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Bioinspired Coacervates Based on Bioactive Peptides Derived from Viral Proteomes

Grant number: 23/18385-8
Support Opportunities:Scholarships abroad - Research
Effective date (Start): May 01, 2024
Effective date (End): February 28, 2025
Field of knowledge:Biological Sciences - Biophysics - Molecular Biophysics
Principal Investigator:Emerson Rodrigo da Silva
Grantee:Emerson Rodrigo da Silva
Host Investigator: Guillaume Tresset
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Research place: Laboratoire de Physique des Solides (LPS), France  

Abstract

Biomolecular condensates are a common phenomenon in biological matter, playing a crucial role in proper cellular functioning. This phenomenon appears when spontaneous phase separation occurs in equilibrium in a liquid environment, typically triggered by the mixing of biomolecules with opposite charges in aqueous medium. In addition, they may serve as an intermediate step in the formation of micro structured scaffolds such as hydrogels. These condensates are also referred to as "coacervates", and they hold great potential in biophysical research, where they can serve as models for studying membrane-less organelles in synthetic biology, as well as for the fabrication of molecular carriers capable of delivering therapeutic compounds. In this project, we will focus on the formulation and characterization of new coacervates resulting from the association of bioactive peptides (cell-penetrating, anti-inflammatory, extracellular matrix) derived from viral proteomes in association with nucleic acid sequences. The main scientific objective and technological challenge of our proposal consist in obtaining thermodynamically stable phases under conditions typically found in the biological environment. To overcome this challenge, we propose modifying peptide sequences derived either from surface antigen proteins of hepatitis B virus (HBV) or the spike protein of SARS-CoV-2, whose cell-penetrating capabilities have already been identified by our group. Inspired by a strategy recently developed by partners in France, we will introduce modifications to these bioactive sequences by adding fatty acid chains to their structure. Structural characterizations of these condensates will be conducted using advanced techniques, including synchrotron small-angle X-ray scattering, cryogenic electron microscopy, and atomic force microscopy. Functional evaluations of these condensates will be carried out in cell culture, using fluorescence microscopy and flow cytometry techniques. The project emphasizes international cooperation with a world-class center in research at the physics/biology interface and represents a unique opportunity for exchanges involving Brazilian students and researchers, thereby elevating the status of our research group.

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