Synopsis of project aims
This project aims to develop a human-relevant microphysiological platform for studying liver-stage malaria infection and immune interception under physiologically realistic flow, tissue architecture, and extracellular matrix conditions. By integrating AI-designed, terminal-venule–inspired scaffolds with SLA bioprinting, macro- and microfluidic perfusion, and transgenically produced human collagen bio inks, the system is designed to recreate key features of the hepatic microenvironment encountered by Plasmodium sporozoites during early infection.
The platform is designed to overcome limitations of existing in-vitro models by enabling controlled delivery of sporozoites under physiologically relevant flow, real-time imaging of their characteristic screw-like gliding behavior, and direct quantification of how anti-circumsporozoite protein (anti-CSP) antibody binding alters parasite–matrix and parasite–cell interactions.
By reconstructing the terminal venule and sinusoidal microenvironment, this platform is designed to enable mechanistic dissection of where, when, and how anti-CSP antibodies exert protective effects during liver-stage infection, providing a foundation for future evaluation of vaccines, antibody therapies, and host–pathogen dynamics.
Specific aims
- Engineering Perfusable Liver Microenvironments that Recapitulate Sporozoite Entry Pathways
Design AI-generated, SLA-printed scaffolds inspired by human terminal venules to recreate sinusoidal geometry, and support sporozoite gliding, ECM interaction, and improve hepatocyte infection rate in vitro. - Human-Relevant Matrix Design Using Transgenic Human Collagen Bio inks
Fabricate optically clear, biochemically defined scaffolds using transgenically produced human collagen to support physiologically accurate parasite adhesion, migration, and antibody-mediated interference. - Quantifying the Impact of Anti-CSP Antibodies on Sporozoite Motility and Infection Efficiency
Measure how anti-CSP antibodies alter sporozoite stick-and-slip motility, tissue penetration, and productive hepatocyte invasion under flow using live imaging and infection readouts. - Comparative Analysis of Organoid Self-Organization versus Scaffold-Guided Infection Models
Evaluate infection dynamics in hepatocytes andGATA6-derived iPSC systems configured as free organoids versus cells or organoids embedded or seeded within engineered scaffolds. - Platform Integration for Vaccine and Therapeutic Evaluation
Use the system as a testbed to assess antibody potency, dosing, and mechanisms of protection in a human-relevant liver-stage context.
Project Team
- Azza Idris
- Ron Weiss
- Gilad Gomes
- Jennifer Suurbaar
- Erick Gross
- Roy Siegelmann
- Liam Aranda-Michel
- Tolga Durak