The 2020 Millennium Technology Prize, introduced in May, has been awarded to Shankar Balasubramanian and David Klenerman, “for their development of revolutionary DNA sequencing techniques.” Their work is an ideal mix of science and innovation, and really apt as we’ve all heard a fantastic deal about genome sequencing within the context of the continuing pandemic.
Emphasis on innovation
Awarded by the Republic of Finland, together with prime Finnish educational establishments and industries, The Millennium Prize has a twenty first century outlook, with a powerful emphasis on innovation. Past winners embrace Tim Berners-Lee (for implementing the world-wide internet) and Frances Arnold (for her work on directed evolution in a laboratory setting). Three of the eleven awardees to this point have subsequently gained Nobel prizes. We wait, with bated breath, for Balasubramanian and Klenerman!
Shankar Balasubramanian was born in Chennai, and has lived in England for many of his life. After his PhD, he joined the Chemistry Department, Cambridge University. He teamed up with David Klenerman, recruited by the Department across the similar time. The preliminary intention was to construct a microscope that might observe single molecules. Of particular curiosity to him was the molecular equipment that DNA makes use of to make copies of itself. Somewhere of their discussions arose the germ of the concept for a brand new strategy to learn the alphabet that make up DNA, and to thereby entry the knowledge saved in them.
DNA (or RNA, in some viruses), the genetic materials of life kinds, is made of 4 bases (A, T, G and C; with U changing T within the case of RNA). A chromosome is the duplex of an extended linear chain of those – and within the DNA sequence is info – the blueprint of life. Life famously can replicate, and DNA replicates when an enzyme, DNA polymerase, synthesises a complementary strand utilizing an current DNA strand because the template.
Breakthrough thought
The breakthrough thought of Balasubramanian and Klenerman was to sequence DNA (or RNA) utilizing this means of strand synthesis. They cleverly modified their ATGC bases so that every shone with a distinct color. When copied, the “coloured” copy of DNA might be deciphered from the colors alone, utilizing miniature optical and digital gadgets.
A really important advance of their “Next Generation Sequencing” (NGS) technique lies within the dimension of DNA that might be sequenced at one go – greater than 1,000,000 base pairs could be sequenced, which interprets to a whole bunch of genes and even the entire genome of an organism. This is made potential by concurrently sequencing a whole bunch of items of DNA on the similar time. Many copies of this lengthy DNA “sentence” are randomly damaged up into small items, every no quite a lot of hundred bases lengthy, that are all sequenced collectively. The “reads” are then fitted collectively, within the method of a puzzle, to offer the ultimate sequence.
This know-how was spun off as a business entity, Solexa, with the initiative of Balasubramanian and Klenerman. This phenomenally profitable startup was later acquired by the biotech firm Illumina.
Falling value
What about the price of all this sequencing? When the Human Genome Project delivered the primary, near-complete sequence of our genome, the price was estimated to have been 3 billion {dollars}. As all our chromosomes collectively have 3 billion base pairs, it turns into a simple calculation – One greenback per sequenced base. By the yr 2020, Next Generation Sequencing applied sciences had pushed the value for sequencing your genome all the way down to a thousand {dollars} – when this know-how turns into prevalent in India, this sum ought to grow to be just a few 1000’s of rupees!
To assume {that a} coronavirus genome has not 3 billion however 30,000 RNA bases – not surprisingly, this has resulted in an explosion of information on the genomes of the novel coronavirus and its variants. Health authorities within the United Kingdom have sequenced the viral genome of 1 out of sixteen individuals who have examined Covid-positive. The fashionable genomic knowledge sharing web site GSAID has over two million submissions of Cov-2 genomic sequences, from 172 nations. NGS has been on the coronary heart of monitoring the unfold of viral variants throughout the globe, and tracing the supply of outbreaks.
Shankar Balasubramanian continues to run a positive laboratory, targeted on the design of therapeutic molecules that may tune down the uncontrolled expression of sure genes, and so management the harm they trigger in situations akin to most cancers.
(This article has been written by D. Balasubramanian in collaboration with Sushil Chandani who’s an expert computational biologist, sushilchandani@gmail.com )
dbala@lvpei.org