In the summer of 2000, Jennifer Doudna and Jamie Cate got married at the Melaka Beach Hotel and two years later they would have their only child, Andrew. At the time Cate was an assistant professor at MIT, but commuting between Yale and MIT was difficult for them, so they decided to search for a way they could work in the same town. Yale tried to keep Doudna on their staff by promoting her and offering Cate a position as well, however, Jamie was uninclined to work at Yale as Tom Steitz was working there in the same field as Cate, and was a competitor to him. Doudna received offers from schools such as Harvard but they eventually decided to go to Berkeley and moved out to California in the summer of 2002. Doudna says that she “connected with Berkeley right away, I had realized that there were opportunities I wanted to pursue scientifically, and a large, diverse public university like Berkeley opens up so many interesting avenues to explore as a scientist.” Doudna’s study of RNA led her to study viruses and more specifically a phenomenon called RNA interference in which small molecules block the transmission of messenger RNA, which is what builds proteins in your body. RNA interference is conducted by an enzyme called “Dicer”, which snips long RNA strands into smaller fragments that can then attack messenger RNA thereby blocking that genetic information from being transmitted. Doudna decided to discover the molecular structure of Dicer. She found “that Dicer serves as a molecular ruler, with a clamp at one end and a cleaver at the other end a set distance away, that produces RNA fragments of an ideal size for gene-silencing.” In her 2007 paper on the structure of Dicer, Doudna discusses how altering a domain in the Dicer enzyme could allow scientists to choose what genes are silenced. “Perhaps the most exciting finding of this study is that Dicer can be reengineered to recognize and cleave specific dsRNA substrates by replacement of the PAZ domain with a different RNA-recognition domain” Despite working on other projects, Doudna would continue to do work with Dicers until 2009. Jennifer Doudna would become a key player in the discovery and development of CRISPR technologies, but before she began contributing research there were a few important breakthroughs that were made. The first CRISPRs were discovered in 1986 by a student at Osaka University in Japan named Yoshizumi Ishino. He found five segments of identical DNA and labeled it as an “unusual structure” in the last paragraph of his 1987 paper. In 1992, Francisco Mojica, a graduate student from the University of Alicante in Spain, would discover the same pattern in a sample of archaea he was studying and refer to Ishino’s paper for more information about them. Mojica was the first person to realize that these DNA segments were related to each other, and in 2002 brought them under one name, which he decided on with the help of a colleague named Ruud Jansen, CRISPR. Mojica also made a major discovery in 2003, which was the function of CRISPR in bacteria. He found that bacteria used CRISPR as a way of protecting themselves against disease by cutting pieces of invading virus DNA and storing it in their own DNA so they could fight back against future invasions from the virus. He struggled to have his findings published as editors deemed it not important enough, but he eventually was able to publish his research in the Journal of Molecular Evolution in 2005. Mojica’s paper led to a wave of research looking into CRISPRs immune capabilities. One popular theory on how it functioned was RNA interference. All this to say that CRISPR was growing fast, and one of the leading theories for how it functioned was RNA interference and Jennifer Doudna was Berkeley’s leading expert on RNA interference. Doudna first heard about CRISPR from a Berkeley professor named Jillian Banfield. Jillian had been trying to sequence DNA but kept encountering CRISPR repeats and, assuming they were related to RNA interference, turned to Doudna for help. They met at the Free Speech Movement Cafe in 2006 and discussed CRISPR. Doudna was delighted to collaborate with Banfield on CRISPR, but she was left puzzled as there was no one in her lab with the right expertise to help her. Enter Blake Wiedenheft, a recent graduate from Montana State University who had a fascination with microorganisms from extreme environments and traveled the world to collect them who also had knowledge of and interest in CRISPR research. Together with Martin Jinek, the crystallography expert in Doudna’s lab, they were able to discover the function of a crucial CRISPR enzyme named Cas1. They found that Cas1 was the enzyme that allowed the bacteria to cleave a piece of DNA from the virus and incorporate it into their own DNA. Their findings were published in June of 2009 in a paper titled “Structural Basis for DNase Activity of a Conserved Protein.” Sources:
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AuthorMy name is Nathan Eberhart. I have a curious mind and am a creative thinker with an interest in biomedical engineering and medical devices. Archives
January 2022
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