• edited May 2012
    Yeah, I'm thinking an AAV in powder form. Then I'd snort the shit like cocaine everyday for a few weeks until it hits my retina.
  • Is there a way we can target genes to only activate in the retina? Although... what I know about targeted gene expression still requires you to put promoter genes in manually, and that puts us back to square one.

    Could we make our mod activate only where it finds retina-specific genes? Or, if we can't, is it possible to inject the mod into a blood vessel leading directly to the retina?
  • I hope that you'll forgive me this episode of thread necromancy, but I found several interesting scientific articles relative to gene-based retinal modifications.
  • i found a source to buy cryptochromes if you guys have some cash and are feeling adventurous!
  • slightly related, there are some people who can see in ultraviolet if the have a lens implant after getting a cataract (I think if the implant is slightly faulty is missing the UV coating), so could it be possible to have some way to reduce the anti-uv coating? Removing it completely would be very bad for your eyes, but removing a small amount so you can still detect it without it being too dangerous would be helluva cool 
  • I wrote up a little blog a while back about a different means of doing
    this. I'm not sure if its all that appropriate for my first post here to be a link, but it does eliminate much of the problems with trying to get your cells to express some novel gene:  

    3-dehydro retinol

  • Hey guys I've found a sea slug that manages to use chlorophyll as a symbiotic relationship with plants and here's the link.
  • i was always sad that this thread didn't progress further. Genetics is my focus so I think it's time I give this thread a good push while it's on the main page. so insert bump here I guess.

    As to useful information, I feel the aav vector is the best shot but what would be better is a temporary mod. Maybe a bit of mRNA to produce the proteins we want and use the aav to deliver it to where we want it. After enough exposure we measure the response to whatever wavelength we designed the thing to be responsive to.
  • peeks in thread and whispers: crispr...
  • i thought of that, obviously. but it'd be better to start with a temporary test than a perm mod
  • fair enough. better beta that ish...

  • I also have an idea that might turn out to be a problem.

    So I was reading my Biological Psychology book and in it it showed how when a person ost a finger the sensation ability of the near by fingers was greatly increased. So in turn what i earned from that was that is you might let say want to add another finger you would decrease sensitivity of nearby limbs unless you were able to make more space in the brain, or increase the power of the brain.image
  • Are you trying to say that increased activity in the eye might cause issues until the brains plasticity kicks in?

    If so, we've touched on this a few times, most recently with the NIR project. Added stimulus is folded into the brain and it adjusts fairly quickly.
  • Hey Glims 
    My point was rather that the increased stimulus from the eye may (Not 100% sure) over lap on to another sensory system, or it may decrease sensation of other systems nearby. 

  • We haven't seen any evidence of that, but i'm not discounting it. I would say that a little bit of increase in one area of the sensorium is not the same as adding an extra eye or finger or whatnot. Tetrachromacy is a thing, The brain can handle it.
  • ^seconded. there are now multiple account of tetra chromes and they see fine, and as expected, even better due to the extra colors and what not. the brain can take a fair bit, i feel it'd be fine. that said, only one way to find out. any takers? XD as to how to do this, could we first try synthesising some mRNA and dropping it into a cell line, see if the correct enzymes/pigments form? this is way over simplified i know but the point is there. once we do that we can go from there

  • make the plasmid, smack it into a bacteria, check for enzyme.

    quick question, how big is the photopigmentation sequence? DO we know what sequence we need?
    I'm pretty sure tetrachromacy comes from additional cone cells. Unless i'm mistaken, altering the photopigmentation is not the same thing, but it would be a good poc.

  • well it's additional cone cells sure, but they have to be sensitive to a different wavelength. and that is due to some form of pigmentation. Unless it's due to a structural difference but im doubtful of that if it could be induced in fish

  • Yes. Ok, so pigmentation mod.
  • now we just need to decide which pigment. Strictly speaking we can probably pick ones that aren't normal, as in we decide which wavelengths it's sensitive too. So do we want uv, IR, NIR, orange? once we know we can go form there
  • UV is structural, nir is getting played to death. What do you think will work?

  • I figured uv might be odd. Honestly i'm not sure. Current tetrachroms see extra shades of red. i'd have to see what pigment is responsible for it. If my suspisions are correct then it'll be a similar pigment to the normal red but the structure will be slightly different. that said, i feel blues could be the most interesting. So my bid is we try a blue and a red and see which works best. or at least research both and decide which is easiest to produce
  • so the question is more, has this thing been isolated before or are we doing an exploratory project here?
  • Of that I'm not sure. Since there aren't many tetrachromes i doubt they've done any sort of exploration into how it functions. that said, we could use tetrachromatic animals as a base as there are several. use one of their pigments. at least one of them should be well documenter
  • I don't know if this will be useful but this talks about sensitivity to near IR:

    I was looking for information on tetrachromatic and pentachromatic animals and I've only found birds (such as pigeons) and fish, and that's likely mostly structural and in the UV (Which would be great but humans have yellow lenses that naturally filter UV out).  In case some use could come of them I'll leave the links here:

    The link below should give a mathematical approximation for potential options.  If not the UV or NIR range for a new cone then maybe the space between where our blue and green cones are rather than a cone with a peak of 700-720nm?  A cone that peaks 497nm wouldn't be too shabby and I wouldn't doubt if there's an animal with such a cone.

  • i'm reading through a few papers based on your suggestion. i see no reason why birds should be excluded as candiadates as many ought to have been sequenced which makes them ripe for the picking as it were. im currently reading through a paper on ducks to see if it leads anywhere useful as to what the pigment is.
  • so as of yet i've found nothing since it seems no one has taken the time to identify the pigment itself, but i've learned a few things. so the pigments reside mainly in a tiny oil droplet at the tip of the cone. so whatever the pigment is, there will be some sequence in it's dna that'll export the pigment to that location. furthermore the pigments are similar in most birds so whichever has been sequenced is good enough. that said the export and synthesis genes could be very far ya if you had a genetics lab and were willing to put in the work you could extract hundreds of eyes from various mutants of a tetrachromatic species, identify which were lacking the pigment and then find which gene is missing. that sounds like a pain in the ass to me. so here's what i propose. we need to break this into a few sections. 

    part a: research

    part 1: determine what exports pigment into those oil drops. is it some sort of transporter? or does it get jammed in a vesicle and moved? also how does it know which cones to produce the pigment in?

    part 2: pick a pigment with a known synthetic pathway, even if it isn't normally an ocular pigment. all we need is one that we know can harvest light. plants may be useful for this.

    part 3: pigment biosynthesis. what's the pathway? what is the sequence of proteins needed to make it? what's the dna sequence?

    part b: off our asses, time to work

    put everything together and begin work on getting the synthesis part functioning in a bacteria. when we know it work we use a model organism to see if we can get it produced in a host animal, not necessarily the eye, just produced (we may end up with some blue rats lol). finally redirect it to only produce i the correct area. once that's all done we modify the delivery so that it can be delivered to a live host.

    so the question is, who wants to do what parts? 
  • here's a crazy idea. what if we went for truly temporary, at least initially. nanoparticles are simple enough to produce and it's now fairly well established on how to get them exactly where you need them before they burst and release whatever their load is. we could design a particle that would dump our test pigments where we need them and release it continually for a couple weeks. pigments would break down eventually but while they persist we can measure the test subject response to the pigment being there. if it's given in a measured dose it should only affect a small number of cones, just enough to add capability but not enough to throw off vision. then go from there
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