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Massive parallel de novo design of sensing nanopores

Objective

Proteins embedded in membranes play key roles in maintaining cell integrity, homeostasis and communication. Emerging technologies (nanopore sequencing, synthetic cells, …) imitate biological systems and repurpose membrane protein for the transport and sensing of new analytes through synthetic membranes. These applications have fuelled the demand for (synthetic) membrane proteins with properties and functions not observed in nature. 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. 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. 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. 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. My lab was first to demonstrate the feasibility of TMB design and has established a design pipeline from computation to electrophysiology and biochemical characterization. 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 innovational computational design methodologies.

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Programme(s)

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Topic(s)

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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2023-STG

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Host institution

VIB VZW
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.

€ 1 499 250,00
Address
SUZANNE TASSIERSTRAAT 1
9052 ZWIJNAARDE - GENT
Belgium

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Region
Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent
Activity type
Research Organisations
Links
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 831 287,50

Beneficiaries (1)

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