Living Circuits: A CRISPR NOR Gate

Living Circuit: CRISPR NOR Gates Tracy Xiang
A Scientific American Infographic spread mockup depicting the constructing of a CRISPR circuit. Client: Prof. Derek Ng. Part of the molecular visualization coursework (MSC2020). Media: Maxon Cinema 4D with epmv plugin (molecular models retrieval and rendering), Adobe Photoshop (compositing), Adobe Illustrator (textual elements and icons).

Process Work:

We were asked to create a two-page infographic spread for a popular science magazine, on any molecular biology hot topic. I met some very smart people from the 2017 Toronto iGem team. Their project last year was about fine-tuning the CRISPR-Cas9 system via a light-sensitive switch, where I first learned about turning this molecular network into logical functional units. During the research phase, I read about how the largest living circuits were constructed in yeast cells, and how one single type of logic gate can be rearranged to compute other logic functions (functional completeness).

Screen Shot 2018-07-18 at 9.10.54 PM
Fitst Draft Sketch: The CRISPR circuit

My early draft focused more on the elements of the circuit –– for example, to complete the circuit, the circuit output, a strand of guide RNA, must remain inside the nucleus. By nature, RNA wants to exit the nucleus. How do we keep that RNA inside the nucleus? well, you flank the RNA export signal with two self-cleaving ribozymes. As the ribozymes cut themselves free from the guide RNA, they take the export signals with them leaving the guide RNA to roam inside the nucleus until it’s picked up by its Cas9 counterpart.

 

CRISPR Circuit draft
4th draft of the CRISPR circuit infographic

––– Spoilers, the ribozyme part did not make it into the final draft (that beautiful ominous looking polymerase also didn’t make it). After a few rounds of peer review, my classmates and instructor pointed out that what’s missing from the narrative was the application of the technology. The focus of this piece is not the molecular construct, it’s the possibility it inspires. Making a molecule inside a cell has become pretty standard. But with advanced synthetic tools like CRISPR, what if we could add some logic to this production process? What if we could say, only make that molecule on specific situations? How about fitting the gene circuit in the context of a cancer patient? The gene circuit detects cancer using some logic; such as, am I in a cancer cell, or am I in a normal cell? If the cell is in a cancer cell, we don’t make the molecule. if we are in a normal cell, we will make that molecule that kills the cell. 

Thinking of a scenario got me very excited. Inspired the initial 8-bit font choice, I changed all the schematic elements into 8-bit representations after looking up tutorials on creating pixel art (WARNING, this is addictive).

8-bit polymerase, Cas9, cancer cell and normal cell

The graphic itself is a composite of several renders. The models are retrieved from the protein data bank by the epmv plugin, and rendered using Maxon Cinema 4D. The long DNA strand is taken from DNA strands associated with the protein themselves, and short segments I built using epmv.

Early drafts and composites for the CRISPR circuit
Early drafts and composites for the CRISPR circuit and CRISPR NOR gate

If you have a molecular biology or biochemistry background, Derek’s molecular visualization course albeit stressful, will definitely be the highlight of your semester. The amount of tools you learn within 5 weeks is INSANE.

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