PARA-SIGHT
Trypanosoma brucei

Project Overview

Immersive animation showcasing the infection mechanism of the Trypanosoma brucei parasite, responsible for causing African sleeping sickness. Developed as a public engagement tool in collaboration with WCIP and designed and developed with one of the main authors of the paper, 'Generation of neuroinflammation in human African trypanosomiasis', Jean Rodgers. The animation was strategically deployed for public engagement. Its purpose was to elucidate complex scientific concepts to diverse audiences.

Scientific paper:https://doi.org/10.1212/NXI.0000000000000610

Trypanosoma brucei movement

Intracellular Matrix

Within the brain, capillaries are encompassed by the blood-brain barrier (BBB), which holds a pivotal function inupholding brain health and function.The blood-brain barrier is higly selective, effectively blocking the entry of pathogens and detrimental substances present in the bloodstream. The Blood Brain Barrier consists of Pericytes, Endothelial Cells, Tight Junctions, andAstrocytic end feet attachements. These junctions are created by assemblies of transmembrane proteins that connect neighboring cells. These arrangements of junctions form networks across the endothelial cell surface, restricting permeability.

As Human african trypanosomiasis advances, lymphocytes and parasites migrate from postcapillary venules acrossthe Blood Brain Barrier to enter the brain parenchyma. The production of the cysteine protease, brucipain, by the parasites increases their ability to migrate acrossthe endothelial cell layer of the blood brain barrier. After activation in the peripheral compartment, T-cell migration through the endothelial cell layer of the blood brain barrier can occur using both paracellular and transcellular routes. On breaching the endothelial celllayer, both T-cells and trypanosomes must penetrate the endothelial basement membrane. This is dependent on the laminin subtypes present. Areas where alpha4 laminin predominates allow transmigration while alpha5 laminin-rich regions inhibit crossing into the perivascular space.

laminin alpha 5
laminin alpha 4

While progress has been made inunderstanding human African trypanosomiasis, there are still many unansweredquestions. A deeper grasp of the disease's mechanisms will enhance treatmentand therapy options.  Continued researchis essential to unravel this complex infection. If you're looking for moredetails or wish to contribute to our mission, please feel free to reach out tothe welcome center for Integrative Parasitology.