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Genomes: A Platform for Signal Transduction Research?

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Is the Genome Approach Really Better?

26 March 2001

Md. Shahidul Islam

There is no doubt that "information" obtained from genome sequencing projects will be helpful to identify new proteins associated with a variety of signalling pathways. However, I can see disadvantages of approaching questions associated with signalling on a genomic scale.

One should remember that discovery of several major signalling molecules and systems that can be considered as true breakthrough occured during pregenomic years. Discoveries of cAMP, NO, and IP3 are some of these examples. It is not obvious how knowledge of genomics will directly contribute to discovery of, as yet unknown, small diffusible second messengers that are comparable to cAMP or NO but that still belong to, as yet, unidentified signalling pathways. True novelty in Biology is rare and it is likely that breakthroughs in signalling will require a lot of thinking and intuitive works, much in the line of classical approaches used in the past and not just by looking at the sequences and peptides.

Another major concern in the post genomic era is that there is a tendency to think and act on "genomic scale" even when it comes to signalling research. Thus, you will come across colourful data obtained from DNA arrays which are simply too much or too difficult to understand. Investigators are choosing to work with a lot of molecules (often thousands) at a time rather than concentrating on one molecule and build up a vertical growth of knowledge on that molecule. It looks like that working with large number of molecules all at a time is thought to be more fashionable in the post-genomic age as opposed to working with one molecule at a time. I have been working on one single molecule (whose function is known) since last ten years and about 2000 other investigators have spent about 20 years of research on this single molecule. Still it seems we know very little about it even today. I can not imagine how satisfying it will be to a classical scientist to try to know superficially a large number of molecules (genomic scale) rather than focussing on molecules one at a time.

Identification of molecules and hopefully their function are one thing, but life is simply not additions of molecules. Understanding functions would require understanding properties of complex signalling networks and their emergent properties. This is a tremendous task that will keep busy a huge number of scientists over rest of their lifetime. There is, thus, no straight forward way to advance the field of signal transduction at a faster rate by merely by analysing large number of genes all at one time. To some extent, this situation is creating a kind of restlessness in the minds of conventional scientists and also diverting resources from conventional research to genomic research. My belief is that science will benefit more if we do follow rather conventional research approaches with emphasis on human intelligence and intuition as well as hard work, rather than on thinking and acting on "genomic scale".

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