The Indian connection

Print edition : November 05, 2004

THERE is an Indian connection, though a bit removed, to the Nobel award winning work of deciphering the olfactory system. The study of how we perceive smell remained somewhat neglected in the early part of the last century. A paradigm shift in its approach occurred in the 1970s, with Seymour Benzer's group at Caltech using mutants to pinpoint genes involved in basic mechanisms of sensory perception.

Influenced by this approach, Obaid Siddiqi, who can be called the father of modern biology in the country, pioneered a project in the mid-1970s at the Tata Institute of Fundamental Research (TIFR) to identify single gene mutants that affect olfactory behaviour. The animal model that Siddiqi used was that of the fruitfly (Drosophila melanogaster). Similar work was being attempted in Japan as well.

In principle, this would affect the odorant receptor (O.R.) genes as well as genes that affect the brain's processing of olfactory stimuli. Analysis of mutant behaviour showed that none of them affected O.R. genes per se, but affected the brain. Following Axel and Buck's work we now know that this is not surprising because each O.R. responds to multiple odours.

Therefore, mutation in a single O.R. gene does not affect olfactory responses as other O.R. genes would compensate for this. But Siddiqi's group was the first to design and standardise methods for behavioural assays, measurements of electrical signals from olfactory neurons and measurement of brain responses to odours by functional imaging in the fruitfly.

According to Veronica Rodrigues of the TIFR, a student of Siddiqi who isolated a large number of mutant animals with defective olfactory responses, the tests that Siddiqi designed were simple and research groups currently active in the field, learnt a lot from his work initially.

The importance of the Axel-Buck work, she points out, is that the duo approached the problem head-on. They were aided in this by emerging molecular techniques like PCR (Polymerase Chain Reaction), gene sequencing and so on, which perhaps were not easily accessible in the Indian context then. It was, of course, lot of hard work to fish out the O.R. genes directly. "Axel and Buck followed simple yet elegant logic," says Rodrigues. "They made a few assumptions that the proteins are likely to be G-Protein Coupled Receptors (GPCRs).

The rest was just hard work. While I think this demonstration was valuable, the importance really is in the renewed interest in this area of research, particularly the work of Peter Mombaerts and others that shows how the receptor molecules themselves may be aiding the development of the olfactory circuit."

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