So who won this year's most prestigious honor in Chemistry??

 

On 7th October it was honored to Emmanuelle Charpentier of France and Jennifer Doudna of the U.S. for discovering a gene-editing technique called CRISPR- Cas9 DNA snipping "scissors", one of gene technology’s sharpest tools: the CRISPR/Cas9 genetic scissors.

 

What is it about??

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Genome editing is a technique where the DNA is cut by an enzyme to edit or repair or make specific changes of a cell or organism. So how did this technique reach to win the most prestigious award. CRISPR is a gene editing technique where researchers can use these to alter the DNA with extremely high precision. Noble Jury quoted this "This technology has had a revolutionary impact on the life sciences, is contributing to new cancer therapies and may make the dream of curing inherited diseases come true." Once scientists learned how the CRISPR system worked in bacteria, they figured out how to reprogram it to allow efficient editing in any species. This revolutionary breakthrough has completely changed the way science is performed, and it will soon change many aspects of our everyday lives.

 

CRISPR (clustered regularly interspaced short palindromic repeats). These play an important role in microbes immunity. When a virus infects a microbial cell, the microbes will install a CRISPR-associated nuclease (Cas9) to cut off a piece of the viral DNA. The nuclease enzyme moves towards the target sequence with the help of a target sequence called guide RNA(gDNA), which is complementary to the viral genome target fragment. The special DNA fragments will be then stored between the palindromic CRISPR sequences to retain genetic memory for avoiding and future infections from the same strain. The interesting thing is that the unique, non-repetitive sequences in CRISPR appear to match the genetic code of various viruses, so the current thinking is that this is one part of an ancient immune system that protects bacteria and archaea from viruses.  

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How did this start?

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Emmanuelle Charpentier  being a very enthusiastic researcher was intrigued by pathogenic bacteria and she had numerous questions about its survival, resistance, and how to tackle them? 

In 2002,she started her own research group at the University of Vienna, her main focus was  on one bacteria that infects millions of people every year causing infections like tonsillitis and impetigo- Streptococcus pyogenes., even though they were easily treatable, they could cause life threatening sepsis by breaking down the soft tissues in the body, terming it as flesh eater, and a threat to mankind. She tried understanding how the genes are regulated in the bacteria  and this led to the discovery of an unknown molecule called tracrRNA, which was a part of the bacterial immune system and it helps the bacteria to destroy viral DNA. This was the first step towards the discovery. 

Jennifer Doudna, from a young age being intrigued on how scientific mysteries are solved, started solving RNA based scientific mysteries. Her immense knowledge on RNA interference and a call from a colleague, puzzled her that there are repetitive DNA sequences that are surprisingly well preserved. The same code appears over and over again, but between the repetitions there are unique sequences that differ. She went on to map this machinery, and her sense of molecular machinery comes to life through the CRISPR system. Then she makes a team to understand  the proteins related to this system called cas, their functions and do they cleave? Their mapping explains that bacteria’s immune systems can change is categorized as class 1 where it is a complex machinery that requires many different Cas proteins to disarm a virus. The class 2 systems are significantly simpler because they need fewer proteins. Jennifer Doudnathey, she succeeded in recreating the bacteria’s scissors and reprogramming it

 

The beginning to a partnership!!!

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A coincident meeting in a cafe can stir up ideas leading to Nobel prize!!! 

The scientist duo met at a cafe on the second day of a conference, and are introduced to each other and the following day Doudna proposes the idea of exploring the old parts of the capital city, as they strolled around they started discussing about their research and Charpentier wondered whether a collaboration can be made and the rest is history!!!!

 

They had numerous digital meetings for planning and understanding the system. There hypothesis was CRISPR-RNA is needed to identify a virus’ DNA, and that Cas9 is the scissor that cuts off the DNA molecule. However, nothing happens when they test this in vitro. After a lot of failed experiments and brainstorming, they came to understand that Cas9 had access to tracrRNA and that cleaved the DNA into parts. They together proved the use of these scissors to cut any DNA molecule at a required site.

 

The modifications-

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After this massive discovery, they planned to simplify it. They fused the tracr-RNA and CRISPR RNA into a single molecule called guide RNA. To check its efficiency they took a gene already present in Doudna’s laboratory and chose 5 different places where it should be cleaved. They prepare the CRISPR system so the code matches the code where the cut has to be made and for their astonishment it worked, and cleaved at the exact right places with guide RNA. 

Charpentier and Doudna had uncovered a fundamental mechanism in a bacterium which was a revolutionary in the field of science that could help curing various diseases. 

 

This tool has been used in plant breeding techniques to modify the plant genome for antibiotic resistance genes (to avoid antibiotic resistant microbes) , genes for avoiding heavy metal absorption by rice (betterment of crop quality) and also genes that can thrive drought conditions and resist from insects (to avoid pesticides)

 

Now this system is being used in the medicinal field. These genetic scissors are being used in immunotherapeutic for cancer and also in hope to cure genetically inherited diseases. They are carrying out clinical trials and checking whether they can use CRISPR/CAS9 to treat sickle cell anemia, beta thalassemia and other inherited diseases. Animal studies have shown promising results that the genetic scissors have helped in treatment of inherited diseases such as muscular dystrophy, spinal muscular atrophy and Huntington’s disease by repairing the genes in brain and muscles but it might need some refinement before testing on humans,

 

Hear from the Nobel laureates -

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Emmanuelle Charpentier published the discovery of tracrRNA in March 2011. She knew that this was an exciting piece of research and with her many years of experience in microbiology she needed a biochemist for her continuing research on this system. Jennifer Doudna was her natural choice, and hence that spring, when Charpentier was invited to a conference in Puerto Rico to talk about her findings, her aim was to meet this skilled Berkeley researcher.  Jennifer Doudna quotes “We had a sense that we were onto something big,” says Jennifer Doudna, as she recalls the start of her “curiosity-driven” research into CRISPR and reflects on the pace of the field today” .

 

Prof. Charpentier said that she considered herself "a scientist" first, but hoped the prize would provide "a really strong message for young girls". Prof. Doudna hopes this can be an encouragement to other women. “Sometimes,” she comments, “there’s a sense that no matter what they do, their work will not be recognized in the way it would be if they were a man.” and proudly these two have been successful in breaking those stereotypes .

 

Emmanuelle Charpentier always follows the word quoted by Louis Pasteur “Chance favors the prepared mind”. Her hunger for new discoveries and her free and independent thought process has governed her path for this research. 

 

These two are an inspiration to many young women researchers to not let go of their passion, however hard it gets. Be mindful of ideas, free and enjoy the path of science, which will lead you to various important and path breaking findings, which can serve humanity. Their 8-9  year long startling discovery has finally led to winning the most prestigious Nobel prize and we congratulate them for this amazing feat and for many more.