Immunity by incompatibility – hope in chiral life

[Duda Jarek]

There are programs searching for minimal cell (e.g. https://www.nature.com/articles/s41586-023-06288-x ) but for full synthesis it is not needed.

Being able to synthesize mirror ribosome and DNA/RNA, they could get all required enzymes - then enclose it into a membrane ... and why wouldn't such minimal cell work? (to be further extended with more functions)

From fig 2.4 of the report:

This is bottom-up approach, but the report also discusses top-down: trying to stepwise convert natural cell into mirror one through various approaches, e.g. genetic code reprogramming like replacing tRNA with carrying mirror amino acids.

Section 2.3 of report:

"1. Production of mirror-image proteins in vivo by creating a crossover pathway made of natural-chirality components.
2. Production of mirror-image proteins in vivo by creating an entirely mirror-image central dogma.

3. Delivery or assembly of a full mirror-image DNA genome in vivo, and removal of the natural-chirality genome, to create a mirror bacterium."

 

Edited 22 hours ago by Duda Jarek

[CharonY]

9 hours ago, Duda Jarek said:

Being able to synthesize mirror ribosome and DNA/RNA, they could get all required enzymes - then enclose it into a membrane ... and why wouldn't such minimal cell work? (to be further extended with more functions)

It simply doesn't. What we know is that the a lot of more is needed. There is a list of things folks assume is needed, but so far putting them into a membrane has not yielded a viable cells. This is why I mentioned that we need to figure out what is needed minimally first, as obviously we are still missing critical elements.

Again, what you proposed is early thinking about cells and as it turns out again and again, it does not result in viable cell. That is why with enormous financial investment at that time, the only thing folks were able to come up with was to remove DNA and then put a reduced version back into the cell it came from. The graph is basically ignoring all the critical steps. It is a bit like:

Build rocket-> develop system for FTL-> explore different star systems.

Also, while the authors acknowledge that those very theoretical organisms would need to compete with existing organisms for molecules with the more common chirality, they actually just speculate that they will somehow overcome that. This suggest that you would need to bioengineer all the contingencies into the system, which normal bacteria are able to do from the get go.

The authors are skipping a lot of steps, and from my perspective, these steps are the actual challenges.

[Duda Jarek]

Yes, they use this vague "boot" verb for kind of bringing life to a synthetic cell - but what exactly is it?

Naively there is just chemistry - statistical reactions in cytosol as a dense soup of biomolecules ... recreating composition of this soup (for some minimal cell with just central dogma), what more is needed to make it alive?

 

[CharonY]

2 minutes ago, Duda Jarek said:

Yes, they use this vague "boot" verb for kind of bringing life to a synthetic cell - but what exactly is it?

Naively there is just chemistry - statistical reactions in cytosol as a dense soup of biomolecules ... recreating composition of this soup (for some minimal cell with just central dogma), what more is needed to make it alive?

 

 

That is the exact issue/question: what is needed to make it alive? We don't know and have not been able to achieve it. It is the same as FTL- we merely have to find a way to overcome the speed of light limit. Naively, it is just bending time and space. How hard can that be?

Again, until someone actually figures out how to build a cell from scratch, we are talking hypotheticals here. Not that this might not be important at some point in the future, but in contrast to many other things that are a risk right now, it is still a hypothetical. Honestly, if we wanted to prevent us dying from infections, someone should figure out how to restore trusts in vaccinations and go from there. Mirror or not, organisms will have a 3d structure to work on.

[Duda Jarek]

While as a physicists I can say FTL is forbidden by special relativity (but in theory allowed by general relativity) ... I honestly cannot imagine obstacles for recreating cell chemistry - generally easily made outside cell ... so recreating original cytosol composition of some minimal cell, why wouldn't it work? Which chemical processes? They would work individually, but couldn't synchronize like in a living cell?

Anyway, looks like these are your words against their. Searching for "boot synthetic cell" I see lots of positive examples. Could you support your view with some references?

ps. Lots of talks from Build-a-Cell seminar (tomorrow about mirror bacteria I plan to visit): https://www.youtube.com/playlist?list=PLb2LmjoxZO-gKWXZZadcko8tHHkPuEeJT

E.g. 2020 John Glass from J. Craig Venter Institute (e.g. minimal genome: 483 kbp, 432 proteins, 39 RNAs):

 

Edited 1 hour ago by Duda Jarek

[Duda Jarek]

Just watching a week old presented by Yutetsu Kuruma from Japan Agency for Marine-Earth Science and Technology: Design and construction of artificial cells based on cell-free system - mentions the most difficult is cell replication, where I completely agree ... but just recreating (mirror) central dogma looks doable (?) - and might be sufficient for safe mass production of mirror biomolecules (?) ... or will become the first step toward replicating mirror cells ...

 

Edited 56 minutes ago by Duda Jarek