New Progress In The Quest To Control Cells, Wirelessly.

in #steemstem6 years ago

...Controlling Cells...Wirelessly?


Yes, you read that correctly. Scientists seek to be able to control specific cellular functions with out having to use machines and wires. It's an interesting concept that seems like science fiction. However the discovery of the protein EPG from the fish Kryptopterus bicirrhis puts humanity one step closer to making that dream a reality.

Kryptopterus bicirrhis: aka the glass catfish

Today we will discuss some research published in the journal Nature Scientific Reports titled "Wireless control of cellular function by activation of a novel protein responsive to electromagnetic fields." In this article the authors describe their work on the EPG protein, a protein which responds to electromagnetic fields.

It has long been known that Kryptopterus bicirrhis respond to magnetic fields, with research going back as far as the 1960's describing that this magnetic sensitivity is due to a specific organ, located under the fins of the fish. [2]. This organ has a variety of calcium channels, that become activated upon exposure to any magnetic field, which results in those cells having an increased influx of calcum. It is through this calcium influx that the fish to be able to detect the magnetic field.

EPG

Image Reproduced From [1] Figure 1A

In the article we discuss today, the authors were searching for the protein which results in the activation of the calcium ion channels, and respective influx of calcium. However, they first gave a very nice demonstration of the responsiveness of the Kryptopterus bicirrhisto a magnetic field. We see in the figure to the right in A the fish are swimming in all directions happily. In B the magnetic field is turned on (on the green plant side) and the fish all swim away from it and orient themselves in the same direction. Finally in C, the magnetic field is turned off and the fish resume swimming every which way. Cool right?

To identify the protein responsible for inducing this phenomenon the researchers turned to some molecular biology trickery and extracted the mRNA from the electro responsive organ (aka all the genes being expressed) they then classified all the genes based on sequences available in the GenBank database and removed non-relevant genes. Finally they took a smaller subset and measured current response by a technique called Two-electrode voltage clamp analysis.

From this they found a small peptide of 133 amino acids that was exceedingly responsive to the current. They named this protein electromagnetic perceptive gene or EPG. They performed a variety of bioinformatic characterization steps on this peptide, however did not do the most interesting experiment that I would have done. Utilized CRISPR to knock the gene out of Kryptopterus bicirrhis and see whether or not the fish lost its perception to magnetic fields. (ah well, I guess that's work for another group to do, or another publication.)

Next Steps

Following this, the authors expressed the EPG protein in human embryonic kidney (HEK293) cells:


Image reproduced from [1] Supplemental Figure 4

Here they were able to show that the EPG protein largely ends up in the membrane of the cells. The image above shows in green a stain for the protein cadherin (which is a membrane protein, that helps cells stick to one another), in blue is a DAPI stain (which stains the nucleus, as it binds to thymine bases in DNA), in red they show the fluorescently labeled EPG protein they expressed and finally they overlaid all three images together. We can see that in the EPG squares (the top is no expression of EPG and we see background fluorescence, and the bottom is when expression of the EPG is turned on) that when EPG expression is turned on, it accumulates in the same places as the cadherin, which is the cellular membrane.

The researchers then tested whether their fluorescent EPG could respond in the mammalian cells upon exposure to a magnetic field:


Image reproduced from [1] Figure 2 B and C

On the left we are looking at fluorescence prior to a magnetic field pulse, while on the right we see the fluorescence after a 10 second pulse. The darker red color is more fluorescence and as we see, fluorescence from the tagged EPG protein goes way up in the mammalian cell, after magnetic stimulation. The researchers also determined that this fluorescence coincided with a release of calcium ions from the cells (data not shown).

Can this protein be expressed in rat neurons?

It sure can, the researchers utilized lentivirus to deliver the fluorescently tagged gene to rat neurons (which we can see below on the left hand image with the green glowing neuron).


Image reproduced from [1] Figure 3 D, E and F

Researchers then asked whether or not the EPG protein caused a calcium response in the neurons upon exposure to a magnetic field. AKA did EPG make the neuron electromagnetic sensitive? This is what we are looking at above in the middle and right pannels. These pannels are looking at calcium concentrations through use of a calcium sensitive dye. The middle pannel is the calcium loaded neuron, and the right pannel is after 10 seconds of exposure to a magnetic field. We see that the fluorescence goes way up (it gets bright!) indicating that calcium is released from the neuron.

Yes! The expression of the protein in the neuron results in that neuron becoming sensitive to magnetic fields.

Can we make a mouse leg twitch...wirelessly?

Image reproduced from [1] Figure 4 C

If you have learned anything from the above sections, when I ask a question in the title the answer is (at least in this piece) yes. The researchers transfected the gene into motor neurons into the right primary motor cortex of the rats (aka it should control the left limb only). They then measured the electrical potentials of both the neurons going to the right and left limbs upon exposure to a magnetic field and viola, you get what we see to the left. The left limb had an electrical response, but the right did not.

The researchers were able to wirelessly, through an electromagnetic field, control the functioning of the neurons in a specific part of the rat.


Pretty wild research, if ya ask me!

