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Proteins provide the clue to new drugs, therapies and diagnostic tools

Our Bureau, HyderabadMonday, February 24, 2003, 08:00 Hrs  [IST]

If DNA is the blueprint to build the complex machine that is a human, then proteins are the parts of the machine that make it work. With the completion of the first draft of the DNA sequence that makes up the human genome, the challenge facing medical research is to understand gene function. Proteomics provides a biological tool, or assay, for understanding gene function, and development of new drugs, new therapies and new diagnostic tools, according to speakers at a two-day symposium on Proteomics in Hyderabad from Sunday. The symposium is organised by the Association for the Promotion of DNA Fingerprinting and other DNA Technologies as part of the 7th ADNAT Convention and CCMB (Centre for Cellular and Molecular Biology) to coincide with the 50th year of the discovery of DNA Double Helix by Francis Crick and James Watson. In his talk on "Before, During and After the Discovery of DNA Double Helix," Dr P M Bhargava, former CCMB Director and Chairman of ADNAT, recalled that he heard a lecture by Francis Crick on the structure of the DNA, the genetic material, in 1954, and it was so simple. DNA was, according to Crick, a double helix with a complementarity rule and that the sequence of the four building blocks of DNA in any of the two strands would determine the sequence of the building block in the other strand. The simple, double stranded helical structure proposed by Crick and Watson for DNA, following this rule could easily explain three important phenomena, the phenomenon of inheritance, the phenomena of mutations and their inheritance, and how DNA might control the sequence of amino acids in proteins. This was about the time that Fred Sanger, at Cambridge, was sequencing the first protein, Insulin. Dr Bhargava said the scientific community then was divided equally into two groups - one that was greatly impressed by the simplicity of Crick's model and the other that was cynical about Crick being right as the model looked too simple. How could such a complex set of problems have such a simple answer? A few years later, Matt Messelson and Frank Stahl did their famous experiment and finally Watson and Crick's model of DNA received its stamp of validity. "When we are celebrating the golden jubilee of the most beautiful discovery of the structure of DNA, we are concurrently celebrating many other things. And let me list three things - the power of model building, the value of global view of knowledge and the relationship between science and aesthetics. The structure of DNA has the golden ratio (1:168) built in it," Dr Bhargava said. Sam Hasnah of the University of Michigan wanted India to join the Human Proteomics Organisation (Hupo). The objective of Hupo was to promote initiatives in proteomics that are intended to benefit both the public and the private sectors. The initiatives identified were aimed at resources and technology development, proteome informatics, comprehensive analysis of human serum and plasmas well as model cells and tissues, he said. Dr Lalji Singh, Secretary of ADNAT and Director of CCMB, in his welcome address, said the human genome project had resulted in an explosion of DNA sequence information that had opened up new possibilities for a better understanding of human health and disease. In the post-genome era, one can study not only the function of specific genes and their protein products, but also how the interplay between genes controlled a given physiological context. There was a great deal of interest in proteomics as a means of generating new and potentially comprehensive molecular information associated with specific biological conditions. At the technical sessions that followed, Dr Pierre S Paroutaud from France, said proteomics had the potential to revolutionise the development of new drugs, new therapy and diagnostics. For the human genome, with approximately 3 billion bases, the genes represented only 3 per cent of the genome (40,000 genes). While genome is finite, proteome is just the opposite as proteins are more complex and dynamic. Proteins can be very unpredictable as they are capable of changing their structure according to time, temperature and other factors. "If the genome represents the words in the dictionary, proteome provides the definitions of these words. The patterns of how these proteins interact with each other, with their environment, and with other molecules, provide the grammar and syntax to form sentences and a meaningful language. Theses interactions define an individual's state of wellness or disease," he said. Proteomics provides the understanding of what is going on in the body and therefore allows development of new drugs, new therapy and new diagnostic tools etc. The speakers at the two-day symposium included Richard Simpson from Melbourne, Australia, Detlev Schleuder, Dramstadt, Germany, David J Munroe, Frederick, USA, Akhilesh G Pandey, John Hopkins University, Baltimore, USA, Uwe Vollkopf, Uberlingen, Germany, Ashok R Dongre, Pharmaceutical Research Institute, Princeton, USA, Tom Slyker, Hercules, USA, Yadunanda Kumar and Utpal Tatu, Indian Institute of Science, Bangalore. Ravi Sirdeshmukh of CCMB, who was the convener, gave an overview of the symposium. Simultaneously, ADNAT is also holding a training course at the CCMB campus. Young scientists from academic institutions, medical; and industrial R&D organizations and from bioinformatic companies are attending the course.

 
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