Genomes: A Platform for Signal Transduction Research?


Genomes: A Platform for Signal Transduction Research?

Is the Genome Approach Really Better?

Mar 26 2001 7:11AM

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".

Cell signalling networks

Mar 27 2001 10:29AM

Venky Ramakrishna

Someone once said, "Information is only as good as your ability to make use of it." This was true a decade ago and is true today.

I think public access to any of the databases of the human genome is as important as defining how best to use the information. I also think this is a massive task for any single institution even if there was funding. Basically, I am against empowering any one entity to deal with the information. I am in favor of a Global Consortium or Global Network which further breaks down into individual areas- Cancer, Infectious Disease, Autoimmune Diseases, Inherited Blood Disorders etc. All affluent Governments of the world should be able to pitch in with the aid of private hi-tech industries to create the broad base for Informatics. Take Bangalore, India's Silicon Valley for example, it is doing just that.

Identifying centers of expertise is the next step. Each center will draw on its own experience and its collaborators to map out confirmed pathways of signal transduction. This will help in at least two ways- dissemination of information at light-speed and better design of therapeutics. From all of these technologies will emerge reliable and accurate diagnostics.

If you consider all the costs involved in getting information from sources that guard it very tightly we will continue to dwell in the realm of frustration. I will also make another distinction here between having a peer-review panel to validate information in place of a bunch cynical scientists who constantly spin on their own perception of scientific issues.

All of this seems a lot easier when "said" than when actually "done" but that's the way we were 10 years ago!

Cell Signalling Networks Web Tool

Oct 5 2001 11:12AM

Venky Ramakrishna

I was amazed to find an article which describes a web-based tool that allows users to map their own peptide sequences to signalling pathways. The program is called "Scansite" and is pretty straightforward to use. Of course this assumes you have used similar search/pattern finding programs before. I have recently used it and I find the search tool provides exhaustive information on signalling motifs.

Here is the citation to the article should anyone be interested:

Yaffe et al. 2001, "A motif-based profile scanning approach for genome-wide prediction of signaling pathways." Nature Biotechnology, 2001 vol. 19: 348-353.

Those who have no access to the article but still want the program should go directly to

I guess someone else has been thinking in the same direction and in what appears to be an important step towards globalization of informatic tools.

Ready for the Public?

May 8 2001 8:27AM

Ananth Narayanan

I am responding to Venky Ramakrishnas views on the topic mentioned. While I fully endorse his concerns about a single entity monopolizing the information gleaned out of the HG project, it becomes equally relevant to ask whether putting the same in the public domain is really going to work as it is projected. The information is liable to misuse, as would any other information in the public domain.

There is no gainsaying that Genomics research is going to have myriad implications in other branches of sciences, like life sciences. There must be a proper and informed debate at all levels before any meaningful conclusion is made about what is relevant for putting in public domain and what should not be made public.

Dr. T. V. Ananthanarayanan

Protein Isomerases in the Cancer signaling

Nov 18 2002 5:49AM

Nathalie Camsonne

Pin1, a Protein Isomerase discovered in 1995 was found recently to be a close partner of p53 tumor suppressor signaling (Zheng et al, and Zacchi et al in Nature 24 oct 2002). Could we extend this finding to other classes of Isomerases ?