RESEARCH:
The Ferrell lab studies signal transduction and cell cycle regulation, mainly focusing the spatial and temporal regulation of mitotic entry and exit. A good deal is known already about the individual proteins that regulate these processes, which allows us now to begin to explore how these proteins work together in circuits, generating reliable systems-level behaviors.
Much of our work makes use of Xenopus laevis oocytes, eggs, embryos, and extracts, which provide a wealth of advantages for quantitative studies of cell cycle regulation. We also make use of mammalian cell lines, which have their own advantages, including the fact that they are less amphibian than frog cells.
Here we have collected some information in FAQ format about the lab's past and present research. You can skip to the page you are most interested in by clicking one of these links:
Cell fate, biochemical switches, and Xenopus oocyte maturation
Or you can just start here, with a discussion of what we think systems biology is. The following is adapted from a paper published in the Journal of Biology in 2009.
WHAT IS SYSTEMS BIOLOGY?
Systems biology is the study of complex gene networks, protein networks, metabolic networks and so on. One goal, perhaps the main goal, is to understand the design principles of living systems.
How complex are the systems that systems biologists study?
That depends. Some people focus on networks at the ‘omics’-scale: whole genomes, proteomes, or metabolomes. These systems can be represented by graphs with thousands of nodes and edges, like the hairball shown on the right (courtesy of Marc Vidal). Others, including our group, tend to focus on small subcircuits of the network – say a circuit composed of a handful of proteins that functions as an amplifier, a switch, a pulse generator, an oscillator, or a logic gate. Typically, the graphs of these systems possess fewer than a dozen (or so) nodes. Both the large-scale and smallscale approaches have been fruitful.
Why is systems biology important?
Stas Shvartsman at Princeton tells a story that provides a good answer to this question. He likens biology’s current status to that of planetary astronomy in the pre-Keplerian era. For millennia people had watched planets wander through the nighttime sky. They named them, gave them symbols, and charted their complicated comings and goings. This era of descriptive planetary astronomy culminated in Tycho Brahe’s careful quantitative studies of planetary motion at the end of the 16th century. At this point planetary motion had been described but not understood.
Then came Johannes Kepler, who came up with simple theories (elliptical heliocentric orbits; equal areas in equal times) that empirically accounted for Brahe’s data. Fifty years later, Newton’s law of universal gravitation provided a further abstraction and simplification, with Kepler’s laws following as simple consequences. At that point one could argue that the motions of the planets were understood.
Systems biology begins with complex biological phenomena and aims to provide a simpler and more abstract framework that explains why these events occur the way they do. Systems biology can be carried out in a ‘Keplerian’ fashion – look for correlations and empirical relationships that account for data – but the ultimate hope is to arrive at a ‘Newtonian’ understanding of the simple principles that give rise to the complicated behaviors of complex biological systems.
Note that Kepler postulated other less enduring mathematical models of planetary dynamics. His Mysterium Cosmographicum showed that if you nest spheres and Platonic polyhedra in the right order (sphere-octahedron-sphere-icosahedron-sphere-dodecahedron- sphere-tetrahedron-sphere-cube-sphere), the sizes of the spheres correspond to the relative sizes of the first six planets’ orbits. This simple, abstract way of accounting for empirical data was probably just a happy coincidence. Happy coincidences are a potential danger in systems biology as well.
Is systems biology the antithesis of reductionism?
In a limited sense, yes. Some emergent properties disappear when you reduce a system to its individual components. It takes a circuit, not a single protein or gene, to function as an oscillator, a switch, or an amplifier. As Linus Pauling put it, "life is a relationship among molecules and not a property of any molecule."
That said, systems biology stands to gain a lot from reductionism, and in this sense systems biology is anything but the antithesis of reductionism. Just as you can build up to an understanding of complex digital circuits by studying individual electronic components, then modular logic gates, and then higher-order combinations of gates, one may well be able to achieve an understanding of complex biological systems by studying proteins and genes, then motifs, and then higher-order combinations of motifs.
In high school I hated physics and math, but I loved biology. Should I go into systems biology?
No.
