Each year, Sanford-Burnham’s annual symposium features a different topic. Past years have focused on infectious diseases, RNA biology and other disciplines. This year, however, the 33rd annual meeting introduced an entirely new scientific field: Structural Systems Biology.The June 7 symposium was opened with a welcome from Dr. Adam Godzik, director of Sanford-Burnham’s Bioinformatics and Systems Biology Program and one of the meeting’s co-organizers. “When I tell people I am a biologist, they think of organisms,” he said, showing a picture of zoo animals and wildflowers. “But I actually work on the parts.” With that, he flipped to cartoons of genes and proteins.
Structural Biology generates data related to the physical shape of these individual proteins– how they’re folded, how they form complexes with other proteins, what they look like in 3D. That information helps answer questions about how proteins perform their duties –facilitate chemical reactions, carry molecular signals in and out of cells, control cellular movements, etc. Understanding a protein’s structure and function helps identify its role in human health and disease, as well as its potential as a therapeutic target.
But, as Dr. Godzik went on to explain, these individual components all exist as part of a system. They are each a “node” in a network that controls an aspect of cellular behavior – turning genes on and off, communicating with other cells, metabolizing nutrients or performing any number of other processes. Systems Biology focuses on all these components and the interactions among them. Scientists in this field aim to create meaningful models capable of quantifying and predicting these complex cellular processes.
Why Structural Systems Biology?
“Each node in a system has a 3D structure that we need to understand in order to understand the whole network,” Dr. Godzik said. “On the other hand, we might not be able to understand an individual node’s function without understanding the whole network around it.”
To introduce Structural Systems Biology, Dr. Godzik and his colleagues, Drs. Dorit Hanein, Andrei Osterman, and Niels Volkmann, brought together eight speakers – outstanding leaders in both Structural Biology and Systems Biology – to explore the synergy between these fields. More than 300 scientists attended Sanford-Burnham’s annual symposium. Their hope is that Structural Systems Biology will help us better understand many human diseases.
Structural Systems Biology Symposium: the science
Sir John Walker, director of the Medical Research Council’s Mitochondrial Biology Unit at the University of Cambridge, was the symposium’s keynote speaker. Dr. Walker shared the 1997 Nobel Prize in Chemistry for his work unraveling how enzymes generate ATP, the energy currency cells cash in to do the work they need to do. At the symposium, Dr. Walker talked about mitochondria, the parts of the cell where ATP-generating chemical reactions take place. His current work – determining the structures of energy-generating enzymatic complexes in mitochondria – stands to benefit greatly from a closer link between structural and systems biology. Not only will this information create a better understanding of evolution, mitochondria are also increasingly recognized for their role in a number of human diseases, including Alzheimer’s disease, obesity, cardiovascular disease and perhaps even autism. Dr. Walker expressed his hope that this work will help identify the underlying causes of these diseases and allow scientists to design rational strategies to prevent and treat them.
The speakers that followed shared structural and systems insights on caspases (enzymes that control cellular suicide), the nuclear pore complex (the cell’s gateway between the nucleus and the cytoplasm), the human gut microbiome (the sum of all the symbiotic bacteria living in our intestinal tracts) and more. They also featured various tools they’ve created to collect, manipulate and crunch all this data. Examples include Dr. Andrej Sali’s Integrative Modeling Platform (IMP), Dr. Jim Wells’ Single Nick In Proteome (SNIPer) and Dr. Peer Bork’s My Microbes site.
“I love the title of this symposium – Structural Systems Biology. That’s really where I’d like to be, scientifically speaking,” said speaker Dr. Sali, who directs the California Institute for Quantitative Biosciences (QB3) at UC San Francisco.
Structural Systems Biology Symposium: the discussion
The symposium ended with a panel discussion that evolved into an entertaining philosophical discussion, full of what the speakers called “random thoughts.” Dr. Andrew Viterbi opened the dialogue with a comparison of biological and electrical systems. Dr. Viterbi invented the Viterbi Algorithm and a code division multiple access (CDMA) standard, both used in essentially every cell phone. He was also one of Qualcomm’s co-founders.
“Physical networks are often in flux, much like biological networks,” he said. “The best example is the mobile network. Cell phones go from various nodes to an access point, a base station. They were originally designed according to population centers, but those centers can change rapidly and dramatically. When you have a sporting event in a stadium, for example, you suddenly have a hundred thousand people in a place that they weren’t in before. So the mobile network has to be very flexible.”
A point that was repeated again and again was the need for improved technology to enhance this emerging field – better imaging techniques, computer platforms that can synthesize huge amounts of data, clever animation capabilities and more.
As speaker Dr. Art Olson, director of the Molecular Graphics Laboratory at The Scripps Research Institute, put it during the panel discussion, “Things embody knowledge. We learn something, we embody it in an instrument, then use that to generate more knowledge. These two things can’t exist without each other. The more complex the things we’re studying, the more technology we need.”