The secret life of cells
We get into the world of the single cell with Roger Lasken, Director of Single Cell Genomics at the J. Craig Venter Institute, to find touhow sequencing on a minute scale could radically change the way we understand disease.
A mutation in a single cell can be enough to cause disease. Imagine being able to map those mutations in individual cells, pin pointing the precise source of a disease like cancer, or perhaps even Alzheimer’s disease. Sequencing DNA from single cells opens up a mind-bending array of opportunities for precision medicine and tailored therapies, as well as being an immensely powerful tool for basic biological research. Roger Lasken, Director of Single Cell Genomics at the J Craig Venter Institute, has been driving the sector since the beginning, from the development of techniques for sequencing minute amounts of DNA to figuring out how to make those techniques work for human cells. Who better give us the inside scoop on the exciting world of the single cell?
FLG: Could you tell us a bit more about how you first got interested in science and biotechnology?
RL: Well, early on, I was lucky enough to be in a great lab with Arthur Kornberg. He was at Stanford and he had won the Noble Prize discovering DNA polymerases. I had a wonderful three years at Stanford with him. I learned a lot about these enzymes that synthesize DNA. That was basic academic research looking at the mechanisms at work in bacteria, looking at how their genomes are replicated. Later on I did become interested in biotechnology and I began working at Life Technologies. There are many uses for DNA polymerases, they’re used in amplifying DNA, they’re used in sequencing DNA, and that was my introduction to biotechnology. How do you use those enzymes, for technologies in the lab?
FLG: Your academic career really got going in California. You did your PhD there at the University of Southern California, and then did your postdoc work at Stanford. And now you’re back with J. Craig Venter Institute where you’ve been for the last 10 years or so. What is it about the region that seems so adept at fostering technology development and application? What is it and how was it developed?
RL: It’s just fantastic! California’s wonderful. I’ve been fortunate; I got my PhD at USC, and did a post doc at Stanford. But the rest of the country is pretty exciting too. I was an assistant professor in Cornell Medical School, and then my biotech company, Molecular Staging, where I was Director of Genomics, was founded by Yale professors in Connecticut. Where I am now, in San Diego, is an amazing environment. The J. Craig Venter Institute houses fabulous scientists, and I’m collaborating with people at the Salk Institute, and I’m adjunct in the pharmacology department at UCSD. It’s a wonderful college. It’s just a really vibrant, amazing environment.
FLG: People are increasingly calling San Diego the genomics capital of the world. Is that a tag that you’d agree with?
RL: Yeah, I would. Life Technologies, where I worked for seven years, is a leader in sequencing and then amplification. And of course, Illumina is here in San Diego, an amazing leader in DNA sequencing. So, yeah, I would say right now San Diego is the worldwide hotbed of DNA sequencing technology!
FLG: You’ve been on both sides of the commercial divide. How does working for a not-for-profit, research institute compare to the working environment in a commercial enterprise?
RL: They’re both fascinating approaches to science. I loved my time at Life Technologies and Molecular Staging. You’re thinking about applications, and what kinds of tools can you create. These are tools that are going to facilitate other scientists in their research. We developed the method to sequence single cells; that was a biotechnology approach. Then I wanted to follow that technology into the applications in the research world. My group had developed a method to amplify DNA called multiple displacement amplification (MDA), and then we had won a grant from the Department of Energy to try to develop single cell sequencing. And we succeeded in that, publishing the first work on sequencing from one cell in about 2005. And then I wanted to follow that technology into the excitement of academic research on microbiology and cancer and diseases. So, I went to Allegheny Hospital in Pittsburgh and then onto the J. Craig Venter Institute. Being at a genomic sequencing centre I can really think about where you can take this work. What could you do in terms of sequencing cultured bacteria, in terms of looking at individual cancer cells to see which genes were involved in making these cells cancerous or involved in metastasis? We’re also looking at single neurons now from post mortem human brains and asking what are the mutations involved that can cause disease. We’re also looking at RNA sequencing from single neurons, which genes are turned on and off as neurons perform their functions. So, I’d say in summing up: there’s a lot of excitement in the laboratory tools, developing the biotechnology so we have the tools to make discoveries, and there is a lot of excitement in actually going into the research into diseases and the interesting questions in biology.
Check out the rest of our adventure into single cells on page 46 of the latest issue of Front Line Genomics magazine.