Alvite Gaye, Gabriela

Research interests

For decades, our group has focused on the search and study of key molecules to combat Cyst echinococcosis, a global zoonosis considered one of the twenty neglected tropical diseases by the WHO. The larval form of Echinococcus granulosus s.l. (cestode platyhelminth) is the cause of this parasitic infection, which constitutes a public health problem and causes economic losses, affecting humans, livestock, and the environment. There is a need for new treatments due to the development of parasitic resistance, among other causes. Initially, my research activity has focused on studying the structure and function of fatty acid-binding proteins (FABPs) from cestodes, which could be key proteins in these organisms since they are unable to synthesize fatty acids de novo. FABPs could participate in the regulation of gene expression and lipid metabolism. We have characterized EgFABP1 (EgFABP with higher expression in protoscolex larvae), determining its preference for long-chain unsaturated fatty acids and its nuclear localization, among other aspects. Recently, I have focused on deciphering the nuclear function of EgFABP1, searching for nuclear receptors (NRs) that can interact with it. Thus, we have identified four 2DBD NRs in E. granulosus: Eg2DBDα, Eg2DBDα.1, Eg2DBDβ, and Eg2DBDɣ. These NRs are interesting because, in addition to possessing two DNA-binding domains, members of the 2DBD subfamily are not present in the parasite's hosts. NRs are transcriptional regulators of diverse biological processes, and NRs from parasitic helminths are considered potential targets for anthelmintic drugs since they could modulate signaling triggered by exogenous lipophilic ligands. We have initiated a new line of research focused on the structure and function of Eg2DBDs. We have advanced our study of Eg2DBDα.1 (Eg2DBDα isoform), generating a 3D model of the entire protein, determining its preference for binding long chain and unsaturated fatty acids (similar to EgFABP1), that it forms homodimers, and that the serum of the intermediate host (bovine) stimulates dimerization, suggesting a possible host-parasite communication. Furthermore, we have shown that Eg2DBDɣ is poorly or not expressed, while Eg2DBDα and Eg2DBDβ are the 2DBD-NRs with the highest levels of expression in protoscoleces. We are currently analyzing the localization of Eg2DBDs at this stage. Based on our results and the proven FABP-NR interaction in vertebrates, we speculate that EgFABP1 could transfer its ligand to Eg2DBDs, enabling them to regulate gene expression of their target genes in E. granulosus protoscolex cells. In this context, we propose to study the interaction capacity of EgFABP1 with Eg2DBDs and identify the ligands, binding regions in the genome, and target genes of these NRs. In this way we seek to provide new knowledge that contributes to the elucidation of possible signal transduction and gene expression regulation pathways by investigating the biological functions of Eg2DBDs and EgFABP1, laying the foundations for the generation of new therapeutic candidates to combat Cystic echinococcosis.