Good Read (1): Scissors for DNA

DamenC
5 min readMar 7, 2023

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I always wanted to create a space that stores a summary of some of the research papers, lecture notes, and talks that I came across. Well, no one can remember everything they consumed, so I decided to share them here under "Good Read". May some ideas inspire you!

The first thing I want to share is some lecture notes that I took after watching Emmanuelle Charpentier and Jennifer A. Doudna's Nobel Lectures. They won Nobel Prize in Chemistry 2020 for their work in the development of the CRISPR-Cas9 gene editing tool.

This revolutionary technology allows scientists to easily and accurately make changes to the DNA of living organisms, enabling a wide range of applications in medicine, agriculture, and biotechnology. The ability to precisely target and edit specific genes has enormous potential for treating genetic diseases, developing new crops and medicines, and understanding the fundamental biology of living organisms.

In this post, I will extract the similarities and differences on their interest, vision, approach, and contribution to this pioneering work.

Research Interest:

The similarity is that both scientists found their passion in understanding how CRISPR-Cas9 targets and makes changes to DNA sequences. The difference is that Emmanuelle Charpentier originally found her interest in the interaction between bacteria and their environments, particularly in the context of human infections. Jennifer Doudna found her interest at a biochemistry level. She was interested in CRISR Cas system from the very beginning.

For Emmanuelle Charpentier, the research on CRISPR-Cas9 originates in her deep interests in understanding how bacteria interact with human hosts and how the host can defend against bacterial infections. She recognized that in order to investigate these mechanisms, it was necessary to study the regulatory mechanisms that use proteins and smaller RNAs that are involved in bacterial pathogenesis. However, to study these mechanisms in depth, it was necessary to have precise genetic tools that could be used in human cells. With this in mind, she decided to develop the CRISPR-Cas9 system, which is a revolutionary genetic scissors that can recognize specific sequences on the DNA and has the ability to cleave them.

For Jennifer A. Doudna, her interests originated in uncovering the function of the protein called CRISPR-Cas9. It had been previously shown by Emmanuelle Charpentier’s research group that the organism Streptococcus pyogenes, which infects human beings, contains the CRISPR-Cas9 protein. This protein has been encoded in its CRISPR system and is implicated in the protection of cells from viral infection. Doudna was particularly interested in understanding how CRISPR-Cas9 was able to provide this protection.

Vision:

The similarity is that both scientists recognize the potential of this genetic editing tool to be applied in various fields, including medicine, agriculture, and biotechnology. They are both excited about the possibilities that this technology holds and anticipate further discoveries in the diversity of the CRISPR-Cas system in the future. The difference is that while they are both excited about the future of genome editing, Jennifer Doudna expressed more concerns on the ethical and societal issues that this technology could bring.

The CRISPR-Cas9 system has been classified into two classes, each with its own supporting systems and subsystems. However, Emmanuelle Charpentier anticipates that further diversity within the system will be discovered in the future, thus expanding the CRISPR-Cas9 toolbox. She believes that the potential applications of genome editing technology are vast, particularly in fields such as life science and biology. Additionally, Charpentier highlights that this is an exciting time for young scientists to pursue research in genetics as technologies such as CRISPR-Cas9 have opened up new opportunities for studying cells and organisms that were not possible 15 to 20 years ago.

Jennifer Doudna envisions that the CRISPR-Cas9 system has the potential to be used for both fundamental research and exciting applications in various fields, including public health, agriculture, and biomedicine. She emphasizes the potential significance of genome editing on germ cells, as these cells have the ability to differentiate into many different cell types. However, she also acknowledges the ethical and societal issues that are raised by the possibility of genome editing on germ cells and the need for responsible use of the technology. Additionally, Doudna notes the diversity of CRISPR systems in nature and highlights the discovery of CRISPR-Cas13, which is effective at detecting RNA molecules. This discovery has further sparked interest in the biochemical activities of other families of CRISPR-Cas proteins.

Approach:

The similarity is that both scientists have conducted laboratory experiments in their research on CRISPR systems. The difference in their approaches is that Emmanuelle Charpentier has placed a greater emphasis on literature review of previous studies on CRISPR systems, while Jennifer Doudna has focused more on utilizing computational methods to visualize the three-dimensional structure of the Cas9 protein.

In her lecture, Emmanuelle Charpentier emphasizes the importance of literature review in her research on CRISPR systems. She explains that when she initially began working on CRISPR systems in her lab, she conducted an extensive review of existing publications on the subject. This review helped her to understand the differences between the CRISPR-Cas9 system and other CRISPR-Cas systems. Through her review, she discovered that the genome of the streptococcus paragenesis genes belonging to the CRISPR-Cas9 system had not been studied at the molecular level. This led her to conduct laboratory experiments to describe the molecular mechanism by which the CRISPR-Cas9 system recognizes and targets viruses.

Jennifer A. Doudna’s approach in her discovery of the CRISPR-Cas9 system utilized a combination of computational biology and biochemistry. Together with her team, she employed x-ray crystallography to determine the three-dimensional structure of the Cas9 protein and conducted experiments to understand its interactions with the CRISPR RNA and target DNA. Through this approach, they were able to gain a comprehensive understanding of the function of the bacterial enzyme Cas9 and to develop strategies for engineering it as a simple two-component system for directing DNA double-stranded cutting. This combination of computational biology and biochemistry allowed them to gain the insights needed to develop the CRISPR-Cas9 as a powerful genome-editing tool.

Contribution:

The similarity in the contribution of both Emmanuelle Charpentier and Jennifer A. Doudna is that they both played a crucial role in the discovery and early development of the CRISPR-Cas9 system as a genome-editing tool. Both scientists contributed to the characterization of the molecular mechanisms underlying the CRISPR-Cas9 system, and they both have been instrumental in advancing the field of genome editing.

The difference in their contribution is that Emmanuelle Charpentier’s work primarily focused on the discovery of the molecular mechanisms of the CRISPR-Cas9 system and the characterization of the CRISPR-Cas system from the Streptococcus thermophilus. On the other hand, Jennifer A. Doudna and her team have been more focused on the engineering and application of the CRISPR-Cas9 system as a genome-editing tool.

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DamenC

MS in Informatics; MA in Area Studies. Interested in using AI for sustainable development of nature and human societies. Contact me at: s2226089@u.tsukuba.ac.jp