Award details

Odour binding proteins: Transport mechanism or first step in odour coding

Reference	BB/D522870/1
Principal Investigator / Supervisor	Dr David Scott
Co-Investigators / Co-Supervisors	Dr David Cook, Professor Andrew Taylor
Institution	University of Nottingham
Department	Sch of Biosciences
Funding type	Research
Value (£)	250,468
Status	Completed
Type	Research Grant
Start date	01/10/2005
End date	30/04/2009
Duration	43 months

Abstract

We are able to perceive around 2500 different odours, some at the level of 1 part in 10 to the power of 15. This exquisite sensitivity is in a large part to the unique neuronal architecture of the olfactory epithelium. Each cell expresses only one of over a 1000 possible receptors. Each odour is therefore thought to interact differently with each of these receptors causing differential firing of neurons and leading to odour discrimination and perception in the brain. The odours are typically small (less than 500 Da) volatile hydrophobic molecules that are not typically soluble in water or the mucus layer. Therefore there is a problem in the transport of these molecules across this layer to the Odour Receptors (ORs). This transport is thought to be mediated via the Odour Binding Proteins (OBPs) which are c.a.20 kDa proteins of the lipocallin superfamily that have a small hydrophobic pocket capable of sequestering odours. The number of OBPs varies between species: vertebrates typically have 3-4; although porcupines have 7; while insects have in excess of 9-10. Rat OBPs have been shown to be specific for different classes of small molecules, and therefore it would appear that there is a role of the OBP in some form of odour coding over and above that already present by the ORs. Previous studies have been solution based using soluble odours; we wish to supercede these studies by constructing an experimental system that allows real time monitoring of OBP binding in the gas phase. Crude proof of concept studies have shown that it is possible to observe OBP binding by depletion of gas phase components, monitored by on-line mass spectrometry. Further more, we are able to observe competition between odours, and the dynamics of binding. We wish to extend this study to encompass a panolopy of odours, odour competition and OBP type. We will use rat OBP initially due to the availability of a high expressing clone in Pichia and its excellent stability. Once we have characterisedthe strength and dynamics of binding, as well as the competition of binding, we will use the less stable human OBP-2A to produce data on the role of human OBPs in odour coding.

Summary

Smell is one of the most important senses. It tells us whether our food will taste good, and alerts us to things which are bad for us. Despite years of intensive research there are still large gaps in our knowledge as to how exactly we sense smells. Typically we can distinguish between 2500 different odours, some of which are only available in very small amounts. Axel and Buck won the 2004 Nobel Prize in Medicine for discovering that each neuron in the specialised part of the nose called the olfactory epithelium has only one of a 1000 possible receptors. Therefore this leads to the theory that each cell, through having only one odour receptor, interacts differently with an odour and therefore the neurons fire in different combinations giving rise to a different perceptions for different odours. There is one issue still to be resolved, and that is how do small volatite odours, many of whom do not dissolve in water, make it across the mucus layer and to the odour receptors. This role is thought to be carried out by the odour binding protein (OBP). It is unclear as to whether the OBP acts as a shuttle to get the odour across the mucus layer to the receptor, or binds different odours with different strengths and therefore is involved in some way in discrimination of odours. We have constructed a simple set of experiments to test these hypothesis. We will also test odours in competition with each other, and why some odours are sensed almost instanteously, and others can take several seconds to be perceived. There results will have profound importance for how we think about odour perception.

Committee	Closed Committee - Agri-food (AF)
Research Topics	Microbiology, Neuroscience and Behaviour, Technology and Methods Development
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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