Protein that chikungunya virus uses to get into cells is identified

If we can block this interaction, we'd block virus infections.

Read the whole story

 

[ylk1]

Nice!

 

[Tmptfate]

But will it block the Proto-molecule? These are the important questions!

In all seriousness though, that sounds promising. Pairing it with additional methods could make big changes in how we fight viruses.

 

[alastairmayer]

So what (other) purpose does Mxra8 serve in cells? Is blocking it going to cause other problems?

 

[jamesonista]

CRISPR-Cas9 DNA editing system to delete more than twenty-thousand mouse genes

Quite the brute force method for DNA. Glad to hear it was successful.

 

[samanime]

Is this a common technique nowadays?

It sounds like a great idea to use as a starting point for researching just about any type of infection.

As a software developer, it aounds like unit testing to me, which has greatly improved that industry now that it's commonplace.

 

[Kilroy420]

So what (other) purpose does Mxra8 serve in cells? Is blocking it going to cause other problems?

This is why they have to run trials in labs against various mammals to determine efficacy and whether there are any detrimental side-effects.

 

[rochefort]

So what (other) purpose does Mxra8 serve in cells? Is blocking it going to cause other problems?

It's unlikely that a protein that humans have four copies of doesn't have a function that's important in at least some circumstances.

In this case, it might be important for forming or sustaining the blood-brain barrier:
https://www.omim.org/entry/617293.

 

[rochefort]

Is this a common technique nowadays?

It sounds like a great idea to use as a starting point for researching just about any type of infection.

As a software developer, it aounds like unit testing to me, which has greatly improved that industry now that it's commonplace.

This kind of technique has been used in easily engineered organisms, like E. coli and yeast, for a long time. CRISPR-Cas9 is making it more accessible for complex organisms.

 

[rochefort]

CRISPR-Cas9 DNA editing system to delete more than twenty-thousand mouse genes

Quite the brute force method for DNA. Glad to hear it was successful.

If they used a binary search to isolate the gene, they may have needed to inspect just 15 petri dishes to narrow their search form 20,000 to 1 gene.

I'm not sure I completely understand what you mean by a binary search, but if you mean something like a git-bisection (which I only somewhat understand), I think the requirement that the cells be alive isn't compatible with that strategy.

Now, if you already have, say, some mouse cells that you know are immune to the virus and others that are susceptible, then there are lots of ways of identifying the gene in question. That's what a lot of genetics had traditionally been about.

 

[FireAndTheVoid]

CRISPR-Cas9 DNA editing system to delete more than twenty-thousand mouse genes

Quite the brute force method for DNA. Glad to hear it was successful.

If they used a binary search to isolate the gene, they may have needed to inspect just 15 petri dishes to narrow their search form 20,000 to 1 gene.

Binary searches require that the data set has already been sorted. That is certainly not the case with genes.

 

[Ashakar]

CRISPR-Cas9 DNA editing system to delete more than twenty-thousand mouse genes

Quite the brute force method for DNA. Glad to hear it was successful.

If they used a binary search to isolate the gene, they may have needed to inspect just 15 petri dishes to narrow their search form 20,000 to 1 gene.

you can't use a binary search for what they were trying to do. You need a numerically sorted data set and after each search you need to be able to tell if what your looking for is greater or less than your initial search target.

 

[RickyP784]

Researchers used the CRISPR-Cas9 DNA editing system to delete more than twenty-thousand mouse genes—a different one in each cell in a dish.

That's a lot of petri dishes for a brute force solution, wow. Props for dedication and organizational skills keeping all that shit straight.

(ninja'd by jamesonista)

 

[Tofystedeth]

CRISPR-Cas9 DNA editing system to delete more than twenty-thousand mouse genes

Quite the brute force method for DNA. Glad to hear it was successful.

If they used a binary search to isolate the gene, they may have needed to inspect just 15 petri dishes to narrow their search form 20,000 to 1 gene.

you can't use a binary search for what they were trying to do. You need a numerically sorted data set and after each search you need to be able to tell if what your looking for is greater or less than your initial search target.

Everyone knows biologists use bubble sort.

 

[NinjaNerd56]

Paging Captain Trips....

...Captain Trips, please pick up the black Apocalypse phone.

/rs

 

[JamesKPolkEsq]

Therapy is a monoclonal antibody - a transient therapy to a specific viral infection.

It's not a permanent blockade, since the half-life of a therapeutic antibody is relatively short.

It would be a great antiviral for some infections, but not a silver bullet against viruses by any means.

