[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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       (page generated 2021-09-16 23:01 UTC)