Kinnamon and her colleagues are far from the day when the tongue will confuse a piece of kale from a bag of Cheetos, her work could be used to help medicines taste better.

In fact, Kinnamon works on the Scientific Advisory Board for Linguagin, a company that works on the development of compounds that will improve the taste of pharmaceutical, food, and beverage products.

"I'm always interested in how things work in humans and if there's any therapeutic use to be derived it's important to study," said graduate student Lucinda Baker who has worked with Kinnamon for three years. "If we could figure out a way to make drugs that are very bitter more palatable, people might be more compliant in taking them."

Lee Newville can be reached at campus@collegian.com.

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