 

[Hyoubu]

So this would a potentially new target within a known target category for anti-virals, specifically the adsorption stage of a virus' life cycle. Another type of drug that targets at this stage is drugs that target CD4, a transmembrane protein which is present on the surface of our T-cells. These drugs aren't on the market yet. This sites mentions a drug that would be potentially used: https://www.id-hub.com/2017/09/21/new-d ... 4-t-cells/

Overall, this is interesting, but I don't doubt it will be a long time until we see this on the market. The other thing is that this part of a virus isn't often targeted and so could be coupled with other anti-virals for more effective overall treatment prognosis. This is because you can target two different stages simultaneously for increased effectiveness (there is a word for the approach but I can't remember).

 

[FireAndTheVoid]

CRISPR-Cas9 DNA editing system to delete more than twenty-thousand mouse genes

Quite the brute force method for DNA. Glad to hear it was successful.

If they used a binary search to isolate the gene, they may have needed to inspect just 15 petri dishes to narrow their search form 20,000 to 1 gene.

you can't use a binary search for what they were trying to do. You need a numerically sorted data set and after each search you need to be able to tell if what your looking for is greater or less than your initial search target.

Everyone knows biologists use bubble sort.

I prefer the Quantum Bogo Sort.

http://wiki.c2.com/?QuantumBogoSort

 

[Fatesrider]

So what (other) purpose does Mxra8 serve in cells? Is blocking it going to cause other problems?

Ah, but you see, we don't need to block it in people.

We really only need to add it to mosquitoes.

If the virus attacks the vehicle by which it's transmitted, then the whole cycle will be disrupted. It might not STOP all incidents of the transmission, but it would be a whole lot easier to do than vaccinate the globe.

Of course, testing that theory out would have to be done, but I'd look at altering the mechanism that spreads it first before thinking about screwing around with the genomes of, well, every other animal on earth (or so it seems). Kill the mosquito faster and fewer people/animals/etc. will become infected. If the mosquito develops an immunity to the virus, then we can see how that might be added to people/animals (as opposed to taking away things from the human/animal genome).

Just a thought there...

 

[alastairmayer]

CRISPR-Cas9 DNA editing system to delete more than twenty-thousand mouse genes

Quite the brute force method for DNA. Glad to hear it was successful.

If they used a binary search to isolate the gene, they may have needed to inspect just 15 petri dishes to narrow their search form 20,000 to 1 gene.

Binary searches require that the data set has already been sorted. That is certainly not the case with genes.

No they don't. You're thinking of the special case of an ordered list.

OP is thinking of something like the old puzzle: given 16 identical-looking coins where one is fake (different weight) and a balance scale, what's the minimum number of weighings to find the bogus coin?

You don't need them sorted, and it is a binary search.

The problem, though, as rochefort suggests, is trying something like that might kill the mouse cells due to deleting too many genes.

 

[The DCG]

Edit: never mind, I misread the post I was replying to. Mea culpa.

 

[Plorkie]

CRISPR-Cas9 DNA editing system to delete more than twenty-thousand mouse genes

Quite the brute force method for DNA. Glad to hear it was successful.

If they used a binary search to isolate the gene, they may have needed to inspect just 15 petri dishes to narrow their search form 20,000 to 1 gene.

you can't use a binary search for what they were trying to do. You need a numerically sorted data set and after each search you need to be able to tell if what your looking for is greater or less than your initial search target.

If this were a simple thing, you could delete 1/10 of the genes in each dish and then focus only on the ones that showed improvements, but... This process sounds fiendishly complicated and if you eliminate that many genes at once, it's hard to tell if there wasn't some other kind of complex interaction.
If only genetic code were as easy as computer code.

 

[theotherjim]

So what (other) purpose does Mxra8 serve in cells? Is blocking it going to cause other problems?

It's unlikely that a protein that humans have four copies of doesn't have a function that's important in at least some circumstances.

In this case, it might be important for forming or sustaining the blood-brain barrier:
https://www.omim.org/entry/617293.

Found same in a quick search. Screwing with the blood-brain barrier is not a small thing. Even transiently. On the other hand, this might be a cancer-like case where e.g. an added risk of fatal brain infections (to say nothing of hitherto unseen drug-drug interactions) is a tolerable risk compared to the certainty of the alternative.

Could not quickly find any info on whether anybody has done a mxra8 -/- deletion mutant in mice, and whether and/or at what stage it's lethal.

Interesting, but a helluva long way away from a treatment. But maybe a signpost.

 

[tomca13]

I find it amazingly cool and simultaneously slightly sad that we are still at the stage of figuring out how viruses infect cells.

 

[alastairmayer]

CRISPR-Cas9 DNA editing system to delete more than twenty-thousand mouse genes

Quite the brute force method for DNA. Glad to hear it was successful.

If they used a binary search to isolate the gene, they may have needed to inspect just 15 petri dishes to narrow their search form 20,000 to 1 gene.

you can't use a binary search for what they were trying to do. You need a numerically sorted data set and after each search you need to be able to tell if what your looking for is greater or less than your initial search target.

