Chiral life concept - creating mirror image synthetic life?

[jarekd]

Imagine mirror image of a cell - built from a scratch using mirror images (enantiomers) of molecules of the original cell. It should work as standard one, but use e.g. L-sugars instead of our D-sugars: article.

Some possible applications:
- doubling the space of possible enzymes we could design and produce,
- such organisms would be incompatible with standard pathogens - we could design bottom-up really sterile ecosystems for extreme conditions like Mars,
- maybe chiral humans immune to our pathogens - which are direct or indirect cause of most of illnesses including cancer - here is a long list of human diseases associated with infectious pathogens,
- ... ?

There are announcements of creating synthetic ribosome, cell membrane ... synthetic cell, so maybe within a few decades we could synthesize the whole alternative version of life - even manually using allowing to control single molecules AFM/STM synthesize chiral RNA, ribosome ... use it to produce proteins, which would be finally pumped into liposome to create first chiral prokaryote.
Eucaryotes are much more complex so probable will take a few decades more, but we could target cell division phases when their structure is simplified, we could create organelles separately ... or even use a molecular 3D printer (AFM/STM) to build frozen parts molecule by molecule ... then creating chiral humans will be just inevitable.

What do you think of such possibility - is it possible to realize? how much time will it take? what other applications could you think of? what would be implications to our society? ...
And generally: what realistic practical applications of synthetic life could you think of?

 

[Superposed_Cat]

Interesting...certain enantiomers are deadly to standard lifeforms but if the whole lifeform was mirrored...

 

[jarekduda]

I have restored the Wikipedia article - please help improving it:
https://en.wikipedia.org/wiki/Chiral_life_concept

 

[jarekduda]

It turns out it is already starting - synthesized mirror image version of polymerase in 2016 and plans to synthesize a cell:
http://www.nature.com/news/mirror-image-enzyme-copies-looking-glass-dna-1.19918

Remember that there are also dangers - for example mirror-chiral photosynthesizing cyanobacteria could dominate our ecosystem as not having natural enemies, disturbing the food chain: producing L-sugars instead of our D-sugars.

 

[jarekduda]

Good 2010 WIRED article: "Mirror-Image Cells Could Transform Science — or Kill Us All"
https://www.wired.com/2010/11/ff_mirrorlife/

The "Kill Us All" part is for example about this mirror-cyanobacteria ... which might be synthesized e.g. in some Chinese lab in 10-20 years (like this mirror polymeraze from 2016 Nature article) - the article gives Earth's life a few centuries left in such case:

"It gets worse: If mirror cells acquired the ability to photosynthesize, we’d be screwed. “I suspect that all hell would break loose,” says Jim Kasting, a climate scientist at Penn State University and an expert on the global carbon cycle. (He is also Jerry Kasting’s chiral twin brother; Jim is right-handed, Jerry is left.) All it would take would be a droplet of mirror cyanobacteria squirted into the ocean. Cyanobacteria are at the base of the ocean’s food pyramid, converting sunlight and carbon dioxide into more of themselves. After doing some rough calculations on the effects of a mirror cyanobacteria invasion, Jim Kasting isn’t sure which would kill us first—the global famine or the ice age. “It would quickly consume all the available nutrients,” he says. “This would leave fewer or perhaps no nutrients for normal organisms.” That would wipe out the global ocean ecology and starve a significant portion of the human population. As the CO2 in the ocean was incorporated into inedible mirror cells, they would “draw down” CO2 from the atmosphere, Kasting says. For a decade or two, you would have a cure for global warming. But Kasting predicts that in about 300 years the bugs would suck down half of Earth’s atmospheric CO2. Photosynthesis of most land plants would fail. “All agricultural crops other than corn and sugar cane would die,” he says. (They do photosynthesis a little differently.) “People might be able to subsist for a few hundred years, but things would be getting pretty grim much more quickly than that.” After 600 years, we’d be in the midst of a global ice age. It would be a total evolutionary reboot—both Kasting and Church think mirror predators would evolve, but whatever life existed on Earth by that point wouldn’t include us."

