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Selective Membrane-Binding Peptides: Computational Design and Experimental Validation for Advanced Biotechnological Applications

Project description

Insight into lipid-binding peptides

Protein interactions with membranes are important for various biological processes such as cellular signalling. In addition, membrane-binding peptides are promising tools for antimicrobial therapies, biosensing and the purification of extracellular vesicles. To be effective in biotechnology, however, these peptides must bind selectively to specific membrane lipids. With the support of the Marie Skłodowska-Curie Actions programme, the SELPEP project will focus on a specific peptide that targets cardiolipin, a lipid found only in mitochondria and bacterial membranes. Researchers will study how peptide sequence variations affect membrane binding. Project findings will help them understand the fundamental principles of protein-lipid interactions and fuel future research in targeted drug delivery and diagnostics.

Objective

Membrane-binding peptides have significant potential applications, such as antimicrobials, biosensors and in the purification of extracellular vesicles. However, to ensure the effective implementation of these peptides in biotechnological applications, it is essential to prioritize their selectivity. The Opi1 peptide has previously been shown to exhibit a high affinity for phosphatidic acid (PA)-containing membranes. Given the analogous structure of cardiolipin (CL), this proposal posits that it may be possible to develop an Opi1 variant that interacts selectively with CL-containing membranes with diverse CL proportions. Cardiolipin (CL) is exclusively found in the inner membrane of mitochondria and bacteria, making this phospholipid an interesting candidate for the design of selective peptides. The project will entail the implementation of in silico mutations of the Opi1 sequence, in order to identify novel sequences with different affinity to model membranes. The optimization and analysis of peptide-membrane interactions will be conducted through the use of atomic-resolution molecular simulations, alchemical transformations, and experimental biophysical techniques, such as liposome flotation methods and quartz crystal microbalance assay. This interdisciplinary project integrates biology, physics, and chemistry, leveraging advanced computational and experimental techniques to achieve the objectives. The interdisciplinary integration ensures robust outcomes, with potential applications in targeted drug delivery, and diagnostics, ultimately advancing our understanding of peptide-membrane interactions.

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Topic(s)

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

Masarykova univerzita
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 207 758,16
Address
Zerotinovo namesti 9
601 77 Brno
Czechia

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Region
Česko Jihovýchod Jihomoravský kraj
Activity type
Higher or Secondary Education Establishments
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Total cost

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