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 the
Advances in
Food Allergy 2012
” series, further details of which can be found here.