Massive parallel de novo design of sensing nanopores
PoreMADNeSS aims to innovate transmembrane β-barrel design for nanopore sensors using computational methods and machine learning to enhance sensing capabilities for new analytes.
Projectdetails
Introduction
Proteins embedded in membranes play key roles in maintaining cell integrity, homeostasis, and communication. Emerging technologies (nanopore sequencing, synthetic cells, etc.) imitate biological systems and repurpose membrane proteins for the transport and sensing of new analytes through synthetic membranes. These applications have fueled the demand for (synthetic) membrane proteins with properties and functions not observed in nature.
Current Challenges
Structure-based computational protein design is revolutionizing many aspects of biotechnology but has almost exclusively focused on protein folding in water. The aim of PoreMADNeSS is to develop innovative strategies to enable the design of transmembrane β-barrels (TMBs), a class of membrane proteins with excellent properties to act as nanopore sensors.
Research Objectives
Using multidisciplinary approaches, we will address basic biophysical knowledge gaps that currently limit TMB design. The design of TMB folding in synthetic membranes gives access to a wealth of TMB sequences and structures not sampled by nature because of constraints associated with biogenesis and with the composition of biomembranes.
Methodology
We propose a combination of massive parallel de novo design and adaptive machine learning to explore this unknown TMB space, to gain crucial insight into the determinants of TMB folding, and to develop robust design methods.
Proof-of-Concept
As a proof-of-concept, PoreMADNeSS will focus on the design of steroid sensing nanopores. Our strategy is to design a cortisol binding site across the transmembrane channel, which would act as the reading head for single molecule fingerprinting.
Previous Work
My lab was the first to demonstrate the feasibility of TMB design and has established a design pipeline from computation to electrophysiology and biochemical characterization.
Expected Impact
This project has all the components to translate into transformative advances in nanopore sensing and sequencing by providing the nanopore R&D community with accurate and innovative computational design methodologies.
Financiële details & Tijdlijn
Financiële details
Subsidiebedrag | € 1.499.250 |
Totale projectbegroting | € 1.831.287 |
Tijdlijn
Startdatum | 1-4-2024 |
Einddatum | 31-3-2029 |
Subsidiejaar | 2024 |
Partners & Locaties
Projectpartners
- VIB VZWpenvoerder
Land(en)
Vergelijkbare projecten binnen European Research Council
Project | Regeling | Bedrag | Jaar | Actie |
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Bringing Nanospace to Life by Adapting Pore Environments to Chemical ComplexityLIVINGPORE aims to develop synthetic porous materials with programmable pore environments for enhanced structural and functional responses, mimicking biological systems for innovative applications. | ERC Consolid... | € 1.998.974 | 2023 | Details |
Bioinspired Transmembrane NanomachinesMembraneMachines aims to design and build innovative transmembrane nanomachines using DNA technology to harness electrochemical gradients for molecular synthesis and active transport. | ERC Starting... | € 1.812.400 | 2024 | Details |
Membrane Micro-CompartmentsThe project aims to develop a system for in situ structural analysis of membrane proteins to enhance drug interaction studies and facilitate their commercialization in the pharmaceutical industry. | ERC Proof of... | € 150.000 | 2024 | Details |
Time-resolved imaging of membrane transporter dynamics under physiological ionic gradientsThe project aims to develop a microfluidic platform for high-resolution, time-resolved structural studies of membrane proteins under physiological conditions to enhance drug targeting and understanding of cellular functions. | ERC Synergy ... | € 11.178.784 | 2024 | Details |
Protein function regulation through inserts for response to biological, chemical and physical signalsThis project aims to develop a modular platform for engineering proteins to sense and respond to diverse signals, enhancing their functionality for innovative biomedical applications. | ERC Advanced... | € 2.500.000 | 2024 | Details |
Bringing Nanospace to Life by Adapting Pore Environments to Chemical Complexity
LIVINGPORE aims to develop synthetic porous materials with programmable pore environments for enhanced structural and functional responses, mimicking biological systems for innovative applications.
Bioinspired Transmembrane Nanomachines
MembraneMachines aims to design and build innovative transmembrane nanomachines using DNA technology to harness electrochemical gradients for molecular synthesis and active transport.
Membrane Micro-Compartments
The project aims to develop a system for in situ structural analysis of membrane proteins to enhance drug interaction studies and facilitate their commercialization in the pharmaceutical industry.
Time-resolved imaging of membrane transporter dynamics under physiological ionic gradients
The project aims to develop a microfluidic platform for high-resolution, time-resolved structural studies of membrane proteins under physiological conditions to enhance drug targeting and understanding of cellular functions.
Protein function regulation through inserts for response to biological, chemical and physical signals
This project aims to develop a modular platform for engineering proteins to sense and respond to diverse signals, enhancing their functionality for innovative biomedical applications.
Vergelijkbare projecten uit andere regelingen
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Computation driven development of novel vivo-like-DNA-nanotransducers for biomolecules structure identificationThis project aims to develop DNA-nanotransducers for real-time detection and analysis of conformational changes in biomolecules, enhancing understanding of molecular dynamics and aiding drug discovery. | EIC Pathfinder | € 3.000.418 | 2022 | Details |
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Haalbaarheidsonderzoek: portable nanopore device voor de identificatie van eiwitten en biomarkers.
Portal Biotech ontwikkelt een draagbaar analysetoestel op basis van nanopore technologie om real-time eiwitmetingen mogelijk te maken, wat de diagnostiek revolutionair verandert.
Haalbaarheidsonderzoek analyse-apparaat voor volledige en gevouwen eiwitten
Portal Biotech ontwikkelt een innovatieve nanopore-technologie voor het meten van volledige eiwitten, met als doel de diagnostiek te revolutioneren en klinische beslissingen te verbeteren.
Computation driven development of novel vivo-like-DNA-nanotransducers for biomolecules structure identification
This project aims to develop DNA-nanotransducers for real-time detection and analysis of conformational changes in biomolecules, enhancing understanding of molecular dynamics and aiding drug discovery.
BIOmimetic selective extraction MEMbranes
BIOMEM aims to create energy-efficient biomimetic membranes using biological transport proteins for selective extraction of valuable compounds and pollutants from water.