Cited Sources

  1. https://www.nature.com/articles/s41598-018-27087-9
  2. https://www.nature.com/articles/199088a0

Cited Images

Image 1

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That is pretty epic research , science always amazes me . The fact that they are able to actually control over the neurons

Yeah it's really neat!

Great to see you posting regularly! I can't believe I missed your last few, but I haven't visited Steemit routinely these past few weeks.

Definitely a cool article. I agree that knocking out the gene in the Fish would have helped complete the story, but the fact that a mammalian muscle can be engineered to respond to magnets is amazingly cool.

but I haven't visited Steemit routinely these past few weeks.

Its hard to juggle all of life and being here too, I get it, trust me.

Hows Buffalo? Job is going well?

Yeah, certainly a weird protein function. I did not know that such a thing existed before reading the publication.

Buffalo is great. Its been a heck of a lot of work both managing the job and moving into/setting up a new house, but I'm almost at the point where the house is how I like it.

Job is picking up steam. I'm going through a bunch of small research projects at the moment which is good at establishing myself as someone who can accomplish tasks, but hard to really sink my teeth into something.

Coincidentally, I'm also writing an article about something magnet related so keep an eye out for that.

Glad things are coming together for you man! It takes time to get a new situation to where you'd like it.

Well I hope you will make at least one ICP reference in that magnet post. Fuckin magnets, how do they work?

Oh I have a feeling ICP will make an appearance :)

Very interesting research, I read something similar these days, about devices implanted in the body that could be controlled at a distance despite the fact that the devices did not have any batteries, such a good research.

Those devices sound interesting as well.

Great job translating the original articles into a cool Steemit post!

My goal is to expose more people to primary research data. :)

Its hard to read the actual papers for people though. So I simplify that a bit.

I agree. I had some original research that was lost and/or deleted but never published because it was an internal project commissioned by the NPS. Using Steemit I was able to resurrect the data from old backups and make it available to my colleagues and those who might need the data in the future. For most Steemit posts, I agree we have the obligation to present science to those who might not otherwise see it, and to present it in a way that will arouse interest in the subject material as well as the platform.

All scientists have that obligation. What good is what we do if people can't learn something from it? Well... Other then the life saving aspect of course.

In Fig 1A (B) the fish acts as a magnetic domain when an external field is applied. This progress is nature meeting physics, an exciting frontier in the field of science.

right hand rule anyone?

This is a Totally Awesome development... Thinking of the benefits to individuals who have been paralyzed from the neck downwards may be by a severed spinal cord.
The potential goes on and on.

Yeah, lots can come out of this work, however there are a lot of very basic things to still understand.

Guess that's why they tested it in such a wide range of animal cells, I've never seen the phrase "1:50 costume made rabbit anti EPG antibody" before lol.

Oh, just a special antibody, not a furry suit!

Yes! I get the idea now. Thanks

calcium response in the neurons upon exposure to a magnetic field

So simple and so elegant... And a little bit frightening...

As all good science is

Hello @justtryme90

Certainly and interesting and exciting research. Very detailed enough for even a doubting Thomas to believe. I wonder how this would be replicated in humans. Perhaps the specific gene will be isolated and inserted into a specific part of human body for the purpose of wireless control of the part of body involved, or...? (what's the possibility, can you help me out; want to understand the concept?).

Regards.

@eurogee of @euronation and @steemstem communities

I don't know what the possibility will be from this particular protein. Obviously one can use it to control the firing of calcium ion channels by inducing a magnetic field. So like they tested here, you can use it to induce nerve firing. What could one do with that? :)

Do with nerve firing...? Well, I seem to be loss here. But let me make a guys🤔

Can't fathom anything sir.

What about helping people with nerves that don't fire properly?

You are right! I read this in @zests comment and I immediately agreed with him. Yes you re right. Thanks✌️

Of course. Thanks for reading :)

I was aware of optogenics, but not this. I'm already dreaming up ideas for how to use it, if it can be expressed in prokaryotes.

Glad to see you mentioned GenBank too, this is a good example of how having a publicly available database of previous research, in a machine readable format, can help with unraveling current mysteries (or, as you put it more succinctly, 'trickery').

if it can be expressed in prokaryotes

Its a membrane protein, so it would likely not be as useful in prokaryotic organisms.

A little embarrassed to not have considered that. Then again, it's just an opportunity to isolate the active site in a non-membrane bound portion or play around with embedding in in planctomycetes (ha, right).

Indeed, there is the potential for domain fusions with other proteins of interest, but considering the structure of this one, I don't know if that's possible. Only more research will let us know.

Ok, this has to be the most interesting article I have read in the last few days, setting you as a real example here.
I am a huge fan of IoT and I thought of many implementations but this is something I missed before.
Amazing ideas come to me with this and the future. Could we call T-cells on command or block some receptors, copying or simulating the CCR5 mutation to prevent HIV from getting a hold of any cell?
The options.... !

Glad you enjoyed it, there are some fascinating protein functions out there. Who knows what we will find out next and what applications may come forth.

Good questions, I don't have an answer for them.

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