Case study – PROTAC picture from Michael Bond

The Yale Science Diplomats at Yale University have been using our S.P.A.R.K. online course to help train their members for the “Flipped Science Fair.” At the Flipped Science Fair, Yale researchers present their work to middle schoolers who both learn from the experience and get to judge the researchers’ posters.

In this blog post, Yale researcher Michael Bond shares his experiences working with our S.P.A.R.K. course and shows how he’s already putting our 5 strategies for the visual communication of science into action for the Flipped Science Fair.

The remainder of this post was written by Yale researcher Michael Bond

Creating a PROTAC picture

I set out to design a picture that would explain the mechanism of induced protein degradation by the PROteolysis Targeting Chimera (PROTAC) technology. PROTACs are two-headed (heterobifunctional) molecules that hijack a cell’s protein quality control (PQC) machinery to target disease proteins for degradation. Cellular PQC consists of two main parts:

1. Ubiquitin (Ub)  a small protein that can be linked to other proteins and marks them for degradation
2. E3 ligases – the proteins responsible for attaching Ub to diseased proteins. 

PROTACs function by simultaneously binding an E3 ligase and a protein of interest (POI) to be degraded. They form a ternary complex that allows the E3 ligase to tag the POI with Ub. Once Ub is added, the proteasome, a cellular trash can, can recognize and destroy the POI. My goal was to make a compelling figure that could explain ternary complex formation and PROTAC induced protein degradation to 8^th graders during Yale’s Flipped Science Fair.

In the first draft of my picture, I focused on highlighting the formation of the ternary complex and the ubiquitination of POIs by E3 ligases. I broke down each important step of PROTAC activity and used left to right orientation and a 3-step linear narrative of the POIs fate to convey the order of events. Underneath these events I put a schematic of a cell to show that the actions above occur within the cell, using the cell’s native PQC machinery. Using arrows, I show the progression of PROTAC treatment on proteins inside the cell and used a skull and crossbones to signify that, once the protein is destroyed, the cell dies. Although this picture conveys my message, it could be clearer, more aesthetically pleasing, and better emphasize the fact that the E3 ligase and POI are already inside cells, a common question asked by my 8^th grade audience.

Refining the PROTAC picture with the S.P.A.R.K. strategies

The S.P.A.R.K. strategies presented in Picture as Portal’s course helped me hone my message and present it more effectively to my young audience. For me, the “A” section of S.P.A.R.K., Access your Audience, was the most helpful section of the course. In this section we learned about letting go of literalism by considering the use of symbols or metaphors in place of more literal representations of scientific content. 

After watching the relevant video from the course, I decided to add pictures below each of the important players in the PROTAC process. The pictures give students real world objects that they can relate each protein to. For example, I represented the PROTAC molecule with a magnet because it “attracts’ the E3 ligase and the POI. The proteasome destroys the protein, so I added a trash can below it, a common analogy used in my field.

Another SPARK strategy I relied on in editing my original draft was the “R” section – Refine Relationships. This strategy helped me make my figure clearer and more aesthetically pleasing.

After learning about the elements of visual language covered in this section, I decided to add a box around the ternary complex inside my cell. Then I used dotted lines to show that I was zooming in on this ternary complex. Additionally, I put the cell schematic above the degradation events and made the cells larger to emphasize that everything I discuss is happening inside the cell. This will help the students see that the E3 ligase and the protein of interest are already inside the cell. Next, I added additional numbers and arrows to the “zoomed in” portion of the picture. These help organize the various events that take place during PROTAC-mediated degradation of the protein of interest.

I am grateful for the opportunity to have taken the Picture as Portal course, not only because it helped me redesign my Flipped Science Fair picture, but also because the lessons learned will ensure that my future scientific pictures are clear and concise. I am currently working on drafting a review for a peer-reviewed scientific journal. I will be thinking about the S.P.A.R.K. strategies as I design my figures for this publication. I would highly recommend S.P.A.R.K. to anyone who regularly makes complex figures in any field, especially science.

Sign up for S.P.A.R.K.!