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Posted: July 22, 2009

The enigma of signaling in olfaction

(Nanowerk News) 'Science is nothing but perception', Plato.
Olfaction (the act of smelling) is a truly enigmatic sense: scientists still do not understand what it is about a particular molecule that smells! We can smell almost any molecule that is small, volatile and hydrophobic enough to get into our smell receptors, but we have no idea how to expect what it does at particular receptor sites and consequently what it will smell like. Predictions for odorants (smell molecules) are not just often wrong, but extravagantly wrong. This is in direct contrast to the level of scientific explanation that exists for the other senses. In hearing, for example, we can accurately determine the pitch and loudness of a sound by analyzing the wave which propagates it. In contrast, nothing physically or chemically obvious about an odorant allows us to predict its action accurately. As we rely so heavily on the perception of the world by our senses it is an odd state of affairs that one of our most basic scientific tools used to investigate the world around us is still so poorly understood.
It is in this context that Dr Jenny Brookes has been awarded a Sir Henry Wellcome Postdoctoral Fellowship from the Wellcome Trust. She will work to understand the mystery of olfaction at the London Centre for Nanotechnology. The London Centre for Nanotechnology is at the forefront of research on nanotechnology and has developed competences and multidisciplinary teams that will enable Dr Jenny Brookes to be successful.
'What I cannot create, I do not understand', Richard Feynman.
The intention of Dr Brookes is to discover exactly what the important initiating interactions are between a small molecule (10's of atoms) such as an odorant and a large protein (10,000's of atoms) such as an olfactory receptor. To this end a group of various experts at Massachusetts Institute of Technology are in the process of creating a 'RealNose' bio-sensor based on real functioning human olfactory receptors. Working with this team of experimentalists in collaboration and matching their state of the art experimental methods with the computational facilities provided here at the London Centre for Nanotechnology (LCN) scientist at the LCN will be able to model accurately and predictively once and for all the methods of odorant signalling employed in the nose. The creation of this 'RealNose' - a nose outside the nose, will finally help expose all the remaining secrets of scent.
There is also a bigger picture that surrounds the context of this work. Smell is, by far, not the only important biological process which remains mysterious. Neurotransmitters, pheremones, steroids and anaesthetics are just a few examples of other small molecules that cause an important cascade of events integral to healthy living. But what is the crucial information that these particular molecules contain in order to define such important and designated roles in biology? How do these molecules convey their important messages to the relevant receptors? Answering such questions could have meteoric implications for modern medicine: if the activity of odorants can be accurately predicted for in vivo from in silico, there may also be profound ramifications for the activity of drugs, as an important example, and therefore better, more rational drug design.
About the London Centre for Nanotechnology
The London Centre for Nanotechnology, is a UK-based, multidisciplinary research centre forming the bridge between the physical and biomedical sciences. It was conceived from the outset with a management structure allowing for a clear focus on scientific excellence, exploitation and commercialisation. It brings together two world leaders in nanotechnology, namely University College London and Imperial College London, in a unique operating model that accesses the combined skills of multiple departments, including medicine, chemistry, physics, electrical and electronic engineering, biochemical engineering, materials and earth sciences, and two leading technology transfer offices.
Source: London Centre for Nanotechnology

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