Friday, May 3, 2013

Movies & Molecular Biology

I’ve followed the molecular biology of olfaction ever since Linda Buck and Richard Axel burst upon the scene in 1991 with their discovery of the olfactory receptor genes. Along the way I’ve learned some molecular biology—it’s now about as good as my tourist French—and I like to check in on the field at the AChemS conference.

At this year’s meeting was a poster by Françoise Wilkin and colleagues from ChemCom S.A. in Brussels, Belgium, called “Profiling of OR gene expression in the human olfactory epithelium.” While Buck and Axel identified roughly 1,500 mammalian olfactory receptor (OR) genes, it turns out that many of these are non-functional; the exact proportion varies between species. Humans have about 450 functional receptor genes. But that doesn’t necessarily mean that every person actively expresses all 450. Wilkin et al. took olfactory neuroepithelium tissue from eight cadavers and looked for actively expressed receptors. They found 200 of them, or roughly half of the functional OR genome. Of these, 114 were expressed in all eight tissue donors; the rest were expressed in some but not all donors. This variation in expression could account for some of the variability between people in odor perception.

At the Industry Symposium, the theme of which was “Taste And Smell In Translation: Applications From Basic Research,” Joel Mainland from the Monell Chemical Senses Center gave an excellent talk. His topic was “Insights from olfactory receptor screening.” Later, at a reception, we had a chance to talk about why relatively little progress has been made converting olfactory genomics to commercial use (at least when compared to the active work being pursued on taste receptors and novel agonists and antagonists for same). Part of the problem is the sheer number of OR genes one has to deal with. But that can be handled with high throughput screening. What’s really missing is motivation, i.e., specific sensory targets linked to palpable business opportunities. Once the target-plus-application path is clear, the logjam might break.

At the same reception I met Joseph Rucker, Director of R&D at Integral Molecular in Philadelphia. His company develops technologies focused on membrane proteins and thus he is well-informed about OR receptors. (His AChemS talk was “Comprehensive mapping of functional sites for agonists and inhibitors of the bitter taste receptor TAS2R16”). We were talking about ion channels in sensory neurons when Joe reminded me of a 2011 Nature paper by Frank Zufall and others. They investigated loss of function in the SCN9A gene, which encodes a voltage-gated sodium channel. People lacking this gene have a congenital inability to experience pain. Zufall et al. discovered that patients with loss of function mutations in SCN9A are also unable to smell. Mice in which the sodium channel was experimentally deleted from nasal tissue also appeared to be anosmic.

Which brings us to the movies. [About time.—Ed.] [Bite me.] Ronald Niedermann, the giant blond goon in Stieg Larsson’s The Girl Who Played with Fire, and The Girl Who Kicked the Hornets’ Nest, was completely insensitive to pain. This led to some spectacular consequences for Lisbeth Salander, among others. Presumably Niedermann was also anosmic. Since I only watched the movies, this leads to an

Exit question: In Larsson’s novels, was the Ronald Niedermann character anosmic and, if so, how did this affect the plot?

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