Please RT! I'm proud to tell everyone that the iPSC Neurodegenerative Disease Initiative #iNDI that I've been leading with @wardm50 is a physical entity as of today so let me explain why this is a huge deal: jax.org/jax-mice-and-s…
Why did we do this? Part of the idea for #iNDI came from experiments we did introducing mutations associated with age-dependent neurodegenerative diseases in the same background IPSC line, here sciencedirect.com/science/articl…
We then had the opportunity to expand this to look not just at all mutations across one disease, but across multiple diseases. If we could do that, we'd be able to understand relationships between mutations and diseases at a molecular level, not just symptoms
How did we do this, bearing in mind our plan grew from a few lines to many hundreds? The key things that worked were; to stay focussed on mutations with strong effect; to find the right partners to distribute the editing; and to pick a line and a method that was efficient
we have some of the rationale for initial line choice and editing improvements on Biorxiv here biorxiv.org/content/10.110… and here biorxiv.org/content/10.110… so people can replicate how we did things, if they so want to
And what do we expect to get from this? We hope this project will allow people to incorporate iPSC models into their research quickly and with less barriers. As part of the exploratory phase we get cells out to a postdoc in a lab who was able to get things up and running in weeks
...rather than having to spend months to years making lines and validating that they are truly isogenic. We were able to support this through #CARD, lead by @SingletonNeuro so that the cost to the end user is ~$350 plus shipping, much less than the 1000s we spent on our lines...
in other words, we did it once and hopefully well, so others don't need to spend their time and resources to do the same. We also hope that having consistent lines will help with reproducibility and that incorporating revertant lines, where we take the mutations out again..
will help with rigorous experimental design as it should account for any events away from the edited site. We also carefully checked the genome of the cells to try to avoid clones that might have randomly acquired some other unintended changes
Last Q: where is this going? Right now we have just one parent line and the first set of mutations available. In the next few months you'll see the number of lines start to increase so that it will end up being a serious resource so please watch this space
We are aware that first line is from a European male and have committed to generate additional series toadd diversity. We're working with @ASAP_Research and @cziscience to add specific variants and lines that have been identified as useful to their research community
This really has taken a village including @cornelisblauw @FlorianMerkle @BillSkarnes @narayan_pri @danramos117 @mike_nalls @FarazFaghri @_andrianyang and many twitterless folks in #iNDI
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