Jagesh Shah: A quantitative approach to cell biology

Q uantitative approaches are becoming an essential part of modern biology research. For example, systems biologists construct models of complex biological systems to help fl esh out conceptual frameworks and to gauge the completeness of our current understanding of those systems (1). Such quantitative approaches come naturally to Jag-esh Shah (2). Shah fi rst trained as an engineer— working on man-made systems—before becoming enthralled by the ones nature built (3). In his lab at Harvard, Shah uses modeling to guide his inquiries into cell behavior (4, 5). We called him to talk about his career and to fi nd out what the mitotic spindle checkpoint and cilia have in common. Why did you do your undergraduate and graduate work in engineering? I was probably inspired by my father, who is an engineer. As a kid I spent a lot of time with him taking things apart and putting them back together. I was interested in how technology works, so, when I went to college, I studied computer engineering. I liked what I was studying academically, but having spent time in industry I didn't want to work there. I wanted to do more theoretical work, so I decided to go to graduate school. I had taken biology in high school, but I wasn't very excited about it at the time. It wasn't until the early part of graduate school that I really got hooked into biology. What got you hooked? For graduate school, I had found a joint program administered between MIT and Harvard where you did your PhD in engineering at MIT and medical school classes at Harvard Medical School. To prepare, I took a freshman biology class, and almost every piece of information transmitted to me by the professors was new to me. It was a transformative experience. As an engineer you could say, " I know how a computer works, and I could in principle build one and explain to you how it works. " But then somebody shows you a neutrophil crawling around after a bacterium, and you think, " How the heck does that work? " I was absolutely blown away. I couldn't even imagine writing a program to do the things that a cell does, let alone the program in the cell's nucleus that makes a whole human being. What's the design principle underlying that? At that point, I thought, " This is what I …