A team of scientists from Centre for Systems and Synthetic Biology (CSSB) headed by Dr Pawan K Dhar has commenced doing research on making proteins from non-coding DNA. The objective of this research was to make proteins from six randomly selected non coding DNA sequences. The initial results of the research has given hopes to the emergence of combinatorial genomics i.e., making user-defined genes towards pre-determined endpoints.
Currently they are building a database that would tell them what to expect, if they expressed a given non-coding DNA sequence. Dr Dhar, director, CSSB informed, "Our preliminary results are very interesting as they strongly suggest that we may be able to make enzymes from non-coding DNA and possibly anti-infective or anti-cancer peptides too. However, to reach that stage it will take at least three more years of research."
According to Dr Dhar before making proteins they had to use bio-informatics tools to compare the candidate sequences with the existing NCBI protein inventory to make sure that these protein sequences were not made by nature.
"Interestingly, one of the artificial genes that we call EKA, derived from EKAM meaning 'first' in sanskrit when expressed resulted in inhibition of cell growth. On switching off the gene, the cell growth was restored. In our experience, this was the most interesting result that encouraged us to move further," he added.
After completing the first phase of the research in RIKEN Advanced Science Institute, Japan from 2006 to 2010, Dr Dhar decided to continue further research in the area of synthetic biology by setting up a new centre on systems and synthetic biology in Kerala. This centre known as the Centre for Systems and Synthetic Biology (CSSB) was established with the help of Kerala government with the aim of developing synthetic biology in the country.
"Kerala government was very generous to provide initial seed money of Rs.3 crore to start the Centre. My guess is that out of this at least Rs.1 crore will be invested on this project."
"Through this research we aimed at questioning the nature's logic that led to the identification of a very fundamental unsolved problem like why nature put start codon and stop codon 'there'? What if we moved the signals elsewhere? Can we go beyond nature's decisions? Etc. That is when we suddenly got the idea of making proteins from non-coding DNA," Dr Dhar said.
Explaining about the whole research he informed that in the first phase, they provided the proof of the concept i.e., one can make proteins from non-coding DNA. Whereas now in the second phase, they must demonstrate synthesis of novel molecules of therapeutic importance. "By using our approach, one would be able to make therapeutically interesting peptides from existing genome, instead of artificially synthesising them in machines. Imagine 98.5 per cent of human genome is non-coding and we have no clue of the treasure it holds."
At present Professor Abhay Harsulkar, head pharmaceutical biotechnology, Poona College of Pharmacy is one of their major collaborators for this research however, CSSB is looking for looking for increased collaboration in this field for better outreach.
Non coding DNA describes sequences that do not code for proteins. The total amount of non-coding DNA varies from species to species. In humans, 98.5 per cent of DNA is non-coding. This includes non coding regions within genes ie introns, pseudo genes that were once protein coding but have lost their ability to code proteins now and intergenic regions or non coding regions between the genes. Although non coding DNA does not code for proteins, part of it is still functional e.g., making ribosomal RNA, transfer RNA and microRNA.