Would mirror cyanobacteria indeed be such dangerous?
How many years humanity needs to make its synthesis technologically available?

 

[BillTre]

He is also Jerry Kasting’s chiral twin brother; Jim is right-handed, Jerry is left.

A chiral twin would probably be something more like situs inversus, where the internal organs are reversed.
This bodily handedness has been observed at the single cell level in individually identifiable bilateral neurons which cross at the midline. One side usually crosses dorsal to the other.
Bodily handedness is set-up during embryogenesis and there are mutations that can reverse it.

Handedness differences are sometimes associated with right-left differences in brain structure, but not always.
As I recall, it is not well coordinated with brain side dominance (speech localization etc.).

 

[jarekduda]

Yes, indeed building an organism from mirror-images of molecules (enantiomers) would probably also lead to such symmetry in all scales, including heart more likely to be on the right side ... but also biological mental preferences, like specializations of hemispheres or handedness - assuming it is not cultural.
Interesting question - does this symmetry breaking require broken symmetry on the level of zygote? If not, how this left-side heart preference is biologically realized?

The most important differences for e.g. chiral human would be on the molecular level - starting with completely different smells and tastes of many substances: http://www.chemikinternational.com/wp-content/uploads/2014/02/2_14_1.pdf
Surprisingly, L-glucose has turned out tasting like the standard one, not being metabolized: https://en.wikipedia.org/wiki/L-Glucose
However, our food would probably be poisonous for such chiral human (?)

 

[BillTre]

Interesting question - does this symmetry breaking require broken symmetry on the level of zygote? If not, how this left-side heart preference is biologically realized?

It is set-up during gastrulation (after fertilization, after blastula formation (just making an initial bunch of cells)).
Gastrulation results the three primary embryonic tissues layers (endoderm, mesoderm, and ectoderm).

The normal bodily handedness involves (at least in mammals) cilia function and two TGF-β related proteins Nodal and Lefty (at least in zebrafish) being expressed in the mesoderm soon after it is first formed in gastrulation. The cilia may have to due with diffusing or sensing signaling molecules.

 

[jarekduda]

It is set-up during gastrulation (...)

So you are saying that while blastula looks to be a symmetric collection of cells, gastrula is clearly an asymmetric alignment.
However, there is needed some anchor for this macroscopic asymmetry leading e.g. to heart on the left side - a perfectly symmetric system should remain symmetric, or break symmetry in a completely random way - leading to 50:50 probability distribution for heart-sidedness.

And blastula is not perfectly symmetric - e.g. there is asymmetry on molecular level (chirality).
The question is if it can be amplified to macroscopic level? Through structure asymmetry like type of rotation of DNA helix.
Or maybe this macroscopic asymmetry is already written is asymmetry of e.g. organelle alignment of zygote?
The last possibility is that this asymmetry (preferring e.g. heart on left side) is "written" in the environment (womb), but this is the least likely explanation as the gastrulation seems to be done in macroscopically symmetric liquid.

To test the last hypothesis, mother-child correlation of dextrocardia (heart on right side) might bring a clue ... but not exactly conclusive - such correlation could be also through organelle alignment of zygote.
I would rather bet on molecular reason - that asymmetry of building blocks is amplified to asymmetry of structures they build (proteins, DNA, cytoskeleton ...), which somehow leads to asymmetry of cell alignment of gastrula ... what leads to domination of e.g. heart on the left side.

 

[BillTre]

So you are saying that while blastula looks to be a symmetric collection of cells, gastrula is clearly an asymmetric alignment.

