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Amblyostatin-1, the first salivary cystatin from Amblyomma sculptum: biochemical targets, biological activity and potential use as a vaccine and immunobiological

Grant number: 23/07831-7
Support Opportunities:Scholarships abroad - Research Internship - Master's degree
Effective date (Start): October 01, 2023
Effective date (End): March 31, 2024
Field of knowledge:Biological Sciences - Parasitology - Entomology and Malacology of Parasites and Vectors
Principal Investigator:Anderson de Sá Nunes
Grantee:Wilson Santos Molari
Supervisor: Michail Kotsyfakis
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: Czech Academy of Sciences (CAS), Czech Republic  
Associated to the scholarship:22/07724-3 - Amblyostatin-1, the first salivary cystatin from Amblyomma sculptum: biochemical targets, biological activity and potential use as a vaccine and immunobiological., BP.MS

Abstract

Amblyomma spp. include the ticks with the largest abundance and distribution in Brazil. More specifically, Amblyomma sculptum, a species endemic to the southeast region, is an important parasite of several vertebrates including humans. These ticks are of clinical relevance due to the transmission of pathogens such as Rickettsia rickettsii, the causative agent of Brazilian spotted fever, a disease with a high lethality rate. The transmission is facilitated by the bioactive molecules present in tick saliva which are secreted during blood feeding. Some of these molecules display modulatory activities on the host's hemostatic and immune responses at the cellular and biochemical levels to ensure that tick feeding successfully occurs and to prevent vertebrate rejection. These functions reveal the potential use of these molecules for the development of therapies to treat clinical conditions characterized by exacerbation of immune responses. Knowing the biological activities of salivary protease inhibitors from other tick species, the present work, supported by FAPESP (process # 2022/07724-3), proposes to characterize Amblyostatin-1, the first cystatin of A. sculptum saliva, whose transcript was recently identified in the sialotranscriptome of the species. In order to complement the results achieved in the first year of the project, we established a collaboration with Dr. Michalis Kotsyfakis, a researcher from the Institute of Parasitology, Biology Centre, Czech Academy of Sciences (Czech Republic) with strong expertise in biochemistry, molecular biology, and 3D protein analysis. Thus, we are applying for a fellowship from the Research Internship Abroad Program (BEPE) to support us during a 6-month staying at the Institution. We intend to express high amounts of the recombinant protein, determine the three-dimensional structure of this inhibitor, and determine the structural and biochemical targets of the molecule. (AU)

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