Making Sense of a Complex Situation

 

“The world of biology is incredibly complex,” says Dr. Jasmin Fisher, who holds appointments at Microsoft Research, in Cambridge, UK, and Cambridge University. “The hand-drawn diagrams of biological processes I first learned to produce are static illustrations; they often don’t provide much insight into the highly dynamic interactions that occur. That is why I opened myself to the world of computation.” Today, Fisher is considered a world leader in a rapidly growing field of biological research in which computational models are the impetus for new discoveries.

Fisher came to the Weizmann Institute for her doctoral studies after completing a B.Sc. and M.Sc. in biology at Ben-Gurion University of the Negev. It was at Ben-Gurion, she says, that her adviser, Prof. Shai Silberberg, imparted the basics of science that she still applies every day: “Be a perfectionist in your work and learn to ask the right questions.”

At the Weizmann Institute, Fisher conducted her Ph.D. research in the neurobiology group of Prof. Michal Schwartz, investigating the dialog between the immune system and the central nervous system. Among other things, research in the group was changing ideas about the protective role that certain immune cells play in the brain and nervous system. In Schwartz, Fisher found an insistence on thoroughness that fit in with her own inclination, as well as a role model of an accomplished woman scientist.

Along the way, Fisher was coming to understand that the processing power of computers was needed to help life science researchers deal with the complexity of even the simplest living systems. So she stayed on at the Institute to conduct postdoctoral research with Prof. David Harel of the Computer Science and Applied Mathematics Department. In the 1980s, Harel had developed a visual programming language called Statecharts to deal with specifying and developing such complex systems as avionics. But he and others soon realized that biological systems could be described in much the same way as air-flight systems, and began applying tools like Statecharts to cells and organisms. “Because Statecharts is a visual language, it is easy for a non-programmer to use. Because it is state-based, it is an intuitive tool for describing biological mechanisms,” says Fisher. She joined the effort under way in Harel’s group to use computers to map out developmental processes in the nematode C. elegans, a model lab organism.

Her research took her next to Switzerland, to further her training in computational methods in the group of Prof. Thomas Henzinger at the Ecole Polytechnique Federale de Lausanne. There, she invented the term “executable biology” to describe the kinds of models that simulate biological processes, and she and Henzinger argued that such computer-based research could not only help scientists make sense of complexity, it would bring a precise, formal, quantifiable approach to the life sciences. “A computerized model begins with a hypothesis. When you organize the experimental results in the same formal language as the model, you can compare the two and immediately see the gaps. These gaps then enable you to refine your model and design new experiments,” she says.

As Fisher was finishing her work with Henzinger, Microsoft Research in Cambridge was adding biology to its list of computational research subjects. Fisher was invited to join the Programming Principles and Tools group there, and was later offered a position as a research group head at Cambridge University.

 
Nowadays, Fisher engages in long-term collaborations with experimental groups to continue investigating cell decision-making processes. In one of those collaborations, she works on understanding how blood cell development goes awry in leukemia. In another, she investigates cell signaling in C. elegans – research that has implications for understanding cancer.  This signaling has been preserved throughout evolution, up to and including humans. Recent findings in her group demonstrated the benefits of repeated cycles of computational modeling, prediction and experimentation. They revealed a crucial molecular mechanism by which developing cells synchronize their cell cycles and then break that synchrony to continue developing toward individual cell fates.

Eventually, says Fisher, her group and others working in the field will produce a broad, common platform for computational biology, and its tools will become standard in the life sciences – akin to the use of microscopes and DNA sequencing equipment today.

Though her rise in the field has taken her out of the country for over a decade, Fisher, a seventh-generation Israeli, admits it has been hard to be away. “The Weizmann Institute still feels like home to me,” she says. Conducting research there has always been a source of pride for me.”