Morpheus Unbound

January 18, 2008

A year ago, Arthur Lander published a review in Cell entitled “Morpheus Unbound: Reimagining the Morphogen Gradient”. It’s an articulate review of morphogen gradients — their formation, function, and regulation. He highlights the history of morphogen study and in so doing paints a picture of both how different perspectives have enriched the field and how it has evolved over time. It is a great read, heavily recommended.

My thoughts and comments from reading Lander’s review:

  1. Diverse perspectives are important in truely understanding a problem. Theorists and experimentalist are complementary perspectives … and it took insights and input from both to begin to understand morphogens. This kind of diversity can be reached by a team of individuals or by committed individuals who are willing to be a polymath / a renaissance man / an “antedisciplinarian” [See Eddy SR (2005) “Antedisciplinary” Science. PLoS Comput Biol 1(1): e6 doi:10.1371/journal.pcbi.0010006].
  2. Bias can arise from a singular focus, but understanding comes from integrating multiple levels of focus. Here I mean a very particular kind of focus … choosing a perspective (theoretical, experimental, engineering, mathematical, modeling, etc) and then focusing on a particular level or depth of understanding (gene oriented, genome wide, intercellular, tissue). The integration of multiple different levels of focus is a systems approach. Hence Lander says, “I favor greater integration of systems biology approaches …”
  3. Complexity typically arises from trying to meet a variety of diverse (and sometimes contraditory) performance objectives. These objectives can have spatial, temporal, and evolutionary dimensions. Therefore, Lander: “we may thus hypothesize that, in every morphogen gradient system, the dynamic and regulatory mechanisms we observe are directly related to the balancing of performance objectives, among them robustness to some, but not all, perturbations.” Likely true of many things in biology besides morphogen gradients. Dobzhansky said it best, “Nothing in biology makes sense, except in the light of evolution.”
  4. Lander: “Life is dynamic on many timescales. Molecules bind and react, cells come and go, organisms are born and die, species evolve.” In short, biology is dynamics — in both temporal and spatial scales. And in biology an awful lot of spatial motion is stochastic. Random walks have interesting properties which aren’t entirely intuitive. Furthermore, when you add production and destruction, creating a gradient, things can get even stranger. Now try to understand its regulation. Clearly we need better, richer, and more spatially aware probabilistic models.

I’ll end with a quote from Lander’s 2001 bio at American Society for Cell Biology: “As Lander sees it, the major challenges now facing cell biologists lie not so much in the ability to gather data but in the ability to provide quantitative frameworks for understanding and predicting the behaviors of complex systems, such as signaling networks, gene regulation networks and macromolecular assemblies.”

LANDER, A. (2007). Morpheus Unbound: Reimagining the Morphogen Gradient. Cell, 128(2), 245-256. DOI: 10.1016/j.cell.2007.01.004

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