Data-driven agent-based modelling of Trypanosoma collective behaviour

• Applicant: Professorin Dr. Sabine Fischer
• Subject Area: Bioinformatics and Theoretical Biology ; Biophysics ; Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 492009575

The unicellular parasite Trypanosoma brucei exhibits swarming with linear alignment in the tsetse fly midgut. Colonies of the insect-form of the parasite show radial projections in in vitro social motility assays on agarose gel. Quantitative characterisations of the collective behaviour are available, but the underlying mechanisms as well as the link to the in vivo situation require further investigations. We address these questions by data-driven development of an agent-based model for collective behaviour derived from the Vicsek model (Vicsek et al. 1995). Considering physical as well as chemical agent-agent and agent-boundary interactions, we test our main hypothesis that collective motion of trypanosomes can be reproduced by a combination of negative auto-chemotaxis and parasite alignment at the boundary. A computationally efficient implementation of the model in the programming language Julia allows simulations for agent numbers comparable to the number of parasites in the experiments. Hence, a direct, quantitative comparison of the simulation results to experimental data is feasible. We consider both data from the literature as well as from other projects in the Priority Programme. Collaboration with experimental projects allows assessing the biological relevance. The model quality in terms of the approximation of physical pronciples is tested through interaction with projects that develop detailed hydrodynamic simulations of the parasite. Having established an appropriate computational representation of the quasi two-dimensional in vitro assay, we transfer our agents to three spatial dimensions to establish a link to the in vivo situation. In particular, we consider a channel with a flow field as well as constrictions and obstacles to represent the fly gut. Analysis of our model in this setting provides insight into the sensitivity of the collective behaviour of trypanosomes to changes of the environment geometry. During the development of the agent-based model, we place an emphasis on generality. To form the basis for a wider adoption of our model, we have identified three proposed projects in the Priority Programme that investigate the movement patterns and interactions of large groups of individuals, namely Heligmosomoides poligyrus in the small intestine, Giardia muris in the small intestine and Plasmodium falciparum tubulin dimers in liquid droplets. Testing our modelling approach on these systems helps to further our understanding of general physical concepts in parasitology. Our project contributes to a more detailed understanding of Trypanosoma locomotion and the physics of the interaction with boundaries in the microenvironment. In addition, it promotes similar studies in other parasitic systems.

• DFG Programme: Priority Programmes
• Subproject of: SPP 2332: Physics of Parasitism