Gene discovery has been a major theme in your career. What motivates you?
Everything we do in my lab and that I’ve done in my career so far has been directed toward figuring out how bacterial pathogens do what they do – how they cause disease. So the gene discovery is directed at that. We try to find virulence genes, genes that are required to cause an infection.
What’s the long view of your work? Are you hoping your work will eventually lead to therapies?
There are two components of the work, one is just basic research and the hope is that we’ll describe a new perspective that gives us a new angle of attack to treat diseases or prevent infections. We also look at transmission of diseases, so we might hope to prevent transmission.
Some of what we do is more applied, and that’s looking at vaccine development. We’re actually developing two different novel vaccines for the two pathogens we work on: S. pneumoniae and V. cholerae.
You published a study a couple years ago that demonstrated that phage can have an impact on the transmissibility of V. cholerae. Do you think there are more interactions like this in other pathogens that we may be missing?
Yes, I think phages are going to be important for many bacterial diseases. That’s been borne out by others in the microbiology field as well.
Do you think phages will be more important factors with environmental pathogens like cholera?
Yes, the environmental pathogens have a lot more exposure to phages, but even S. pneumoniae, which never lives outside the human host, has its own phages as well.
What impacts can phages have on these pathogens?
The obvious things that have been studied are that phages could kill the bacteria. And it’s well known that phages can provide the bacteria with virulence genes, so that cholera genes are actually brought to the bacteria on a phage, so it’s like a gift to the host bacterium. In our work, we’re looking at how the phages might impact the transmission process itself.
What is your lab working on right now?
We have a new type of vaccine that we’re working on – it’s based on outer membrane vesicles. These are vesicles shed by the bacteria; they’re safe in that they’re not living, they don’t have DNA in them, but they work very well as a vaccine. These vesicles have a much more limited set of proteins than a whole-cell killed vaccine, and are really limited to the relevant proteins for a vaccine, so they might work better. If you have too many protein antigens and the host is responding to all of them it doesn’t focus on the few more relevant ones.
You and your colleagues have developed sequencing methods to identify sRNAs. What are sRNAs and why are they important in V. cholerae?
Not only in bacteria, but in humans—and virtually every form of life—people have discovered small, non-coding RNAs, which have regulatory functions. In bacteria they’re called sRNAs. We were the first group to take an unbiased large-scale approach to identifying the sRNAs, and we found hundreds of them. It’s controversial. A lot of people don’t believe our results.
Where do you see your field in 10 years?
This has been beaten to death, but we’re right in the middle of a golden age of advances in sequencing technology, and we’re taking advantage of it. It’s allowing us to come up with new experiments, and it’s also going to have a huge impact on diagnostics in the clinic.
If you had to change careers today and you could do anything, what would you do?
I’ve always loved astronomy – that’s completely different from what I do, at least on the face of it. But there’s a commonality: exploration. Seeing things that have never been seen before or figuring things out about our natural world that haven’t been examined.
What’s your favorite science book?
Arrowsmith by Sinclair Lewis. I’m not sure this counts as a science book, but it was very influential early in my life in steering me towards a career in science.
What is something about you that most people don’t know?
I have six siblings scattered around the country, each smarter than me, yet I was the only one interested in becoming a scientist. An example of our nation's poor development of intellectual resources.