Could biophysics help Novak Djokovic?

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Last year, ATP World Tennis Number 1 Novak Djokovic cut out all wheat products from his diet. According to his nutritionist—who “discovered” an intolerance to gluten—It was this drastic change in eating habits that led directly to his current dominance of the game.

Unfortunately, this approach is currently the only effective treatment available for sufferers of the condition, and can feel far from a grand-slam solution to the problem. The widespread use of cereals in the global food industry, especially in the routine use of “hidden” wheat-derived ingredients in processed food, can often make adherence to such restrictive regimes a dispiriting experience.

What if there was an alternative?

In a Correspondence article published today in BMC Biophysics, Stephen Harding and colleagues propose an exciting new way of looking at this issue, through the use of techniques developed in the field of molecular biophysics—and issue a challenge to researchers working in the field to test their idea.

Protein prevention

Gluten intolerance is an autoimmune condition affecting individuals with genetic susceptibility, and occurs as a result of inflammation of the gut in response to exposure to cereal proteins known as gliadins.
Although some previous research has looked into the possibility of genetically modifying these proteins in order to prevent this response, this new approach instead focuses on asking whether it would be possible to add a naturally occurring ingredient into the mix that might block this exposure in the first instance.

The candidate ingredients for this are dietary fibre polysaccharides—complex, indigestible carbohydrates that are nevertheless essential for digestion. When consumed, these fibre molecules compete directly with the cereal proteins for exposure to the bowel tissue, forming larger complexes that might be much less able to illicit the harmful inflammatory response.

Biophysical techniques

One major issue with making this approach a success is identifying suitable polysaccharides that would interact strongly enough with these cereal proteins to prevent inflammation. This is where biophysics can help.

The authors reason that such candidate molecules can be found using a technique known as analytical ultracentrifugation. Senior author Stephen Harding from the University of Nottingham UK explains: “The analytical ultracentrifuge is a high speed centrifuge with an optical system which allows the detection of macromolecules as they sediment under high g-force. It has an inherent separation ability and is highly resolving. It is a free solution technique not requiring immobilisation of macromolecules onto a surface, giving it a major advantage over (other) techniques”

He continued “We use primarily the sedimentation velocity method and use the principle of co-sedimentation: gliadins, particularly digested gliadins have a very small sedimentation coefficient, whereas fibre polysaccharides are generally higher.  From appropriate comparison of mixtures with controls, we can see if the gliadin is picked up by the polysaccharide”

Although the technique itself is not a new one—the Swedish chemist Theodor Svedberg won the Nobel prize for its invention in 1926—modern developments now mean that these interactions can be analysed in exquisite detail.

What next?

Although only a fledgling idea at present, Harding is excited about how future research might tackle this challenge “A complete range of fibre needs to be investigated in a systematic way to see if there are any fibre polysaccharides providing interactions that are strong and robust enough. If this is the case then the particular gliadins and peptide sequences binding to the different polysaccharides would then need to be determined.”

After identification of these molecules, clinical trials could then be considered in patients with the condition. However, despite the potential this might offer for sufferers, the researchers are urging caution at this early stage “We must stress we do not want to give false hope to people who have gluten intolerance problems. This is
very much a first stage process and it is possible that no fibre can be found affording an interaction suitable enough…
If we can do so this it might provide a useful first step in identifying which fibre merits further investigation”

For researchers in the field, it seems the ball is now in their court.

This Correspondence piece will appear as a guest article as part of theAdvances in Food Allergy 2012” series, further details of which can be found here.

 

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Cindy Jensen

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