January 16, 2014

Synthetic and Systems Biology: Reinventing the Code of Life

A panel at the Helix Center, titled "Synthetic and Systems Biology: Reinventing the Code of Life included Columbia University professors Saeed Tavazoie and Andrea Califano, as well as Michael Hecht (Professor of Chemistry, Princeton University), Mark Fishman (President, Novartis Institutes for BioMedical Research), Christopher Mason (Assistant Professor of Physiology and Biophysics, Institute for Computational Biology, Weill Cornell Medical College), and Michael Waldholz (Medical Science Writer and Media Consultant).

Advances in genomics and the development of new technologies over the past decade have given biologists the ability to engineer DNA to perform specific functions. This emerging science, called synthetic biology, holds great potential for a number of applications, and experiments have already been done to reprogram algae to produce biofuels, design bacteria that can sense and consume toxic substances, and use living cells to manufacture compounds that can be used as drugs.

Synthetic biology has emerged in parallel with systems biology, but in many ways the two sciences are closely intertwined. As systems biology improves our mechanistic understanding of how biology functions at the molecular level, synthetic biology is taking this knowledge to push biology in new directions, from synthesizing molecules using biology all the way to synthesizing new forms of biological life.

In a public roundtable discussion at the Helix Center in New York City, Columbia University Department of Systems Biology professors Saeed Tavazoie  and Andrea Califano  joined a panel of experts in discussing the intersection of systems and synthetic biology, and the role that these two disciplines will play in the development of the biological and biomedical sciences in the coming years.

One of the goals of systems biology is to reveal the underlying principles that govern how cells work. Rather than looking at single genes, systems biology approaches the molecular world from the perspective of how all the components that drive a cell — genes, RNA, proteins, and interactions among all of these parts — give rise to observable phenotypes. Within the context of synthetic biology, systems biology is critical, because in order to engineer something new and know how it will behave, you need to understand how these underlying systems work.

As Dr. Tavazoie explained, “The real challenge nowadays … is to understand biological systems in ways that are more similar to how physicists think about systems; that is, to be able to predict the dynamical trajectory of a system in time, know it well enough to understand it. That’s the challenge and the goal that we’re shooting for.”

This ability to predict how changing the molecular building blocks of an organism will affect its behavior is particularly important considering concerns that some critics have raised about the potential for synthetic biology to be used for malicious ends or to accidentally create dangerous, never-before-seen forms of life that can not be controlled.

"The degree to which synthetic biology is going to be successful... depends on a foundational understanding of how cells work. That's where systems biology comes in."

According to Dr. Tavazoie, systems biology will be critical to resolving these concerns. “The degree to which synthetic biology is going to be successful and people are going to rely on it … depends on a foundational understanding of how cells work. That’s where systems biology comes in. One of the major challenges for us is to understand these systems well enough to predict exactly what happens if you reengineer a particular molecule in the cell and what the consequences are when you put it back into the very complex, multiscale system that is the human body.”

At the same time, Dr. Califano pointed out, synthetic biology is becoming an increasingly powerful tool within the context of systems biology, providing methods for testing computational models of biological activity in the laboratory. “We always think that understanding biology informs the ability to engineer it, but actually the ability to engineer it also helps to dissect it.” Describing work by Diego di Bernardo (currently a Research Assistant Professor at the Telethon Institute of Genetics and Medicine in Naples, Italy) to engineer a biological circuit in yeast that was used in the DREAM Challenges , he explained, “Having an engineered system that can not interact with the environment was incredibly important because if you can reconstruct the logic of the circuit, you know that your [computational] method works well. Beforehand there no way to know whether the method was able to reconstruct it… There’s an entire new discipline in synthetic biology that will help systems biology to dissect regulatory models.”

Because systems biology and synthetic biology are still relatively new sciences, the speakers anticipated that the relationship between the two will become clearer as they are increasingly applied to solve biological questions. Dr. Tavazoie predicted, “We have just begun to scratch the surface of the kinds of potential interactions that can happen, and I think synthetic biology and systems biology are going to be closely interacting with each other as they co-evolve.”

— Chris Williams