Description

This two-page spread uses a molecular visualization to explore how pain becomes sensitized in inflammatory bowel disease (IBD). It focuses on how molecules released during cell damage interact with nociceptors, showing how chronic inflammation leads to an amplified pain response. The piece also highlights the cyclical nature of IBD pain, where ongoing inflammation activates nerves that, in turn, further drive inflammation. By visualizing this feedback loop, the spread helps explain why breaking the cycle is key to developing more effective pain-relief therapies.

Tools
ChimeraX, VMD, Z-Brush, Maya, and Illustrator

Type of Work
Assignment

Approach
2 page magazine spread

Client
Dr Derek Ng (University of Toronto)

Year
2025

Audience
General

Research and Ideation

The research for this piece focused on current literature around IBD, especially the mechanisms behind chronic pain. Through literature reviews and conversations with content experts, I worked to understand how ongoing inflammation drives pain sensitization at the molecular level. This included identifying which receptors and ion channels to show on nociceptors to support the signalling shown in the visualization.

At the same time, I explored several layout options, testing different ways to organize and layer information so the molecular interactions, narrative flow, and key takeaways could come through clearly in a two-page spread.

Production

The workflow started with cleaning and preparing PDB files in ChimeraX to make the molecular structures easier to work with. These were exported as OBJ files and brought into Maya, where the scene was built with careful attention to scale and spatial relationships. To add more organic detail, elements like neurons, epithelial cells, and ion channels were sculpted separately in ZBrush.

The final image was assembled and refined in Illustrator, bringing everything together into a cohesive piece that stays scientifically accurate while remaining clear and easy to read.

References

Background information, Page 1:

Impact of IBD in Canada Report - Impact of IBD in Canada Report - Crohn’s and Colitis Canada. Available from: https://crohnsandcolitis.ca/About-Us/Resources-Publications/Impact-of-IBD-Report

Szigethy E. Pain Management in Patients With Inflammatory Bowel Disease. Gastroenterol Hepatol (N Y). 2018 Jan;14(1):53. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC5824598/

Brierley SM, Linden DR. Neuroplasticity and dysfunction after gastrointestinal inflammation. Nature Reviews Gastroenterology & Hepatology 2014 11:10. 2014 Jul 8;11(10):611–27. Available from: https://www.nature.com/articles/nrgastro.2014.103

Grundy L, Erickson A, Brierley SM. Visceral Pain. Annu Rev Physiol. 2019 Feb 10;81(Volume 81, 2019):261–84. Available from: https://www.annualreviews.org/content/journals/10.1146/annurev-physiol-020518-114525

Signaling Cascade, Page 2:

Brierley SM, Linden DR. Neuroplasticity and dysfunction after gastrointestinal inflammation. Nature Reviews Gastroenterology & Hepatology 2014 11:10. 2014 Jul 8;11(10):611–27. Available from: https://www.nature.com/articles/nrgastro.2014.103

Molliver DC. G-Protein Coupled Receptors in Sensory Neuron Function and Pain. Encyclopedia of Neuroscience. 2009;1761–5. Available from: https://link.springer.com/rwe/10.1007/978-3-540-29678-2_2070

Gribkoff VK. The role of voltage-gated calcium channels in pain and nociception. Semin Cell Dev Biol. 2006 Oct 1;17(5):555–64. Available from: https://www.sciencedirect.com/science/article/abs/pii/S1084952106000991

Small Molecules Used:

ATP, sourced from PDB Database

RCSB PDB - ATP Ligand Summary Page. Available from: https://www.rcsb.org/ligand/ATP

5-HT, sourced from PubChem Serotonin | C10H12N2O | CID 5202 - PubChem. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/5202

Bradykinin, sourced from PDB database: ID 7F6H RCSB PDB - 7F6H: Cryo-EM structure of human bradykinin receptor BK2R in complex

Gq proteins and bradykinin. Available from: https://www.rcsb.org/structure/7F6H

Proteins Used:

Adenylate cyclase, sourced from UniProt: ID ADCY8. Currently trying to find how it binds to the Gα subunit.

ADCY8 - Adenylate cyclase type 8 - Homo sapiens (Human) | UniProtKB | UniProt. Available from: https://www.uniprot.org/uniprotkb/P40145/entry#structure

Nomura, R., Suzuki, S., Nishikawa, K., Suzuki, H., & Fujiyoshi, Y. (2025). Structural insights into human adenylyl cyclase 9 in complex with Gαs by Cryo-EM. Journal of Structural Biology, 217(3), 108223. https://doi.org/10.1016/j.jsb.2025.108223  RCSB PDB - 9U3R: Cryo-EM structure of human AC9. Available from: https://www.rcsb.org/structure/9U3R

Nav1.8, sourced from PBD database: ID 7WE4 and its phosphorylation sites for activation.

 RCSB PDB - 7WE4: Human Nav1.8 with A-803467, class I. Available from: https://www.rcsb.org/structure/7WE4

 Wu DF, Chandra D, McMahon T, Wang D, Dadgar J, Kharazia VN, et al. PKCε phosphorylation of the sodium channel NaV1.8 increases channel function and produces mechanical hyperalgesia in mice. J Clin Invest. 2012 Apr 2;122(4):1306–15. Available from: http://www.jci.org

Heinle JW, Dalessio S, Janicki P, Ouyang A, Vrana KE, Ruiz-Velasco V, et al. Insights into the voltage-gated sodium channel, NaV1.8, and its role in visceral pain perception. Front Pharmacol. 2024 May 23;15:1398409.

Bradykinin binding GPCR, sourced from PBD database: ID 7F6H.

RCSB PDB - 7MIY: Human N-type voltage-gated calcium channel Cav2.2 at 3.1 Angstrom resolution. Available from: https://www.rcsb.org/structure/7MIY Shen J, Zhang D, Fu Y, Chen A, Yang X, Zhang H. Cryo-EM structures of human bradykinin receptor-Gq proteins complexes. Nat Commun. 2022 Dec 1;13(1).

Geppetti P, Veldhuis NA, Lieu TM, Bunnett NW. G Protein-Coupled Receptors: Dynamic Machines for Signaling Pain and Itch. Neuron. 2015 Nov 18; 88(4):635–49. Available from: https://www.sciencedirect.com/science/article/pii/S0896627315009800#fig5

CaV2.2, sourced from PBD Database: ID 7MIY and its phosphorylation sites for activation.

RCSB PDB - 7MIY: Human N-type voltage-gated calcium channel Cav2.2 at 3.1 Angstrom resolution. Available from: https://www.rcsb.org/structure/7MIY

Lacinova L, Mallmann RT, Jurkovičová-Tarabová B, Klugbauer N. Modulation of voltage-gated CaV2.2 Ca2+ channels by newly identified interaction partners. Channels. 2020 Jan 1;14(1):380. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC7567506/

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