[HN Gopher] Simulating a minimal cell in the browser
       ___________________________________________________________________
        
       Simulating a minimal cell in the browser
        
       Author : agnosis
       Score  : 96 points
       Date   : 2024-01-20 10:22 UTC (12 hours ago)
        
 (HTM) web link (technistuff.com)
 (TXT) w3m dump (technistuff.com)
        
       | agnosis wrote:
       | Have you ever wondered how life's most basic units, cells,
       | operate? As a programmer and cell biology enthusiast, I embarked
       | on a journey to simulate the simplest cell using TypeScript.
        
         | ClaraForm wrote:
         | In biology, there's a whole field of research dedicated to
         | minimizing cells and their complexity. If you message "John
         | Glass" he might be interested in having you model his work!
         | 
         | Edit: oops you've already modeled John's work! That's awesome.
         | :D I've attended a few talks by John and I think he'd still be
         | interested in seeing whether the modeling side of things can
         | explain why he can't get the minimal cell smaller.
        
       | mtekman wrote:
       | This is really amazing. I wonder if confounders such as
       | transcriptional bursting[1] are modelled too? I did not check but
       | I assume cell-cycle is readily modelled.
       | 
       | 1: The tendency of a single cell to perform transcription in
       | bursts of activity/inactivity, which averages in bulk tissue as a
       | continuous variable.
        
         | bglazer wrote:
         | They use a master equation for transcription, so they could
         | theoretically get bursty behavior. But, my understanding is
         | that the most well understood cause of burstiness is caused in
         | eukaryotic cells by rearrangement of histones allowing
         | transcription. Since this happens on a slower timescale than
         | transcription you get bursts when the histones periodically get
         | out of the way.
         | 
         | Bacteria (like this minimal cell) don't have histones but they
         | do have bursty transcription, which is weird. Apparently it
         | might be caused by DNA supercoiling and uncoiling [1], which is
         | weird and cool. That said, they definitely don't model that, so
         | I'd be surprised if they got bursting transcription. If they
         | did, I'd be interested in knowing what mechanism is causing the
         | transcription bursts in the model.
         | 
         | 1. https://www.cell.com/cell/pdf/S0092-8674(14)00739-9.pdf
        
       | 331c8c71 wrote:
       | Fascinating stuff, thanks! A recent workshop with recorded talks
       | on such cells https://www.jcvi.org/events/minimal-cell-workshop
       | 
       | I am wondering if other researchers can procure or produce these
       | cells or these are rather a know-how of JCVI?
        
         | koeng wrote:
         | I gave a talk at that workshop! (I'm making the 61 codon
         | version of JCVI-Syn3a)
         | 
         | You can get the cells as a researcher, but basically forget
         | about it for a commercial user or hobbyist. They're also
         | annoying as hell to grow. I'm trying to synthesize it from
         | scratch for the precise reason of freeing it from MTAs
         | (material transfer agreements)
        
           | DylanSp wrote:
           | Sounds like you're doing good work! Out of curiosity, can you
           | give a layman's explanation of what makes them hard to grow?
        
             | koeng wrote:
             | Their media is real complicated and expensive (plus
             | difficult to prepare: can't just throw everything in an
             | autoclave), and they don't grow very fast, and they don't
             | grow to a high concentration. Basically that means that you
             | can easily get contamination (like you would growing human
             | cells), and even when you do get growth, it's dilute.
        
       | gus_massa wrote:
       | Does this model have operons like
       | https://en.wikipedia.org/wiki/Lac_operon [1] ? I guess they are
       | skipped to reduce the complexity of the model.
       | 
       | [1] This operon was the first that was discovered, the idea is
       | that the cell produce the enzymes to eat lactose only if there is
       | lactose and there is no glucose.
        
         | agnosis wrote:
         | At the moment it does not. As per the paper[1]:
         | 
         | > We do not simulate any operonal structures for protein-coding
         | genes and transcribe each gene individually. Once
         | transcriptomics data becomes available for Syn3A to determine
         | operonal structures, we can incorporate transcription of
         | operons into this model.
         | 
         | [1] https://www.cell.com/cell/fulltext/S0092-8674(21)01488-4
        
       | koeng wrote:
       | We don't even know what like, 20% of the genes do. Simulations
       | are neat, but they miss a lot of underlying biology that actually
       | makes an impact on engineering.
       | 
       | One of my favorite papers was published 40 years ago on this
       | topic https://pitp.ias.edu/sites/pitp/files/morowitz-
       | completeness_...
        
         | hobofan wrote:
         | If you read the article you'd know that that's exactly why
         | organisms such as JCVI-syn3A were created, where we know the
         | (or at least some) function of 80% of the genes.
        
           | bee_rider wrote:
           | Oh wow, a RISC (reduced instruction set cell).
        
           | koeng wrote:
           | I'm well aware. I was in charge of designing and synthesizing
           | the entire gene set, optimized for E.coli, in order for
           | scientists to easily try to discover the function of these
           | genes https://stanford.freegenes.org/collections/gene-
           | sets/product...
           | 
           | Out of the 100 or so unknown genes we had/have, only like 3
           | unknowns were actually used for research. Such is science
           | sometimes.
        
         | ramraj07 wrote:
         | I thought you posted "Can a biologist fix a radio?" It's also
         | very pertinent to this topic:
         | 
         | https://www.cell.com/cancer-cell/pdf/S1535-6108(02)00133-2.p...
        
       | DylanSp wrote:
       | Interesting blog post, based on an interesting paper.
       | 
       | For a bit more background, there's been a couple of posts on the
       | "minimal cell" concept on Derek Lowe's venerable In the Pipeline
       | blog. This 2016 post [1] talks about the initial development of
       | the JCVI-syn3.0 cell; this 2023 post [2] goes over a paper that
       | studied the evolutionary dynamics of these minimal cells.
       | 
       | [1] https://www.science.org/content/blog-post/smallest-viable-
       | ge...
       | 
       | [2] https://www.science.org/content/blog-post/ground
        
       ___________________________________________________________________
       (page generated 2024-01-20 23:00 UTC)