| Grant number: | 13/20715-4 |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| Start date: | March 01, 2014 |
| End date: | January 31, 2020 |
| Field of knowledge: | Biological Sciences - Biochemistry - Molecular Biology |
| Principal Investigator: | Ana Paula Ulian de Araujo |
| Grantee: | Ana Eliza Zeraik |
| Host Institution: | Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil |
| Associated research grant: | 14/15546-1 - Septins: comparative studies and the correlation between structure and function, AP.TEM |
| Associated scholarship(s): | 16/12505-8 - Characterization of the calcium release-activated (CRAC) channel in the human pathogen Schistosoma mansoni through the study of its components STIM and ORAI proteins, BE.EP.PD |
Abstract Septins belong to the GTPase family of proteins and are involved in a variety of cellular functions mainly related to membrane remodeling events. These proteins have been described in several organisms and the number of septins in each organism varies from one (in some species of algae) to 13 (in humans) and frequently form hetero-oligomeric complexes that assemble into filaments. We have recently described four genes encoding septins in Schistosoma mansoni (Zeraik et al. 2013, paper submitted), one of the major causative agents of schistosomiasis. In vivo experiments recently performed in our group with forchlorfenuron (FCF), a drug that affects the dynamics of septin filaments have resulted in a reversible paralysis phenotype in adult worms and cercariae of S. mansoni, indicating that these proteins might be involved in muscle contraction. Recent study (Sharma et al. 2013) revealed that septins are essential components in the activation of a calcium pathway, SOCE (Store-operated calcium entry) and it is known that this ion is essential for muscle contraction. Furthermore, a report have shown that the incubation of S. mansoni adult worms in medium containing a high Mg2+:Ca2+ ratio promoted the inhibition of Ca2+ uptake and a reversible paralysis phenotype (Blair el al. 1992) similar to that observed in our experiments. These observations have lead us to propose the hypothesis in which the change in septin dynamics caused by FCF could affect this calcium channel in S. mansoni, decreasing the Ca2+ entry in the cells as observed in mammalian cells. Therefore, this project focus on the study of FCF effects in S. mansoni, aiming the establishment of correlations between the reversible paralysis caused by this compound and the impairment of the calcium channel dependent on septins. SOCE is an evolutionary conserved pathway and not yet studied in S. mansoni, what makes this calcium channel also pharmacologically attractive, since praziquantel, the main drug against schistosomiasis, affects the calcium homeostase in the cells and promotes paralysis in adult worms, stimulating us to investigate FCF and its derivatives as potential drugs against this disease. The study of this system might provide the establishment of functional relationships among S. mansoni septins and analogous septin complexes of other organisms, contributing to elucidate the function of this family of proteins. | |
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