The blastula (of zebrafish, which I am most aware of) is at first appearance, like a a symmetric pile of cells on top of the much larger yoke cell. Not all embryos have a large yolk to deal with but they are basically similar. The blastula cells have an asymmetry (non-radial symmetry) in that there are molecules indicative of dorsal vs. ventral. This has to do with an animal vs. vegetal difference in the developing embryo (animal is more ectoderm/mesoderm after gastrulation, vegetal is more endodermal). It also has to due with where gastrulation will start. They are as far as I know symmetrical around the longitudinal (anterior/posterior) axis, meaning they are right-left symmetric as far as known.

However, there is needed some anchor for this macroscopic asymmetry leading e.g. to heart on the left side - a perfectly symmetric system should remain symmetric, or break symmetry in a completely random way - leading to 50:50 probability distribution for heart-sidedness.

While this makes sense, I don't know of an observed mechanism that underlies this choice. However, I am not all that current in this research.
If I were more intrigued by this (maybe yo want to do this), I would search google scholar for zebrafish research papers showing upstream influences on the lateralized gene expression described in my previous post.
Seems likely its generated just as the cells undergo gastrulation.

The zebrafish is probably the embryo in which this could be most easily found and observed. It is optically clear at these stages, fertilized externally and develops well in a dish under a microscope, and has well worked out genetics and molecular biology techniques. Mouse, chicken, and frog embryos all lack one or more of these features.

The last possibility is that this asymmetry (preferring e.g. heart on left side) is "written" in the environment (womb), but this is the least likely explanation as the gastrulation seems to be done in macroscopically symmetric liquid.

This is certainly a possibility for mammals, but not for zebrafish or frogs, however it not clear to me how two different sets of determinants could be localized to always establish a heart on the left side laterality.
Eggs of many species are know to get loaded up with materials that can act as localized triggers for later events that come from the mother when the eggs are made. They can effect the animal/vegetal differences as well as be determinants for germ cells (which make eggs and sperm). These mechanisms put things in a particular location in the egg usually to get gastrulation oriented. The germ cells migrate so precise localization is probably not that important.
Some frog embryos have determinants like this that are responsive to how they lie in a gravitational field. If the embryos are tipped at the right time their gastrulation came be messed up, which can result in a doubled or split axis. This would make twins on a single yolk or a branched embryo with two heads and one trunk.

Interestingly, identical twins (human I think) can (but don't have to) have one situs inversus and one normal embryo. Identical twins develop from a single fertilized egg which for some reason gets divided into two independent embryos at an early stage of development.

such correlation could be also through organelle alignment of zygote.

Since cilia (an organelle made largely of microtubules and membrane) are involved in the process, they would make a reasonable candidate for causing this effect. It is possible that their structure and/or movement could be enough to initially set-up an asymmetry in a diffusing signaling molecule (or of the sensing of it by responding cells) through their movement or effects on the movement of diffusing signalling molecules) which could lead to the embryos asymmetry.
This is another thing I am not current on, but may be known.

 

[Ygggdrasil]

And blastula is not perfectly symmetric - e.g. there is asymmetry on molecular level (chirality).
The question is if it can be amplified to macroscopic level? Through structure asymmetry like type of rotation of DNA helix.
Or maybe this macroscopic asymmetry is already written is asymmetry of e.g. organelle alignment of zygote?
The last possibility is that this asymmetry (preferring e.g. heart on left side) is "written" in the environment (womb), but this is the least likely explanation as the gastrulation seems to be done in macroscopically symmetric liquid.

I am not a developmental biologist, but as I learned it, molecular chirality is translated to organismal chirality through the action of cillia. The protein components (which are chiral) that drive the motion of cilia in the developing embryo cause the cilia to rotate in a clockwise direction. This clockwise motion of the cilia is thought to define the left/right axis of the developing embryo. The mechanisms are unclear, but this may be due to cells sensing the the asymmetric flow of growth factors (morphogens) driven by the motion of the cilia or by cells directly sensing the asymmetric fluid flows.

For more information, see: http://rsob.royalsocietypublishing.org/content/3/5/130052