Conference findings

July 14, 2000

Chemistry of being explored

They look like ludicrous surrealist art, all spirals, blobs and streamers. Yet within the curious and wildly varying structures of proteins lie the workings of life.

At its simplest level, the genome is simply an A to Z of proteins while their study, proteomics, will be one of biology's "next big things".

This means getting to grips with all that structure.

At the University of Basel in Switzerland, Andreas Engel and his colleagues are using a technique called atomic force microscopy (AF) to take a closer look.

The method is ideally suited to this task.

It works by running a stylus a tenth of a millimetre long and a mere millionth of a metre thick over the surface of a sample.

The slightest deflection of the stylus by the intermolecular forces with the surface it is investigating can be detected to give an astonishing resolution of one angstrom in the vertical scale and ten angstroms in the horizontal.

It can be used to look at living cells and pick apart the chemistry of life in exquisite detail - perfect for studying proteins.

"There's nothing else available to enable you to look at life molecules with this resolution," said Dr Engel.

He is using AF, combined with X-ray crystallography, to reveal the three-dimensional structure of membrane proteins involved in water transport in cells.

When this important process goes wrong, the consequences for a person's health can be severe.

Understanding what these proteins look like will help explain how they work and possibly suggest therapies that might correct the fault.

No easy fix for obesity It seems there is no easy way to lose weight. Experiments to explore the prospect of a genetic and biochemical short-cut to combat obesity involving the small-protein hormone leptin and its gene are revealing just how complex weight regulation really is.

Jeffrey Friedman, who discovered leptin and the ob gene that creates it at Rockefeller University, New York, has been studying the neural response to the chemical while searching for other genes that play a role.

His initial work appeared to show that leptin may well be the key to losing weight and could lead to the creation of effective medications to tackle obesity.

Mice with faulty copies of the ob gene, and which could not produce leptin, ate without restraint, becoming obese. Conversely, when given doses of the hormone, they lost weight.

It did not seem simply to affect appetite, as the leptin doses led to a reduction in fat, whereas dieting also produces a drop in muscle.

However, subsequent research has shown that the overwhelming majority of obese people actually have above-average levels of the chemical in their bodies - it seems that they are intrinsically insensitive to its effects.

This suggests that only a minority, perhaps as few as one in ten, who had normal or low levels of leptin, might benefit from a drug based on the hormone.

"Chemical studies indicate leptin is not a magic bullet, but there is at least reason to believe a sub-set of individuals might respond," said Dr Friedman.

Work is now focusing on how the hormone acts on part of the brain called the hypothalamus, to give it an indication of how much fat is being stored in the body.

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