I have decided to start brew down some of the advice I have been giving on switch labs in the Switch Lab Guide and the later shorter version of the former: Different Types of Switches. Here it comes:
These are pointers towards what I think will work well for switch labs, from what data I have seen so far.
I wish you too, to watch out for how switches behave. What makes them work, what makes them move?
Being a citizen scientist
As encouragement, I want to share a fine article I found on being a citizen scientist. Enjoy!
Its still very much a work in progress. But the aim is to go more into details of how solve a switch lab puzzle in practice. I will add more pictures along the way. I just put it up now so it can be of help with the current round.
Omei has already made a fine Switch Lab Tutorial puzzle:
I have started to collect some resources on microRNA and put them in a presentation. It is very much still a work in progress, but I’m putting it up in the hope it may still be of some help for this round.
we need to be able to show a screen shot of our specs in chat so we can compare our data together . One could explain shape data and melting dot plot data to inquiring individuals if this were an option. Thanks!
This is thought as a helper for the [A]/[B] lab and future labs of that kind.
I think we already have a lot of the math tools needed, to make an increase of concentration of one microRNA over another. Just to mention a few things that can likely increase the presence and binding of one microRNA over the other:
Position of the microRNA in relation to the MS2 - before and after
MS2 gates - now they should come in really handy as a one way brake
MS2 turnoffs - and them being before and after the MS2
MicroRNA catching dangling stretches - and their length - also in relation to each other
How much of the microRNA that is targeted - length in total
Basically I think we can totally exploit even those things that have weighed down in past microRNA labs and slowed the switching, as the microRNA labs we have had so far have not had big problems with getting a good fold change. So things that in other labs have hurt the switching ability - like MS2 gates are now fair game for pushing the concentration of one microRNA up over the other. Especially since both the turnoff and turnoff microRNA labs have shown a good tolerance for MS2 gates.
My intro is not finished, but since I think it what is there may already be of help, I put it up. Bear with the mess - work in progress.
Attaching the oligo’s to the main RNA sequence has started to appear straight forward, but where to place them and how they affect the MS2 hairpin still seems like an artform to me:)
Here is an illustration of another route to get to a solve. I have called this design route B before A. Here I take advantage of that MS2 and TB B are directly complementary and use it for MS2 turnoff in state 1, where both needs to be gone.
Notice that I in both illustrations have put the static stem first. Our earlier microRNA lab data has shown that the microRNA mainly prefer to land in the late end of the RNA sequence (3’) in turnon labs, which R2 is.
Turnon and turnoff is taking the perspective of the MS2. Here MS2 is needed to get turn on in the later state = hence turnon lab. (Edited)">here.
A while back I put up an unfinished guide up as for helping with lab. The guide is still unfinished, but since a part of it deals with labs with inputs, I put it here as well.