Theodicy: how cells really work, organized chaos (Introduction)

by David Turell , Thursday, September 16, 2021, 19:41 (951 days ago) @ David Turell

The latest cellular research:

https://www.quantamagazine.org/biologists-rethink-the-logic-behind-cells-molecular-sign...

"Recently, by looking closely at the protein interactions within one key developmental pathway that shapes the embryos of humans and other complex animals, Elowitz and his co-workers have caught a glimpse of what the logic of complex life is really like. This pathway is a riot of molecular promiscuity that would make a libertine blush, where the component molecules can unite in many different combinations. It might seem futile to hope that this chaotic dance could convey any coherent signal to direct the fate of a cell. Yet this sort of helter-skelter coupling among biomolecules may be the norm, not some weird exception. In fact, it may be why multicellular life works at all.

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"Yet this apparent chaos of interacting components is really a sophisticated signal-processing system that can extract information reliably and efficiently from complicated cocktails of signaling molecules. “Understanding cells’ natural combinatorial language could allow us to control [them] with much greater specificity than we have now,” he said. (my bold)

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"What Elowitz and others are now bringing to light is how BMPs pull off this trick of being so mercurial while also behaving predictably enough for organisms to stake their lives on them. These qualities seem to emerge from the layers upon layers of complexity in the composition of the BMP system, and the flexible, variable affinities of those elements for one another. Paradoxically, the complexity makes the system both more precise and more reliable.

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"It’s not simply the case, however, that each BMP dimer has designated receptors to which it binds like a lock and key. In fact, these molecules aren’t terribly choosy: Each BMP dimer may stick to several different pairs of receptor subunits with varying degrees of avidity. It’s a combinatorial system, in which the components can be assembled in many ways: less like locks and keys, more like Lego bricks.

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"The possible permutations are exhausting to contemplate. How can the BMP pathway ever deliver a specific directive to guide a cell’s fate? With so much complexity, “it took a little unconventional thought to approach the problem,” said James Linton, a research scientist in Elowitz’s group.

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"The interactions, although promiscuous, were far from “anything goes.” Certain BMPs had nearly interchangeable effects, but others did not. In some cases, one BMP plus two receptor subunits worked as well as an assembly of three different components. An assembly might work as well with one BMP swapped for another, but only if the receptor stayed the same. Sometimes two swapped components had independent effects, and their combined effect was a simple sum. Sometimes the effects mutually reinforced one another or canceled each other out.

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“Our working hypothesis is that these ligand-receptor combinations have the potential to be more cell-type-specific than individual molecules,” said Elowitz.

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:A pathway involving the family of proteins called Wnt, for example, often seems to operate alongside BMP signaling. “If you find BMP at work somewhere, it’s very likely that you’ll find Wnt,” Linton said. Sometimes the pathways are mutually antagonistic and sometimes they enhance each other. If the Wnt pathway follows similar combinatorial rules — a possibility that still needs to be explored experimentally, Elowitz stresses — then BMP and Wnt might help to refine each other’s signaling.

"Elowitz and his colleagues think that in this way, these kinds of combinatorial rules could represent a widespread “design principle” of the molecular wiring of cells.

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“'Given that promiscuity did not have to exist, but is ubiquitous, the simplest and most reasonable assumption is that it is providing some functional capability,” Elowitz said.

"He thinks that capability is, at root, information processing. “Just as neurons wired together through axons and dendrites can perform complex information processing, so too can proteins wired together through biochemical interactions,” he said. It’s an insight that other scientists have also drawn from their studies of biochemical networks. (my bold)

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"Heidi Klumpe, a member of Elowitz’s group said, “We think the cells are doing a more complex computation than previously thought.'”

Comment: if life works on organized chaos as it now seems, no wonder mistakes happen. This is the only system of life we know, and perhaps the only one that can work that God could create. And note information is processed. Massive article hard to edit. Read it all for full comprehension.