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Mitochondria 2.0?
I've had a thought that's been eating at my brain for years and always wondered why it couldn't work. I can't write up a big thing right now (exam tomorrow) but this has been bugging me so I'd love to get your thoughts. Mitochondria ended up in the cell by being eaten basically, but the cell kept them. I read a paper a while ago about someone who infected cells with a bacteria, but in a way so they both survive. So the idea is, could you add something like mitochondria? Modify a bacteria with a property you want to not interfere with the cell and divide slowly, only as fast as is needed to keep up numbers between cycles. Give the cells a new function and whole set of proteins to make use of just by adding in a new "organelle". In theory if you did it to a germ line cell and propagated it enough you could recreate that event but also make neat cells
Thoughts?
Comments
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https://en.wikipedia.org/wiki/Symbiogenesis
Wiki page to save everyone else 3 minutes of googling.
Seems interesting.
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So, interesting thought. I know it's been done to death, but perhaps, rather than fiddling directly with the genetics of a cell, why not just incorporate a preexisting organism with bio-luminescence.Something other thoughts(I have no idea whether or not organisms exist that can do such things). Perhaps an organelle that, when exposed to ambient temperatures above a certain point, initiate an endothermic reaction until the temperature normalizes. Or perhaps one that can create a considerable amount of energy/a flame. Or perhaps an electrical charge. One phylum, Thermotogae Looked interesting. They can produce hydrogen gas, and breakdown complex carbohydrates.
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This has so much potential for both awesome things and horrendous diseases. One of the main issues I foresee is mutations - if you engineer a "useful" organelle using bacteria as the basis and make it easily get inside human cells, what happens if the "useful" functionality is mutated out and it starts dumping toxins like any traditional pathogenic bacteria? Evolution is an alien god, read this article to see why you should treat it with great respect: http://lesswrong.com/lw/l8/conjuring_an_evolution_to_serve_you/
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The issue comes down to failure rate over time as viewed by us at this point. What we are seeing is the current state after thousands of billions of failures. So how many tests do you do before you decide that the system doesnt have some issue?Beyond that, you need to remember the point that I always mention when modifying bacteria. The bacteria needs to benefit from the arrangement or it will be removed from the system. That's just how it is. Unless you are making a system that helps the bacteria (reduces metabolic load, increases reproduction chances, something) it's a burden, and they will eventually remove it.There is a sea slug that eats algae and incorporates its photosynthesis pathways into itself, but it needs to be re-upped. Might be a good place to start looking.
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That slug was what gave me the idea back in highschool. If it can take in algae and use them, even temporarily its a great start indeed. If you're going through the trouble of modifying the input bacteria then ya modify them to work with the cell so they don't lose their shit and either die or overgrow. Easiest way I figure is knock out a few metabolic pathways and let them feed on something in the cell that it easily regulated. Obviously this would take a lot of work so for the time being let's ignore how you get them to stick and focus on what a good application of this would be. Chloroplasts as discussed are useless for humans, not enough surface area. So we need a novel function that is both applicable and useful. I like the glowing idea. Although maybe aa protocell that us meant to break down after a while would be better. Then it could be set to only have what's needed. It could import material from the host cell. Build in a kill switch so if it stops working the cell gets rid of it. Would take some effort but not thhhaaaat much. But protocells can't be found in nature so bacteria may be a better start. I dunno. Thoughts?
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A question in regards to the issue of the effort required to get things to stick: Is it easier to make whatever bacteria/cell component we're putting inside our target bacteria/protocell directly "help" the target bacteria/protocell, or is it easier to "tell" or force the target cell, through various means, to keep our new trait, and then slowly adding support mechanisms that ensure that the target cell keeps the trait over time?What about something that serves as an Analog or Digital signal input(Either via light or electricity) for the cell? Perhaps something that only receives a certain amount of data, once every hour/day, and acts upon the data provided (Perhaps have a color of light for each different DNA base, and have it encode a strand of DNA based on the colors of light flashed on it. It works out conveniently, because you don't really have too many/any cases where a base bonds to another base of the same type.)
