CRISPR: History of Discovery

what does it take to invent the next iPhone or find an exponential n' does it take a genius like Steve Jobs or Alexander Fleming who in their garage or isolated laboratory had a Eureka moment and magically discovered the next big thing what is the formula to discovering the next breakthrough it all begins with observation in 1987 when a group of Japanese scientists discovered an odd DNA sequence in a type of bacteria the e.coli these repeated sequences was something that had never been seen before they are palindromic meaning they read identically forwards and backwards for about 30 bases and are separated by spaces of roughly 36 bases there are not palindromic in nature none of the Japanese scientists were able to elucidate the purpose of these sequences surrendering they simply reported the existence of the sequences and concluded the study some years later in 1990 Francisco mihika chanced upon the same palindromic sequences when he was studying other classes of single cellular organism the archaea they are cousins of bacteria that looked similar but have very different genetic heritage and thus biochemistry like any good scientist mihika consulted scientific literature and saw the Japanese scientists findings excitedly mihika posited that for the same palindromic sequences to be present in both archaea and bacteria the sequences must serve an important purpose he named the sequence s CRISPR clustered regularly interspaced short palindromic repeats focusing on a spaces mihika painstakingly extracted each spacer and inserted them into a bioinformatics analysis tool called blast the basic local alignment search tool hoping to identify these spacers with other known DNA sequences perseverance eventually paid off the spacers were indeed a match with DNA sequences belonging to viruses why would viral DNA end up inside bacteria mihika hypothesized that these spacers and coded instructions for an immune system to protect the bacteria against these viruses meanwhile in 2006 the continued discovery of CRISPR took place in a yogurt production factory that was facing a serious problem the cultures used to produce yogurt were often attacked by viruses causing the cultures to fail a young scientist named Philip Horvath decided to solve the problem he observed that certain strains of bacteria used in a cultures were immune to viral attacks while some other strains could not protect themselves the resistance was not due to cell membrane mutation but was due to virus DNA sequence within the CRISPR of the resistant bacteria Horvath carried out a series of experiments that edit virus DNA segments into that CRISPR array of non resistant bacteria that proved the hypothesis that CRISPR was indeed an adaptive immune system a kind of vaccination for the bacteria against the virus and that immunity dependent on a precise DNA match between the spacer and a target virus going further he identified a gene infront of the palindromic repeats that coded for a protein enzyme called kes 9 which is responsible for cutting virus DNA and hence granting immunity one year later john van der wüste jumped onto the CRISPR bandwagon he was the first to create artificial CRISPR arrays meaning that he could program the CRISPR based immunity directly with any combination of DNA sequence and instruct the CRISPR system to protect the bacteria against any viruses in this way he demonstrated the first case of directly programmable CRISPR based immunity an artificial flu shot for bacteria adding on some years later in manual Charpentier established a full mechanism of CRISPR she accidentally discovered the last essential component of the CRISPR system trans activating crispr RNA or tracer RNA which has an important role in the maturation of the precursor CR RNA into the CR RNA hence in 2012 the field had reached a significant milestone the three necessary and sufficient components are CRISPR who are now known and the discovery was made by 2013 CRISPR had become a rising star in the scientific field and many scientists began studying it accelerating the process of tinkering and application with CRISPR Virginia's sickness successfully moved the CRISPR system from inside the bacteria in vivo to a test-tube environment in vitro while Emmanuelle Charpentier and Jennifer donor focused on optimizing the natural pathway and artificially creates a single guide RNA or sgrna which substitutes the function of tracer RNA and CR RNA now that we know how CRISPR works scientists began working on Crispus real-world applications gene editing several scientists worked on this but the results were merely modest in 2013 funk Jung and George church came along successfully adapting the CRISPR cast line system for genome editing in mammalian cells and optimized the system to edit genes with an unprecedented level of efficiency and accuracy with this it opens up amazing possibilities one day we may be able to design the next generation to be free from diseases and ever stronger and smarter this my friend is the history of the discovery of CRISPR as a gene editing tool from observation to consulting literature hypothesizing proving of hypothesis establishing mechanism tinkering and optimization and finally application so what does it take to discover the next breakthrough and what does it entail find out with us in the next video you

Channel: NIE NTU SINGAPORE

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Length: 6min 43sec (403 seconds)

Published: Thu Nov 23 2017