Your work seems to center on Legionella. What gets you excited about working with this organism?
L. pneumophila is an environmental microbe that co-evolved with amoebae and protozoa, which eat and digest bacteria. It’s remarkable that the survival tactics that Legionella acquired in the environment also equip the bacteria to replicate in resting human macrophages. As a result, Legionella is a great experimental tool to apply bacterial genetics to study fundamental biological questions, including mechanisms of innate immunity and bacterial differentiation.
You've found that L. pneumophila links the expression of certain virulence factors to the production of an alarmone called ppGpp. What is an alarmone and why does the need for an alarmone coincide with the need for virulence factors in L. pneumophila?
Decades of research established alarmone, or “magic spot”, as a second messenger that a wide variety of bacteria rely on to coordinate expression of traits that increase resilience to stress. When nutrients are scarce, ppGpp cues Legionella to activate traits that promote its spread to a new replication niche.
You earned your Ph.D. in 1991. How has our understanding of L. pneumophila evolved over the course of your career so far?
I joined the field when just a few labs had begun to develop genetic methods to analyze Legionella growth in macrophages, which had only been described using electron microscopy. Thanks to efforts by several groups, we now have a panel of modern tools to manipulate the gene expression profile of both the pathogen and the host, and to study their interaction with sensitive fluorescence methods. Now the field can exploit Legionella to ask fundamental questions that are relevant to many microbes.
Where do you see your field in 10 years?
The field is heavily focused on how L. pneumophila survives and replicates either in macrophages or in nutrient-rich medium. Methods are now available to take a more broad view by investigating how Legionella thrives in fresh water supplies, which are the source of outbreaks. I expect we’ll have a much clearer view of the pressures and mechanisms that drive evolution, virulence, and diversification of the Legionellae.
If you had to change careers today and you could do anything, what would you do?
A real luxury would be to earn a living as either a travel or food writer.
What’s your favorite science book?
In my free time I rarely read science. Currently I’m reading Frank Bruni’s memoir “Born Round”. I love his sharp eye and even sharper writing, whether the topic is his upbringing in a large Italian family, a particular restaurant, or current affairs.
What is something about you that most people don’t know?
I credit competitive team sports with starting me on the path to a career in academic science. I was a three-sport athlete in high school, when Title IX became law and created new opportunities for female athletes. I was fortunate to attend a summer camp in Michigan where I met Yale’s field hockey coach, who encouraged me to apply. I just attended my 30th college reunion—the people I met there continue to inspire me to think big and to give back.