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There are a lot of relatively benign intracellular pathogens as well. Taxoplamosis is cool because it's a protozoa, it's in something like 50 percent of the global population, and for the most part symptomless. The bacteria responsible for q fever is possible. It does done bad bad shit, but only in about 50% of people. There are even some intracellular fungi, but no appropriate ones come to mind. The relationship between mitochondria and the nucleus of a cell is pretty complex though. The majority of the DNA for mitochondrial proteins is in the nucleus of the cell I believe and not actually from the mDNA.
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If we started with something like that and worked up it would certainly be easier. And less dangerous to work with just in general. So lets start there. Bacteria that already are intracellular but not really pathogenic. Find a good one and we can add a function. and then we go from there.
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Yeah, there's crazy amounts of over lap, so even thought you have a situation where all of your mDNA comes from your mom, it's still so intertwined that it's not like you can just slap stuff in or say something is separate. There's those thousands of ages of evolution that make things so tangled.
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Right so start with it seperate and go from there. Doesn't need to be a perfect thing off the top, lets just get something to build from
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So, making a bacteria glow without modifying the bacteria itself to express "glow-proteins". That sounds like a nice place to start.
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Except review what glims said. If the modification isn't beneficial, then it's a metabolic strain. In a few generations or even 100 generations.. no more modification.
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Yes, I'm aware. As I said, we can worry about that bit after. First lets find a good host and a trait we want expressed. We can figure out how to make it stick after. Cart and horse as it were.
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Also modifying the bacteria is totally still gonna be needed. Glowing is the easiest thing we could do if we went with GFP. But i'd ideally like something a little more interesting.
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Myostatin Inhibition. One should choose a bacteria as they are far easier to work with than something like Taxo. Also, an optimal choice would be susceptible to a particular antibiotic.
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So, where should we start in terms of bacteria? I know E. coli is used for a lot of lab work, but endotoxins can be a problem.
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Well the start is having mammalian cells cultured. Then you use an intracellular obligate type of bacteria. You need to probably introduce the desired gene into the bacteria in the form of plasmids. Of you can't purchase a plasmids you need to make em. Since we are probably talking about a mammalian gene. Your probably going to make cdna. You need a triggering scheme or perhaps a way to keep the gene being expressed. Sorry asleep still
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So the cDNA is the plasmid for the bacteria? Also, would it be better to start with a non-pathogenic bacteria (I've found only one so far) or start with a pathogenic strain and engineer the pathogenic tendency out? And in your experience @glims and @cassox , what's the most effective way to keep the gene expressed?
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Start with the non pathogenic bacteria. The thing is that most of our gene tools come from bacteria. Your standard grade bacteria will out edit your work any day. So not only do you need the non pathogenic type, but you need the special tweaked ecoli that have basically been neutered. It's a go to.Linking your favourite gene (yfg) to an antibiotic resistance is the standard method to for maintaining expression in bacteria. Thus you link yfg to the antibiotic, you culture them in the antibiotic, they keep yfg cause losing it means losing their resistance, and death.Maintaining expression in mammalian cells is a completely other thing and not worth diving into now until initial steps are made.The take home issue is still making a system that the bacteria benefit from. Using antibiotics to constantly pressure a system will still end up with and product down the road that has all the benefits that they want and nothing that you care about.
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If going this route, consider using an Aminoglycoside antibiotic. It's one of the few types that function intracellularly. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90216/
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What about the cDNA? And would Mycobacterium Hiberniae be a good choice as an alternative to E. Coli? It's non-pathogenic and from a genus that possesses intracellular obligate bacteria, though I'm not certain if it possesses those traits too.
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I'm going to say um maybe. I mean, we're talking about tried and true techniques that work fairly well. I'm not sure why you would want to use something just cause it sounds neat (maybe im misunderstanding). Plasmid work is basically engineering at this point. If you have solid evidence that the tools you want to use are better for this project, then sure. Otherwise, use the thing that works.
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Crazy thought:Would it be possible to engineer chloroplasts to function inside of animal cells?
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yes. would be worthless though. As has been discussed at length, we don't have enough surface area for it to be worth it in humans.
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Found this paper on artificial endosymbiosis. It's mostly an exploratory review and they don't actually attempt it but they lay out some background really nicely. LINKThe point they make is for this to work you need to store some of the genes for the endosymbiot of choice in the host organism. Seemingly the more this happens the better the connection and the longer it will last. There must be some tipping point or some way to make it permanent but it'll require more research.
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