Infection Medicine, CRISPR-Cas9, Regulation in Infection Biology 
Today’s edition of 12 Women in STEM is slightly different as it celebrates two inspiring scientists: Professors Emmanuelle Charpentier and Jennifer Doudna, who won the 2020 Nobel Prize for Chemistry. Together, they developed an entirely new way of modifying genes, known as CRISPR/Cas, which has allowed scientists to analyse the function of individual genes in individual cells in the lab, in plants and even in whole animals.
Professor Emmanuelle Charpentier was born in 1968 and knew from an early age that she wanted to work in an area where she could advance medicine. After obtaining a degree in biochemistry, microbiology and genetics at the Pierre and Marie Curie University in Paris and a PhD at the Institut Pasteur, she spent most of her time working on disease-causing bacteria, before starting to run her own lab at the University of Vienna. While there and at Umeå in Sweden, she started to work on an unusual section of the genetic code in a bacterium called Streptococcus pyogenes; this section is called CRISPR and contains short sections of DNA that have been copied from viruses that infect bacteria. Microbiologists knew that CRISPR was involved in a type of bacterial immune defence against viruses and leads to invading DNA being chopped up to disable the virus, but they didn’t know exactly how it did this. Charpentier and her lab discovered that the bacteria used CRISPR genes and another gene called tracrRNA, which codes for an RNA molecule rather than a protein, to target the genetic code of viruses that attacked the bacteria. The next step was to figure out how this system could cut the virus DNA.
While Charpentier was working on bacteria, Professor Jennifer Doudna had become an expert in the biochemistry of RNA molecules. Born in 1964, she grew up in Hawaii and as a child was inspired to become a scientist after reading a copy of The Double Helix by James Watson, one of the discoverers of the structure of DNA. She studied for a degree in biochemistry at Pomona College in California and followed this with a PhD from Harvard School of Medicine. During her career, she researched RNA molecules that can act in similar ways to proteins, opened her own lab at Yale University and then moved to the University of California, Berkeley. Doudna had also become interested in the CRISPR system before she and Charpentier met at a scientific conference in San Juan, Puerto Rico in 2011. Here, they discovered their common interest in how CRISPR works and decided to work together to investigate how S. pyogenes cuts up virus DNA after using CRISPR and tracrRNA to recognise the viruses.
Working together, Charpentier and Doudna discovered that this required a protein called Cas9, a type of protein that can cut DNA like a pair of molecular scissors, and that the CRISPR/tracrRNA system guided Cas9 to the virus DNA. Excitingly, they also showed that they could re-programme this system to target any gene they chose, allowing scientists to switch off the gene or modify its activity to investigate its function. Based on their ground-breaking discovery, other scientists have since shown that this system can be used in cells grown in dishes in the lab, in plants and even in experimental animals, to investigate how individual genes work. Changing gene function and activity could be done before CRISPR/Cas9, but it was slow and difficult; Charpentier and Doudna’s discovery made this process quicker, easier, more accurate and was truly revolutionary.
Since their discovery, both Emmanuelle Charpentier and Jennifer Doudna have set up companies to develop CRISPR/Cas9-based treatments for human diseases, and Doudna is also leading a COVID-19 diagnostic lab at UC Berkeley. Although they have both fulfilled their childhood ambitions of understanding nature and advancing medicine, they continue to carry out research and inspire other people.