Unravelling the role of structural genome plasticity in adaptation to nutrient starvation in Trypanosoma cruzi

Structural genome plasticity is increasingly recognized as a key aspect of trypanosomatid biology, enabling these parasites to survive in hostile environments. This is particularly relevant for Trypanosoma cruzi (T. cruzi), the etiological agent of Chagas disease, a neglected tropical disease with major disease burden and expanding global relevance. At both the population and single-cell levels, genome plasticity manifests through changes in chromosome copy number, segmental aneuploidy, and local copy number variations, yet its role in parasite adaptation remains poorly understood. This project aims to investigate the role of structural genome plasticity and genomic heterogeneity in the adaptation of T. cruzi to environmental changes. I will develop an in vitro model mimicking nutrient fluctuations to study the emergence, stability, and evolution of structural genome plasticity at the population level. I will then apply single-cell genomics to track structural genomic changes in individual parasites and assess how they shape parasite adaptation. Finally, I will examine the role of gene dosage in nutritional stress responses by identifying candidate genes and proteins, and validating their function using a CRISPR-Cas9 knockout library, linking genome plasticity to gene expression and parasite fitness. This study will provide new insights into T. cruzi genome plasticity and its role in adaptation, with broad implications for parasite evolution and therapeutic strategies.