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Simulating a minimal cell in the browser

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Re: Simulating a minimal cell in the browser

#3
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.

Re: Simulating a minimal cell in the browser

#5
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.

Re: Simulating a minimal cell in the browser

#6

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.

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

Re: Simulating a minimal cell in the browser

#7
post #2

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.

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.

Re: Simulating a minimal cell in the browser

#8
post #3

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.

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

Re: Simulating a minimal cell in the browser

#9
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_...

Re: Simulating a minimal cell in the browser

#10
post #4

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?

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)

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