[HN Gopher] Biologists Rethink the Logic Behind Cells' Molecular...
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Biologists Rethink the Logic Behind Cells' Molecular Signals
Author : theafh
Score : 67 points
Date : 2021-09-16 15:36 UTC (7 hours ago)
(HTM) web link (www.quantamagazine.org)
(TXT) w3m dump (www.quantamagazine.org)
| mensetmanusman wrote:
| In case you missed the photo competition, here is an amazing
| image of neurons:
| https://www.nikonsmallworld.com/galleries/2021-photomicrogra...
| popcube wrote:
| if this base on one research article, may I find in the beginning
| of article and hilight it? beautiful found! we can spend more
| time on try model subsystem of some molecular, fortunately, most
| of molecular biologist's work still do not need to change
| thanatosmin wrote:
| This is the paper the article is covering:
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5612783/
|
| It is beautiful work, but this breathless coverage really ignores
| that these properties have been previously characterized in other
| receptor signaling families like FcRs, cytokines, FGFR, TGFb,
| etc.
| zosima wrote:
| The main problem is the old idea, that the message is the
| messenger.
|
| In a way that is still true, but its not one message per
| messenger molecule. The message is intimately connected to what
| other messenger molecules are around, what are they bound too,
| what composition of receptors are on the cell surface, what are
| those receptors connected to, what secondary messages are being
| sent intracellularly and what messages have the cells received
| previously.
|
| As we have understood the hormones passing loud, clear and
| overruling messages (like e.g insulin and thyroid hormone) we
| start discovering the much more specific and context-dependent
| hormones. And those are going to have effects that are much more
| dependent on the cellular state, and so are much more difficult
| to understand.
|
| It's extremely complex, because the state of the cellular
| machinery is huge, and quite a lot of things we can't really
| observe directly.
| hirenj wrote:
| The most remarkable thing about this article is that there are
| still people surprised that the lock and key analogy has limited
| utility. I'd even argue that the new model they highlight doesn't
| even go far enough, and that a better model may involve
| promiscuous binding with receptors, coupled with mechanisms to
| amplify signals from binding events (through e.g., recruiting
| extra receptors to the place on the membrane where interaction is
| taking place)!
| hirenj wrote:
| Thinking about this a bit more, I could also imagine that cell
| state could not only be encoded in the cell proteome,
| phosphoproteome etc, but also in the set of already activated
| (primed) receptors on the cell, so that the final signal only
| gets sent in cells that have been appropriately primed.
| lurquer wrote:
| The analogies used to understand living systems always track
| technology.
|
| In the 1800's when 'fields' were the new thing, folks assumed
| cells (or, more generally, tissue) has invisible vital forces
| that dictated morphongenesis etc.
|
| With the development of steam, internal combustion, etc, living
| systems were viewed in terms of energy and chemical reactions.
|
| Then, electronics... with digital, everything -- from DNA on
| down -- was viewed as, essentially, a computer program.
|
| Now, as we're getting more comfortable with chaos and complex
| inscrutable systems (such as neural nets and the like), we view
| the mess of proteins less like a lock-key and more like a
| dynamic complex system.
|
| Not being critical... but, it's worth noting the source of
| these analogies.
| TeMPOraL wrote:
| I never liked this hypothesis. The way I see it, we're
| _returning_ to a "dynamic complex system" view from a brief
| infatuation with computing, and I'm not even really convinced
| the naive computing analogies were present anywhere else than
| in popular science and K-12 education. I'm having trouble
| imagining serious scientists believing there's a discrete,
| digital logic present in what's clearly an analog system
| built out of feedback loops - a conceptual framework that
| dates to the beginning of the 20th century if not earlier.
| VSerge wrote:
| I think (hope) that the deterministic model known as lock and key
| has been known to be a flawed view for quite some time. Books
| published in the early 00s (notably "Ni Dieu ni gene", by Kupiec
| and Sonigo) were already making this point in a popular science
| format, and explaining that even the concept of cells exchanging
| signals was flawed.
|
| A cell has no evolutionary reason to transmit signals. It will
| however eat molecules it can use, and excrete molecules that are
| no longer needed, because this allows the cell to survive and
| reproduce. A white blood cell eating a bacteria doesn't do so
| with an intention to protect some organ somewhere in the body, it
| does so like predator eats prey. Leukocytes who eat well, ie face
| a bacteria they can eat, then multiply, and end up eating all the
| bacteria, before dying off when there's nothing more to eat. So
| they protect the body and then remove themselves, not because
| they have the intention to do it for the greater good, or because
| they received a signal, but because they have evolved to prey on
| bacteria within the ecosystem of the body.
