CRISPieR: Re-engineering CRISPR-Cas9 with functional applications in eukaryotic systems

Published: September 28, 2015   |   Read time:

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The CRISPR-Cas9 system had been making headlines for the past few years, and its possible applications in synthetic/systems biology are pretty exciting. The iGEM team had been interested in this topic for a few years, at this point, so we decided to face some of the issues surrounding CRISPR head on, to see what developments could be made in the area.

I won’t discuss the specifics in great depth, since I think we did a pretty good job explaining everything on our wiki1 (unfortunately it looks like javascript has been disabled on the back-end, so the site isn’t working properly). But the main ideas behind the project were:

  1. Simplify the selection and replacement of guide RNAs
  2. Increase the flexibility of binding sequences by modifying the Cas9 protein to be less reliant on its PAM sequence
  3. Test out these improvements by introducing as CRISPR-based anti-viral mechanism in plants for Cauliflower Mosaic Virus

This was my most involved year in the team, as I took on the Project Director role. It was exciting being essentially a mini-principal investigator for the group and getting to see the logistical side of things in how research groups run.

I did a ton of different things:

  • project ideation
  • interviewing new team candidates
  • managing finances
  • leading math modelling tutorials
  • setting up computational resources for protein folding software
  • organizing meetings with our advisors
  • website design for our project wiki
  • writing and delivering financial proposals
  • running and organizing groups meetings
  • basic math modelling (when I had time)
  • managing lots of other logistics for the team

I also ended up taking my own mini-project and wrote a critique of iGEM and how it functions2. My main issue stemmed from the fact that is was so expensive to actually run the team, and that I had participated in other university teams that didn’t require nearly the same scope of resources to.

The critique made a little bit of noise, as Randy Rettburg (one of the iGEM founders) came to talk to me about my article. That was unexpected, but it honestly was quite a nice conversation. Like I mention in the “Post-Jamboree Update”, he and I discussed some logistics of the competition and how it works, and the amount of personal investment Randy had made in iGEM when it was in danger of going bankrupt.

I don’t currently stand by everything that I said in that critique, but I understand why I said what I did, and I think there are still some elements of truth in there.

Summary

All in all, 2015 was a very intense and difficult year for me doing iGEM, but I learned an incredible amount about research, managing teams and people, properly expressing criticism, and a little bit of modelling and wet-lab work along the way.

That was the most successful year our team had at the competition, and we were proud of that. There were ~ 40 people in total who put in a ton of time, effort, and energy into our work, and though there were many highs and lows, I sincerely appreciate everything that happened, and the lessons learned.

If you want a full description of the team’s work, it can be found on the Waterloo iGEM’s 2015 project wiki1.

References