No you don't. See above. Get your mind out of the computer data structure and into the real world.

All you need is a "does this set contain a sample that meets the criterion I'm looking for?" function.

In the puzzle example, you compare the total weight of a subset against another subset. In the specific case, it's "which cells succumb to the virus, those without genes A, B, C, and D, or those without genes W, X, Y and Z?" Subdivide and repeat. At each step you eliminate half the genes.

 

[FireAndTheVoid]

CRISPR-Cas9 DNA editing system to delete more than twenty-thousand mouse genes

Quite the brute force method for DNA. Glad to hear it was successful.

If they used a binary search to isolate the gene, they may have needed to inspect just 15 petri dishes to narrow their search form 20,000 to 1 gene.

Binary searches require that the data set has already been sorted. That is certainly not the case with genes.

No they don't. You're thinking of the special case of an ordered list.

OP is thinking of something like the old puzzle: given 16 identical-looking coins where one is fake (different weight) and a balance scale, what's the minimum number of weighings to find the bogus coin?

You don't need them sorted, and it is a binary search.

The problem, though, as rochefort suggests, is trying something like that might kill the mouse cells due to deleting too many genes.

It sounds like you are suggesting deleting more than one gene at a time. Genes interact with one another (see https://en.wikipedia.org/wiki/Epistasis) and deleting certain combinations of genes doesn't necessarily indicate the effect of deleting an individual gene. So, no, I still don't think a binary search is relevant in this context.

 

[breakaway01]

Researchers used the CRISPR-Cas9 DNA editing system to delete more than twenty-thousand mouse genes—a different one in each cell in a dish.

That's a lot of petri dishes for a brute force solution, wow. Props for dedication and organizational skills keeping all that shit straight.

Actually the strength of this type of screen is that it is a "pooled" screen. You don't have to separate all of the genes from one another. All of the cells are mixed together so that you can run a screen like this on a small number of dishes. You just target the cells so that on average, each modified cell has been knocked out at a single gene. Then you challenge with virus and sort out the cells that aren't infected. These uninfected cells are likely to have been knocked out at genes essential for viral infection, which you can then identify by sequencing.

 

[Jackattak]

Forgive my ignorance, but are viruses not alive themselves, thus just as prone to evolution as all life? Would they not eventually develop a new pathway?

 

[not trending]

I'd wager that if we blocked one access way, over time the virus would make another adhesion molecule do its bidding.

Them there viruses ain't no fools.

 

[kkeane]

CRISPR-Cas9 DNA editing system to delete more than twenty-thousand mouse genes

Quite the brute force method for DNA. Glad to hear it was successful.

If they used a binary search to isolate the gene, they may have needed to inspect just 15 petri dishes to narrow their search form 20,000 to 1 gene.

I don't think they used binary, or any, search at all. The way I understand it, they simply mix all the various cells together in a single brew, add the virus, and then (somehow, though something like magic) filter out those which got infected. Then you figure out which genes were knocked out in the "survivors".

 

[kkeane]

Forgive my ignorance, but are viruses not alive themselves, thus just as prone to evolution as all life? Would they not eventually develop a new pathway?

That depends. Sometimes, viruses (and bacteria) develop new pathways; that's how drug resistance evolves.

But sometimes that doesn't happen. It all depends on if there is an alternate pathway available, and how few or many modifications the virus needs.

Kind of how (some) humans have evolved lactose tolerance, but no mammal has evolved resistance to, say, drowning - even dolphins or whales can drown eventually.

 

[peragrin]

Forgive my ignorance, but are viruses not alive themselves, thus just as prone to evolution as all life? Would they not eventually develop a new pathway?

a virus can't mutate a new pathway into your body. what it can do is mutate to use another pathway. but that isn't as efficient or maybe as useful.

a variation of this technique is being used to potentially block the common cold. every single version of the hundreds of variations.

 

[Veritas super omens]

Forgive my ignorance, but are viruses not alive themselves, thus just as prone to evolution as all life? Would they not eventually develop a new pathway?

Virus do evolve but their "alive" status is an open question. Depends on your definition of life. They require the cell machinery of their host in order to replicate. They might develop a new pathway, but this is just the very first steps in finding a treatment or prevention. If you can prevent them from entering a cell, that WILL end their ability to evolve along that pathway, as they MUST have the cellular machinery in order to replicate. No entrance into cell yields no replication, so no evolution.

 

[odikweos]

So what (other) purpose does Mxra8 serve in cells? Is blocking it going to cause other problems?

Ah, but you see, we don't need to block it in people.

We really only need to add it to mosquitoes.

If the virus attacks the vehicle by which it's transmitted, then the whole cycle will be disrupted. It might not STOP all incidents of the transmission, but it would be a whole lot easier to do than vaccinate the globe.

