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I'm completely in the dark when it comes to hard biotech, but have heard this labelled as a CRISPR-level development. Based off this tweet[0] from one of the p

I'm completely in the dark when it comes to hard biotech, but have heard this labelled as a CRISPR-level development. Based off this tweet[0] from one of the paper's authors. Can anyone here confirm or deny this? [0]: https://twitter.com/BanfieldJill/status/1414647658786922496 https://twitter.com/BanfieldJill/status/1414647658786922496

echelon 5y ago
They found a bacteria with extra-genomic material that isn't in the shape of a plasmid (circular DNA that is a feature of bacterial transfection and gene transfer). They believe it came from archean rather than bacterial sources. (Not really related, but many of our genes, and indeed one of our critical organelles, are also archea-derived, ie. the mitochondria.) The genomic payload is large and comes with replication machinery (it might be a useful tool!) Plasmids hold a much smaller payload than these units, and they're difficult to work with. Borgs are huge. If we can turn them into transfection toolkits, we can do larger scale genomic experiments much faster. That's extremely exciting. Much of biochemistry research and understanding is done in bacteria. They're extremely useful little computers. We just discovered an extremely useful way to hack them. In the wild, the gene payload codes for novel methane metabolic pathways. This also is of great interest. Not only for applicability to climate science, but also the natural ability to swap out or augment bacterial metabolism. Imagine all of the novel things you might swap in instead. Who knows. These might wind up in eukaryotic cells too!
- deleted 5y ago
  [deleted]
- dnautics 5y ago
  Noncircular extragenomic dna in bacteria isn't a new thing, for example, the marine algae cyanothece has linear DNA, and iirc it is important in regulating day/night cycles for nitrogen fixation (which is oxygen sensitive)
- jkhdigital 5y ago
  Wild stuff. Here's my current mental analogical model: bacterium : animal :: computer : botnet
  - canadianfella 5y ago
    What do you mean?
    - echelon 5y ago
      You can often tell someone's age by whether or not they know analogies in this format. It used to be a staple of standardized testing on logical deduction. A : B :: C : D Is read as A is to B as C is to D. The reader is meant to understand the relationship between A and B and how it's similar to the relationship between C and D. An easy one might be, basketball : hoop :: hockey puck : net But they can get quite challenging. And with multiple choice answers present in standardized testing, you often have to understand the complex relationships between many abstract concepts, and evaluate that the abstractions are of a similar type or degree. They're actually kind of fun. Here's an example taken from [1] (the source also has excellent discussion as to why they were removed) : PALTRY : SIGNIFICANCE :: A. redundant : discussion B. austere : landscape C. opulent : wealth D. oblique : familiarity E. banal : originality Pick the correct answer A-E. [1] https://blog.prepscholar.com/sat-analogies-and-comparisons-why-removed-what-replaced-them https://blog.prepscholar.com/sat-analogies-and-comparisons-w...
      - drdeca 5y ago
        Is this an age thing? I’ve been surprised a number of times by people not being familiar with this format, but they were only a year or 2 younger than me. (I’m 25) It’s a nice format for thinking about things, so if people stopped learning it, that seems unfortunate to me.
        Taniwha 5y ago
        May also be an American thing (at least the whole spending a lot of time on analogies for SAT testing thing)
- aaronblohowiak 5y ago
  Fantastically written summary, thank you!!
- jl6 5y ago
  I didn’t quite get the climate science impact. Is the suggestion that these borgs currently are “digesting” methane, and therefore helping reduce the amount of methane released to the atmosphere? Is there a suggestion that we might augment them to “digest” CO2 too?
  - developer93 5y ago
    Methane is a more harmful greenhouse gas than CO2
- twic 5y ago
  Plasmids are an absolute doddle to work with. Borgs are huge, which makes them a nightmare to work with. I used to work with bacterial artificial chromosomes (BACs) that were ~100 kb in size, and those were already a pain. You have to be really delicate when preparing the DNA because it's so easy to shear. You can't separate it on a normal gel, you have to use PFGE. Borgs will be even worse. Borgs being bigger means you can fit more interesting stuff into them. But i don't know to what extent that is a constraint at the moment. 100 kb is already a lot of space for bacteria! Bacteria and eukaryotes are different enough that we won't find borgs themselves in eukaryotes, and if you put a borg into a eukaryote, it wouldn't replicate. However, they could be used as a vector for constructing human artificial chromosomes - you need something that replicates in working organism, like bacteria or yeast, so you can do the molecular biology, and you add the necessary human sequences to that: https://www.nature.com/articles/gt2009102 https://www.nature.com/articles/gt2009102 At the moment, the biggest vectors we have are yeast artificial chromosomes, which i think top out at ~1 Mb. But again, what are you going to do that needs that much space? A typical human gene is a few tens of kb; 40 kb is big (there are megabase freaks, but they are very rare). And that's for the gene, introns and all - often you can use a cDNA which is a fraction of the size.
- bigbillheck 5y ago
  > (Not really related, but many of our genes, and indeed one of our critical organelles, are also archea-derived, ie. the mitochondria.) Mitochondria are related to Rickettsia, which is a bacteria.
ImaCake 5y ago
I don't think it is as big a discovery as CRISPR. These are very cool, but in a basic science sort of way. The unknown proteins may be massively useful for methane processing, but no one knows that at this point. There are similar, although much smaller, genetic elements such as plasmids and BACs which could fill a similar role anyway. I don't see what could make this a really big deal outside microbiology yet. But maybe someone else will see what I am missing.

