Studies on voltage-gated ion channels, recombinant expression and determination of the molecular structure of toxins of the endoparasitoid Cotesia flavipes (Hymenoptera: Braconidae)

• Grant number: 25/00719-2
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: November 01, 2025
• End date: June 30, 2026
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Suely Vilela
• Grantee: Ciro Pedro Guidotti Pinto
• Supervisor: Glenn Frederick King
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of Queensland, Brisbane (UQ), Australia
• Associated to the scholarship: 22/12499-9 - Antitumoral activity of toxins from the endoparasitoid Cotesia flavipes (Hymenoptera: Braconidae), BP.PD

Abstract

Arthropod venoms are composed of a wide range of toxins with varied pharmacological properties. Endoparasitoids use several of these regulatory molecules to transform their hosts into a suitable environment for the development of their offspring. These regulatory molecules are still little explored for human health therapy, but studies are already discussing their biotechnological potential. This project aims to explore the action of toxins identified from teratocytes (cells derived from embryos) and venom of the endoparasitoid Cotesia flavipes (Hymenoptera: Braconidae) in voltage-gated ion channels, their heterologous expression and elucidate their molecular structure by nuclear magnetic resonance (NMR). By a robust proteotranscriptomic approach, we described the venom and teratocytes molecules of the endoparasitoid C. flavipes. Using this database, based on computational tool algorithms, six toxins were selected to be tested for their antitumor activity against different tumor cell lines. Among the results obtained, we found that the toxins Cft-IV and H-BCTX-Cf4 showed cytotoxic activity by secondary necrosis mechanism in an acute monocytic leukemia (THP-1) cell line, and due to the nature of the peptide, it is likely to be active in voltage-gated ion channels. In addition, we have established a recombinant expression flux for peptide production in Escherichia coli, but improvements can increase the productivity of the molecules. This proposal aims to carry out part of the postdoctoral project approved by FAPESP process nº 2022/12499-9 with an internationally recognized toxinology group, forming important partnerships for future projects and allowing the transfer of technology to our unit in Brazil.