Two recent high profile publications, in Nature and the Proceedings of the National Academy of Sciences, reveal yet another fascinating facet of olfaction.
Many of us who own pets will know that animals appear to have a canny ability to know when we are sick. Stories abound about dogs or cats that can smell cancerous tumors or other illnesses (I seem to remember Gregory House (above) citing this phenomenon when faced with the logical alternative, a feline harbinger of death!) Wild animals will often avoid sick members of their own species, a strategy that has obvious evolutionary advantages in the face of infectious agents or predators seeking an easy meal.
But how does this work? You might suppose that animals are responding to a behavioral change in the sick individual. You feel sick, therefore you behave differently, therefore your pet pooch behaves differently. But what if the animal could actually smell sickness? And if it could, how does it know what sickness smells like? Two research groups have now provided a potential molecular mechanism for how animals could detect infections using their sense of smell.
The labs of Ivan Rodriguez and, independently, Linda Buck identified a new class of olfactory receptor in the laboratory mouse. This is the fifth class of receptor known to be involved in mediating olfaction, but what sets it apart from the others is the unique nature of its ligands (the molecules the receptors bind). The ligands are formylated peptides: small proteins that have an aldehyde group attached to the first amino acid.
So far so interesting, but how does detecting these peptides indicate sickness? Well formylated peptides are relatively rare in nature, but they are produced by bacteria which, of course, are often a source of pathogenic illness. Therefore, in theory at least, mice should be able to smell the presence of specific types bacteria using these receptors.
Intriguingly the receptors are found in the part of the nose that detects pheromones - which are chemical signals that are exchanged between animals or social purposes. This suggests that the new receptors are involved in regulating a fundamental behavior, rather than simply detecting an odor, and implies that detection would result in some kind of instinctive behavioral response (i.e. avoidance).
But I am getting ahead of myself slightly, because these publications simply describe the receptors and show that they can detect peptides when presented in a purified manner. It remains to be seen if the mice detect bacterial peptides from other mice in a more natural context, and whether this results in a stereotyped behavioral response. Its also unclear the extent to which the same system is functional in other mammals; it does not appear to be present in humans, for example. Nevertheless, I find it remarkable that - even in this post-genomic era - there are still entire sensory sub-systems that we know nothing about.
I was at a meeting recently where Linda Buck (the lead scientist on one of these papers and someone with quite the record in this field: she shared the 2004 Nobel Prize for discovering the first olfactory receptors) was asked if this was the last class of olfactory receptors to be described. She thought it was likely, but either way, these reports show that we have much still to learn about scents and sensibility. I hope, in this blog, to chart some of the more interesting aspects of that journey.
Many of us who own pets will know that animals appear to have a canny ability to know when we are sick. Stories abound about dogs or cats that can smell cancerous tumors or other illnesses (I seem to remember Gregory House (above) citing this phenomenon when faced with the logical alternative, a feline harbinger of death!) Wild animals will often avoid sick members of their own species, a strategy that has obvious evolutionary advantages in the face of infectious agents or predators seeking an easy meal.
But how does this work? You might suppose that animals are responding to a behavioral change in the sick individual. You feel sick, therefore you behave differently, therefore your pet pooch behaves differently. But what if the animal could actually smell sickness? And if it could, how does it know what sickness smells like? Two research groups have now provided a potential molecular mechanism for how animals could detect infections using their sense of smell.
The labs of Ivan Rodriguez and, independently, Linda Buck identified a new class of olfactory receptor in the laboratory mouse. This is the fifth class of receptor known to be involved in mediating olfaction, but what sets it apart from the others is the unique nature of its ligands (the molecules the receptors bind). The ligands are formylated peptides: small proteins that have an aldehyde group attached to the first amino acid.
So far so interesting, but how does detecting these peptides indicate sickness? Well formylated peptides are relatively rare in nature, but they are produced by bacteria which, of course, are often a source of pathogenic illness. Therefore, in theory at least, mice should be able to smell the presence of specific types bacteria using these receptors.
Intriguingly the receptors are found in the part of the nose that detects pheromones - which are chemical signals that are exchanged between animals or social purposes. This suggests that the new receptors are involved in regulating a fundamental behavior, rather than simply detecting an odor, and implies that detection would result in some kind of instinctive behavioral response (i.e. avoidance).
But I am getting ahead of myself slightly, because these publications simply describe the receptors and show that they can detect peptides when presented in a purified manner. It remains to be seen if the mice detect bacterial peptides from other mice in a more natural context, and whether this results in a stereotyped behavioral response. Its also unclear the extent to which the same system is functional in other mammals; it does not appear to be present in humans, for example. Nevertheless, I find it remarkable that - even in this post-genomic era - there are still entire sensory sub-systems that we know nothing about.
I was at a meeting recently where Linda Buck (the lead scientist on one of these papers and someone with quite the record in this field: she shared the 2004 Nobel Prize for discovering the first olfactory receptors) was asked if this was the last class of olfactory receptors to be described. She thought it was likely, but either way, these reports show that we have much still to learn about scents and sensibility. I hope, in this blog, to chart some of the more interesting aspects of that journey.
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