|
| Thinking of the body as a well ordered mechanism is a flawed
| view, there are no locks and keys, and most likely very few
| signals if any. Thinking of the body as a dynamically balanced
| ecosystem seems much closer to how cells behave and to the
| fantastically complex feedback systems that have evolved over
| eons and are now balancing the populations of cells in our
| bodies.
|
| We may be ecosystems of individually oblivious and dumb little
| cells, but isn't it wondrous that from this emerges a complexity
| that can say "I" and has consciousness of self?
| tines wrote:
| But reproduction is a fundamental aspect of evolution, and
| (most?) cells in the body don't reproduce on their own, but
| rather they are manufactured. T cells for example are
| manufactured by bone marrow and the thymus multiplies them if
| I'm understanding correctly. So I'm not sure how that fits in
| with the view you explained in your post.
|
| In other words the T cell doesn't get feedback on its own
| fitness. The fitness feedback is at the level of the
| reproductive success of a human being (healthy humans can have
| more kids than sick ones), not the reproductive success of a T
| cell (because it has no reproductive capabilities and therefore
| cannot be subject to selection pressures). Correct me if I'm
| wrong.
| mensetmanusman wrote:
| Humans who make incorrect T cells die, then those T cells are
| gone from the evolution chain.
| UnFleshedOne wrote:
| To support your point: there are cells that get direct
| fitness feedback. They call them cancer.
| zosima wrote:
| Obviously a damn lot of cells have an evolutionary reason to
| receive and transmit signals. Otherwise the whole body dies,
| and so do the cells.
|
| Evolution on the level of multicellular organisms happens on
| the organism level and not on the cellular level (except in
| case of cancer) and so multicellular organism cells have
| incentives to do what is best for the organism as a whole, (and
| the organism's offspring) and not for the particular cell.
|
| Hormones being passed between different parts of the body seem
| to be the way most communication happen inside the body, and
| it's definitely not in any cell's long term interest to ignore
| those signals. Even if the signal orders the cell to shrivel
| and die.
|
| The only way for the DNA in a cell of a multicellular organism
| to survive long-term, is to create an entirely new organism,
| and there is a lot of order in the body to make sure that the
| vast majority of cells that don't fall in line, are killed
| very, very fast.
| Socketier wrote:
| > Thinking of the body as a well ordered mechanism is a flawed
| view
|
| That's a bit of a leap.
|
| The order and organisation of the human body is beyond every
| technology we have ever developed to date.
|
| We discover what appears to be disorder in a healthy, non-
| aberrant system and make leaps to justify its disorder. Using
| the same philosophy that brought in the "junk dna" theory, we
| then settle the on acceptance of it being a mishmash of cobbled
| together mutations. But then as the years go on we find another
| level of order in that "chaos" and we're humbled again.
|
| >but isn't it wondrous that from this emerges a complexity that
| can say "I" and has consciousness of self?
|
| You're right, it is wonderous, and if we assumed order first, I
| suspect we'd look harder for it and find it faster than
| assuming chaos so early every time.
| fao_ wrote:
| > if we assumed order first, I suspect we'd look harder for
| it and find it faster than assuming chaos so early every
| time.
|
| But that's exactly what the field of biology (and every other
| science) has been trying to do for 2000 years. We keep coming
| up with flawed analogies for systems that are inherently
| chaotic. Chaos can follow from simple rules, which is the
| entire basis for Chaos Theory.
|
| That doesn't mean that there _aren 't rules_, it means that
| the amount of predictions we can make about the system are
| limited and that the system may arbitrarily behave
| 'erratically' or non-deterministically, which biological
| systems _often do_! (i.e. the scales that biologists and
| microbiologists are primarily looking at).
|
| The fact that there is a resulting, large-scale purpose
| emerging from it is an 'accident' of nature, in as much as
| that behaviour is not _intentional_ , it is not created with
| a will or intent for those specific effects, but pure
| causality and the evolutionary fact that systems without
| those characteristics either could not propagate in the
| environment, or could not support other systems like itself
| to propagate.
| andrei_says_ wrote:
| Fun fact, some yogic teachings see the process of
| identification as a sort of possession by entities that get to
| pilot us when we identify with them.
|
| As in - "I want X" where the I identifies w the wanting lets
| the wanting take charge.
|
| Same with recognizing oneself as an ongoing singular
| personality.
|
| ever changing identification with various things perceived as
| self.
| radicaldreamer wrote:
| Lucas' midichlorians probably came from this idea... (thank
| god we never saw those set of films!)
| asdff wrote:
| >A cell has no evolutionary reason to transmit signals.
|
| I don't think that's true. Signalling is important for
| multicellular coordination which can improve the fitness of the
| individual cell.
| hackinthebochs wrote:
| If the parent's argument were true, you wouldn't see
| apoptosis where individual cells sacrifice themselves for the
| good of the organism. There's just no way this behavior can
| be explained without signalling and selective pressures that
| favor the group over individual.
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