Jill Banfield is a UC Berkeley professor who studies the structure, functioning and diversity of microbial communities in natural environments and the human microbiome. In this “On My Mind” feature, she describes how she first met Berkeley’s newest Nobel laureate, Jennifer Doudna, who gave thanks to Banfield at Wednesday’s press conference.
Back in the early 2000s, my lab was working on developing a method to genomically sample the full diversity of microorganisms in nature. We wanted to circumvent the problem that the vast majority of bacteria had remained unstudied, as they could not be grown in the laboratory.
Our main focus was on pink bacterial biofilms that grow in battery acid-like mine drainage. The research was motivated by the idea that, by understanding microbes in the environment, we could provide new ways to clean up contamination. The method we were developing, called metagenomics, involves sequencing all of the DNA in a sample. This means we get sequences from bacteria, as well as from the viruses of bacteria (which are called phages) that infect them.
‘On My Mind’
We knew little about repeat genetic sequences called CRISPR in genomes, and we were astonished to see that almost every cell of one type of bacteria sampled had a different set of DNA sequences in between the same CRISPR repeats. This was unexpected, because genomes of closely-related bacteria are usually essentially identical to each other in all parts of their genomes.
This variability indicated that the CRISPR regions were evolving extremely fast. Most importantly, we could see that the sequences in between the repeats were little bits of the genomes of the phages that coexisted with the bacteria.
At some point, Kira Markarova published a speculative paper suggesting that CRISPR-Cas is an immune system that works in the same way as RNAi. I was not familiar with RNAi, so I typed ‘RNAi and UC Berkeley’ into a web browser, and Jennifer’s name came up. In fact, today, I redid this experiment, and Jennifer’s name again came up at the top of the list!
I did not know Jennifer at that time, but it was serendipitous that she responded when I reached out to her. When we met in person, I was really surprised — in fact, delighted — that she was clearly excited and willing to start research on the topic. At the time, neither of us were thinking about the applications of these systems — we were just amazed to think that bacteria may have an interference system that was somewhat analogous to that of humans.
For many years, our work took parallel paths: She studied the enzyme mechanisms, and my lab studied how the bacteria-phage arms race shapes microbial communities and the geochemical cycles that they mediate. It was just a few years later that the paper that launched CRISPR-Cas as a genome-editing tool was published by Jennifer Doudna, Emmanuelle Charpentier and collaborators.
Every now and again, Jennifer and I met (usually at the Free Speech Café) and talked about collaborating. A few years ago, my lab’s work had progressed to the point that we could apply metagenomics to even the most complex environments, and we had sequences from many novel CRISPR-Cas systems. So, finally we got to work together to expand the CRISPR-Cas toolbox.
I am simply thrilled by the Nobel award to Jennifer. I think that it is especially well-deserved, not just for the seminal paper, but for the large body of work that she has produced on all aspects of CRISPR-Cas biology and applications, as well as for her international leadership in the field.