by surprisetalk on 6/17/25, 4:18 AM with 14 comments
by hobofan on 6/20/25, 6:13 AM
> By 2021, these engineered bacteria could be simulated in unprecedented detail. Every gene, every major protein, and nearly every metabolic reaction in JCVI-syn3A.
I think the crux is here:
> Even after years of study, 91 of JCVI-syn3A's genes remain unannotated, of which roughly one-third are essential. Deleting any single one kills the cell, yet we have no idea what they do – representing some of biology's most fundamental unsolved puzzles.
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I think minimal cells and virtual cells are especially exciting as they open up a path to create fully controlled experimental environments for biochemistry from the ground up.
Right now sooo much time in biochemistry goes into working around the limitations of what already happens to be present in an organism. E.g. we may know 5% of mechanisms that go on in a cell, but the remaining 95% percent of mechanisms that go on may still brick your experiment, and without knowing about them you essentially have to shrug and trial and error your way through them.
In contrast in a synthetic minimal cell, we could start out with an organism where we know 95% of the mechanisms that are going on, and then study new mechanisms one gene at a time, steadily building up to bigger and bigger mechanisms.
Strangely it seems to me that a lot of effort is going more into being able to simulate full cells that contain unknown mechanisms, rather than trying to use the capabilities to create hypothesis to uncover the unknown mechanisms. Yes, that probably expedites the path towards simulating much bigger human cells, but ultimately still leaves us in the dark on most fronts.
by nextos on 6/20/25, 5:15 AM
It's interesting how high-throughput perturbation assays have led to data-driven whole cell models. But these are not yet good at making robust predictions.
Probably the future are hybrid neuro-symbolic models.
by maltee on 6/20/25, 10:04 AM
by moralestapia on 6/20/25, 7:56 AM
This is exactly what I'm an expert at, I even coined a term in the field [1], :).
Since I started doing this 15 years ago (and I know the field predates me by much), one always has had this feeling that we are so close to a big breakthrough in biological simulation, but at the same time, progress has been kind of "slow". I think the reason for that is because pushing the envelope forward in this field requires mastering three (maybe four) different disciplines, your pick of [Bio, Chem, CS, Math, Physics]. Very few people reach this level of simultaneous understanding of all these pieces.
I'm not trying to gatekeep the field, though, much of the progress here (including many of the papers mentioned in TFA) is work coming from PhD students. Anyone could jump into this, but you really need to sit down and try to make sense of it for a while, years. PhD gives one the perfect opportunity for that.
Anyway, I hope this thing keeps going on forward, it's one of the ultimate goals of Biology and it would be extremely beneficial to the world.
1: https://www.frontiersin.org/journals/plant-science/articles/...