ESF Eurocores SONS Project NanoSMAP

The ASMENA Project: An Introduction

The ASMENA project aims to create new platforms for drug screening and analytical profiling based on in vitro direct measurements of membrane protein and conformational changes. Such tools will allow standard profiling and screening also against membrane protein targets, shorten time and cost in drug lead development by increased predictability as well as contribute to fundamental understanding of structure-function relationship of membrane proteins.

Motivation

Current drug screening assays targeting membrane proteins rely to a large extent on flourescent recording. Labels are an unnatural attachment/component to the molecule to be investigated and may affect its biochemical behaviour. In the worst case this leads to false readouts. Thus, there is a strong desire to transfer fluorescence recording into label-free formats.

The ASMENA project aims to develop methods to self-assemble membrane protein-containing lipid bilayers onto nanoporous substrates designed for both electrochemical recording of function and label-free nanoplasmonics compatible with an array format for membrane protein drug screening assays. The objective is to develop a versatile platform that can easily be scaled up for analytical profiling to functional screening of drug interaction with membranes and several classes of membrane protein which are potential drug targets.

Cell surface receptors comprise a vast number of structurally diverse integral membrane proteins. Understanding cellular signalling mediated by cell surface receptors is in the focus of present biological research and central for drug development. The need for downscaling assay formats is of utmost importance for accelerating functional screening, reducing costs by earlier detection of potential drug hits or toxicity effects, reduced reagent consumption, and open novel possibilities which cannot be reached by traditional techniques.

The main objectives can be summarized as a generating the scientific and technological know-how to achieve:

1. an electrochemical sensor platform for ion channel/transporter drug screening/analytical profiling

2. a local surface plasmon resonance sensor platform for aquaporin drug screening/analytical profiling

3. a membrane protein functionalized waveguide sensor platform for drug screening/analytical profiling based on self-assembled proteolipid membranes and label-free sensing.

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