Of course, testing that theory out would have to be done, but I'd look at altering the mechanism that spreads it first before thinking about screwing around with the genomes of, well, every other animal on earth (or so it seems). Kill the mosquito faster and fewer people/animals/etc. will become infected. If the mosquito develops an immunity to the virus, then we can see how that might be added to people/animals (as opposed to taking away things from the human/animal genome).

Just a thought there...

It would be so much simpler to turn all this effort to finding a solid way to kill all the mosquito (and tick!) species that plague us.

 

[Nowicki]

So what (other) purpose does Mxra8 serve in cells? Is blocking it going to cause other problems?

Ah, but you see, we don't need to block it in people.

We really only need to add it to mosquitoes.

If the virus attacks the vehicle by which it's transmitted, then the whole cycle will be disrupted. It might not STOP all incidents of the transmission, but it would be a whole lot easier to do than vaccinate the globe.

Of course, testing that theory out would have to be done, but I'd look at altering the mechanism that spreads it first before thinking about screwing around with the genomes of, well, every other animal on earth (or so it seems). Kill the mosquito faster and fewer people/animals/etc. will become infected. If the mosquito develops an immunity to the virus, then we can see how that might be added to people/animals (as opposed to taking away things from the human/animal genome).

Just a thought there...

It would be so much simpler to turn all this effort to finding a solid way to kill all the mosquito (and tick!) species that plague us.

But if you leave current species of mosquitos who dont pose a threat, they can pick up the same genes and or other diseases can adapt to infect other species of mosquitos.

The alternative of killing all the bugs isnt viable either. Our best hope is to find the key genes/proteins that keep it *the disease* ticking, or allow it to infect, and address those directly.

 

[nartreb]

Forgive my ignorance, but are viruses not alive themselves, thus just as prone to evolution as all life? Would they not eventually develop a new pathway?

Natural selection does not dictate that an organism will adapt to a new challenge. Natural selection means only that one of two things will happen:
a) Rare organisms that can overcome the challenge will increase as a proportion of the population
[usually at some cost to overall fitness (otherwise these variants wouldn't be rare), thus usually resulting in at least a temporary decline in total population numbers],

or


b) resistant individuals are non-existent or too rare to sustain a viable population , and so the whole population goes extinct.

Jeff Goldblum notwithstanding, life doesn't always find a way. At least, a particular species often doesn't. In the grand scheme of millions of species and billions of years, though, it's a pretty good rule of thumb.

In this particular case it's very hard to make any predictions. There are lots of ways of becoming resistant to a treatment targeted at this adhesion molecule: use a different adhesion molecule, produce an enzyme that destroys the treatment drug, ... I wouldn't place any bets yet.

 

[Oak]

So what (other) purpose does Mxra8 serve in cells? Is blocking it going to cause other problems?

It's unlikely that a protein that humans have four copies of doesn't have a function that's important in at least some circumstances.

In this case, it might be important for forming or sustaining the blood-brain barrier:
https://www.omim.org/entry/617293.

Huh... the NIH requested the OMIM project diversify it's revenue stream? Or is that just a way of saying "The NIH is no longer granting us sufficient funds"?

 

[whobeme]

CRISPR-Cas9 DNA editing system to delete more than twenty-thousand mouse genes

Quite the brute force method for DNA. Glad to hear it was successful.

If they used a binary search to isolate the gene, they may have needed to inspect just 15 petri dishes to narrow their search form 20,000 to 1 gene.

you can't use a binary search for what they were trying to do. You need a numerically sorted data set and after each search you need to be able to tell if what your looking for is greater or less than your initial search target.

Not true, at least not generally true. Let's assume that there is a single target gene which rescues, and let's arbitrarily let it be the first cell line. Number the cell lines 1 to 20000. Put 1 to 10000 into one plate, the rest into another. Test. The first plate has live cells. Put 1 to 5000 into one plate, 5001 to 1000 into the next, and so forth. Voila, binary search. The cell lines don't really need to be numbered of course, they just need unique names that can be sorted into some order.

In reality a few cells are likely to survive from various cell lines due to chance or random spontaneous mutations of the resistance gene, so that simple method won't work.

What they most likely did was to plate the cell lines one to a well in multiwell dishes, hopefully using a robot of some sort to do all the pipette work. There are lots of sizes available, here is the first picture I found showing some together:

https://spllabware.en.ec21.com/SPL_Cell ... 19961.html

 

[Ralf The Dog]

So what (other) purpose does Mxra8 serve in cells? Is blocking it going to cause other problems?

Other people have answered this. Let me do so from a different perspective. Not having Mxra8 would provide a great advantage in that not having it would provide resistance to viral infection. If many species have it or something like it, Mxra8 must provide some great advantage. Great enough that individuals that don't have it do not survive to breed.