Our lab uses state-of-the-art strategies of reverse genetics to identify and functionally characterize genes involved in essential processes in the life cycle of the human pathogen Trypanosoma cruzi. Our ultimate goal is to investigate the role of essential genes that can be further validated as potential drug targets in this parasite, the causative agent of Chagas disease
To achieve this goal, the study of essential biological processes and the identification of key regulatory proteins in T. cruzi life cycle are crucial. In humans, protein kinases (PKs) have been the focus of drug discovery efforts due to their relevance in cancer, diabetes, inflammation, and neurodegeneration. Kinases represent almost 30% of the “druggable human genome,” and approximately 20 PKs in the human kinome are targets of FDA-approved inhibitors. Approximately 2% of the T. cruzi genome encodes protein kinases, suggesting a major regulatory role in controlling parasite development and function. Therefore, PKs represent a rich family of potential biological targets to pursuit anti-T. cruzi agents. We are interested in investigating the role of protein kinases, establishing their importance in survival, differentiation and infection ability of T. cruzi.
Another promising source of specific targets for antiparasitic interventions is cytokinesis, a cellular process considered the final step in cell division. Cytokinesis, a poorly understood process in T. cruzi, is crucial because its failure practically terminates all previous mitotic events, causing polyploidy and other subsequent defects in mitosis and chromosomal stability, which in unicellular organisms leads to cell arrest or cell death. Cytokineses in T. cruzi is regulated by mechanisms that are different to those in its human host, involving trypanosome-specific proteins that interact with evolutionarily conserved regulators.
Taking advantage of our extensive experience in the genetic manipulation of T. cruzi, we use CRISPR/Cas9-mediated genome editing strategies to study protein kinases and cytokinesis-related genes in this protozoan parasite.