echelon 5y ago

They found a bacteria with extra-genomic material that isn't in the shape of a plasmid (circular DNA that is a feature of bacterial transfection and gene transfer). They believe it came from archean rather than bacterial sources. (Not really related, but many of our genes, and indeed one of our critical organelles, are also archea-derived, ie. the mitochondria.) The genomic payload is large and comes with replication machinery (it might be a useful tool!) Plasmids hold a much smaller payload than these units, and they're difficult to work with. Borgs are huge. If we can turn them into transfection toolkits, we can do larger scale genomic experiments much faster. That's extremely exciting. Much of biochemistry research and understanding is done in bacteria. They're extremely useful little computers. We just discovered an extremely useful way to hack them. In the wild, the gene payload codes for novel methane metabolic pathways. This also is of great interest. Not only for applicability to climate science, but also the natural ability to swap out or augment bacterial metabolism. Imagine all of the novel things you might swap in instead. Who knows. These might wind up in eukaryotic cells too!

deleted 5y ago
[deleted]
dnautics 5y ago
Noncircular extragenomic dna in bacteria isn't a new thing, for example, the marine algae cyanothece has linear DNA, and iirc it is important in regulating day/night cycles for nitrogen fixation (which is oxygen sensitive)
jkhdigital 5y ago
Wild stuff. Here's my current mental analogical model: bacterium : animal :: computer : botnet
- canadianfella 5y ago
  What do you mean?
  - echelon 5y ago
    You can often tell someone's age by whether or not they know analogies in this format. It used to be a staple of standardized testing on logical deduction. A : B :: C : D Is read as A is to B as C is to D. The reader is meant to understand the relationship between A and B and how it's similar to the relationship between C and D. An easy one might be, basketball : hoop :: hockey puck : net But they can get quite challenging. And with multiple choice answers present in standardized testing, you often have to understand the complex relationships between many abstract concepts, and evaluate that the abstractions are of a similar type or degree. They're actually kind of fun. Here's an example taken from [1] (the source also has excellent discussion as to why they were removed) : PALTRY : SIGNIFICANCE :: A. redundant : discussion B. austere : landscape C. opulent : wealth D. oblique : familiarity E. banal : originality Pick the correct answer A-E. [1] https://blog.prepscholar.com/sat-analogies-and-comparisons-why-removed-what-replaced-them https://blog.prepscholar.com/sat-analogies-and-comparisons-w...
    - drdeca 5y ago
      Is this an age thing? I’ve been surprised a number of times by people not being familiar with this format, but they were only a year or 2 younger than me. (I’m 25) It’s a nice format for thinking about things, so if people stopped learning it, that seems unfortunate to me.
      - Taniwha 5y ago
        May also be an American thing (at least the whole spending a lot of time on analogies for SAT testing thing)
aaronblohowiak 5y ago
Fantastically written summary, thank you!!
jl6 5y ago
I didn’t quite get the climate science impact. Is the suggestion that these borgs currently are “digesting” methane, and therefore helping reduce the amount of methane released to the atmosphere? Is there a suggestion that we might augment them to “digest” CO2 too?
- developer93 5y ago
  Methane is a more harmful greenhouse gas than CO2
twic 5y ago
Plasmids are an absolute doddle to work with. Borgs are huge, which makes them a nightmare to work with. I used to work with bacterial artificial chromosomes (BACs) that were ~100 kb in size, and those were already a pain. You have to be really delicate when preparing the DNA because it's so easy to shear. You can't separate it on a normal gel, you have to use PFGE. Borgs will be even worse. Borgs being bigger means you can fit more interesting stuff into them. But i don't know to what extent that is a constraint at the moment. 100 kb is already a lot of space for bacteria! Bacteria and eukaryotes are different enough that we won't find borgs themselves in eukaryotes, and if you put a borg into a eukaryote, it wouldn't replicate. However, they could be used as a vector for constructing human artificial chromosomes - you need something that replicates in working organism, like bacteria or yeast, so you can do the molecular biology, and you add the necessary human sequences to that: https://www.nature.com/articles/gt2009102 https://www.nature.com/articles/gt2009102 At the moment, the biggest vectors we have are yeast artificial chromosomes, which i think top out at ~1 Mb. But again, what are you going to do that needs that much space? A typical human gene is a few tens of kb; 40 kb is big (there are megabase freaks, but they are very rare). And that's for the gene, introns and all - often you can use a cDNA which is a fraction of the size.
bigbillheck 5y ago
> (Not really related, but many of our genes, and indeed one of our critical organelles, are also archea-derived, ie. the mitochondria.) Mitochondria are related to Rickettsia, which is a bacteria.

ImaCake 5y ago

I don't think it is as big a discovery as CRISPR. These are very cool, but in a basic science sort of way. The unknown proteins may be massively useful for methane processing, but no one knows that at this point. There are similar, although much smaller, genetic elements such as plasmids and BACs which could fill a similar role anyway. I don't see what could make this a really big deal outside microbiology yet. But maybe someone else will see what I am missing.