On Microbiology


#1

Continuing the discussion from Dildo throwing rebels hold Paiute artifacts hostage, refer to native peoples as "savages":

Yeah, man, i totally agree! Microbiology is an endlessly entertaining and fascinating subject.


#2

I like stromatolites!


#3

Definitely. As close to the molecules as you can get without the higher levels getting in the way.

For some weird reason, arses in videogames get much more attention than they’d deserve, and same goes for a bunch of yahoos in the middle of nowhere.

What about said bacteriophages? What about e.g. phage therapy, it may be useful now when even the last-resort antibiotics tend to not work?

Or use of silver nanoparticles either standalone or in conjunction with conventional antibiotics?

Or even “DNA printers” for quick on-demand preparation of gene-modded microorganisms to produce substances? Or use of the Lactobacillus instead of E.coli in such applications as then all you’d need to make what you need is a yoghurt-making machine and a rig for extraction/purification?


#4

Phage therapy is one of the most frusterating technologies that’s never taken off.

When it works, it works beautifully, but there’s a lot of technical reasons why it’s not in widespread use:

  • Each phage only infects one or a very few strains of just one species of bacteria. They are extremely specialized, so in any general use, you’d need either a product with a ton of different kinds of phage, or to know the exact strain of bacteria the patient is infected with and have the counter-phage on hand.
  • Culturing viruses is very difficult. Storing them may be even more difficult. The therapy is incredibly expensive and requires meticulous monitoring. Antibiotics are easier, usually it’s just splice a gene for making that antibiotic into a yeast, and sit back while you count your money.

#5

I know absolutely nothing about storing viruses. Other than storing them up my nose and down my pants, of course. What makes phages and viruses difficult to store? Do they break down quickly if not in a medium they can infect?


#6

Well… Actually bacteriophages are evolved to hang out in the same environment as the cells they infect. And with phages, I wouldn’t expect them to be that hard to store. Those are tough little things. But Eukaryote-infecting viruses tend to be harder to store.

The big problem though is that all viruses are difficult to culture, purify and process. Phages are just really fucking tiny, and very picky about what they infect.


#7

So, they are jerks.

(I’d love to hear more from all y’all, I am fundamentally a nerd :D)


#8

I have very low comprehension of Microbiology so be nice to me, but this seems relevant… and cool. Sounds like some smooth peeps have been trying to get super positioning to work on micro organisms.

This article summarizes it quite well:


But the Guardian goes into more detail:
http://www.theguardian.com/science/2015/sep/16/experiment-to-put-microbe-in-two-places-at-once-quantum-physics-schrodinger


#9

So now each package of chorizo or smoky maple links that rolls down the smokehouse’s spotless conveyor belt gets a squirt of a bacteriophage product called Listex before being sealed.

also a great primer on phages


#10

My dad has a PhD in Microbiology - apparently his thesis was on nutritional and enzymic studies with methanol-utilizing bacteria.


#11

Generate the required DNA fragment to match the given germ cell, preferably in situ with said “DNA printer”, insert it to a “blank” phage (something that can grow on E.coli or a Lactobacillus or whatever is easy) via CRISPR, deploy the same day?

Bacteriophages are easier than most other viruses. No need for chicken embryos nor other crap.

…could tissue cultures be used for growing viruses? Something similar to the plaque titration?

How much of the annoyances and costs can be scaled and automated away?


#12

No idea.[quote=“shaddack, post:11, topic:72604”]
How much of the annoyances and costs can be scaled and automated away?
[/quote]
probably all of it, since that’s what pharmacology companies like Pfizer and GSK do.


#13

With enough of computing power, and good enough lab-on-a-chip systems, cures could be finely tailored for the patient - something that could kill somebody else could be beneficial for the given person. I suspect many of the spectacular drug failures due to side effects were due to the side effects being specific to some genetic variant of a given recipient, which could be addressed by this approach.

Take the genetic makeup of a given person, model the shape of all the cell receptors encoded there, model the strength of the interactions of the active principle and its metabolites, decide if it is a good fit or not.

If advanced enough, the approach could be used for designing drugs “on the fly”.

Thought… could some gene therapy vector be used for in vivo drug manufacturing? “Infect” cells with a mRNA encoding the protein we want, possibly use a vector specific only for certain kind of cells, and let it be translated into proteins we want? Kind of like how viruses work, but without complete hijacking of the cell and without transcription into its DNA? Then we could just make a given nucleic acid sequence and inject it where we want it, and let the already existing machinery make what we need without having to have the added in vitro expenses.

With the concept of DNA printers, we could try to move as much of the effort to using straight nucleic acids, perhaps with suitable vectors (could the vectors be self-generated the same way, too, using the in vivo resources for controlled multiplication?), without overly complex techology around and with just a few mass-produced feedstocks.


#14

Just read up on CRISPR. It has potential to do all of that stuff. It looks to me like a basic search and replace tool for genes, where previous gene therapies typically were akin to creating a whole extra chromosome in the mature cell containing the desired gene for a given therapy. Very messy, very difficult to figure out how it fits into gene networks and how promoters and inhibitors and methylation fits in.

With CRISPR you can search for an arbitrary sequence, snip it out in-situ, and then replace that sequence with any other sequence. Promoters, methylation, inhibition, histone wrapping can all be preserved. It’s a very good tool already, but it’s brand new and getting better. Pretty soon we’ll be able to write compile and execute genetic code as easily as we can computer code.


#15

I am toying with an idea of a DNA printer. An assembly of four subunits, each handling a string of polynucleotide as a feed. Each unit having two chromophores attached, one common for all four, one specific for the unit. The common one resets the subunit conformation, the specific one forces the subunit to attach one nucleotide to the output chain and cleave it off the feed string. Kind of like a light-controlled enzyme. Attach these units to a membrane with pores (self-assembly to the rescue!) or let them float on some other carrier to allow washing them with the polynucleotide solutions to load the assemblers and then to wash away the product.

Illuminate with sequence of color laser flashes. Get a DNA sequence, one molecule from each assembler, PCR-amplify if you need more, deploy as-is or splice it with CRISPR into a suitable carrier.

Couple with a “DNA microscope”, e.g. a membrane with a pore with couple carbon nanotubes around to serve as scanning tunnelling microscope probes. Isolate a molecule we want to test, pull it through the pore by e.g. concentration gradient or solvation, analyze the signals from the probes, reconstruct the molecule shape and therefore the order of bases and even methylations and other modifications (there’s a plethora of them, as the evolution cobbled together the first hack that was on hand every time something was needed, so the result is more complex than a cash-strapped process plant after couple decades).

Voila, an analysis-synthesis rig that could be in every small doctor office.

Add the in vivo synthesis tricks, and we’re off for interesting times. :smiley:


#16

Sounds to me like you want to reinvent the ribosome.


#17

Ribosome translates mRNA to proteins. The in vivo trick is feeding the cell with mRNA from the outside and letting the ribosomes present to do the job of an expensive protein-preparation rig.


#18

two highly relevant concepts from medicine/toxicology

(Effective Dose) ED50 - the dose that treats 50% of the study population.
(Lethal Dose) LD50 - the dose that kills 50% of the study population

It is ALL variation.

I think phages offer better solutions, but antibiotics are less work (more profitable)


#19

it is more than a two dimensional (AGTCTCTCGG) problem. There is also folding, and then select methyation, and some other things. But sure, yeah, someday


#20

There’s also the issue of therapeutic index. That is the ratio between a therapeutic dose and a lethal dose. Which is basically just the ED50:LD50 ratio.

The bigger the therapeutic index, the more useful the drug, since you can start out small and if that doesn’t work, go big.