Work packages

The tasks to be accomplished within the ASMENA Projectis divided into 7 work packages.

Work Package 1: Fabrication of nanostructured supports

In WP1 we develop the necessary processes and platforms for the various nanopore sensor setups that will be employed throughout the project. In three separate but intertwined sub-projects we will develop platforms for nanopore electrochemical (EC) sensing, local surface plasmon resonance (LSPR) sensing, a combined EC and LSPR sensor platform and integrated microfluidics for advanced sample handling.

Work Package 2: Chemical surface functionalisation of nanoscale features for guiding assembly and sensor integration of (proteo)lipid membranes by function

In order to ensure that lipid membranes incorporating different membrane protein function can be assembled on selected spots on a sensor array, strategies for guided and triggered self-assembly on the nanostructures will be developed. Chemical functionalisation of the surface will be used also to ensure correct membrane protein orientation and position in the evanescent field, as well as no diffusion outside the sensing spot and high electrical resistance seal, for which new polymeric tethering strategies have to be developed.

In WP 2 a combination of tried approaches to surface functionalisation with development of new polymer coatings will be explored in order to achieve the overall objectives of: site-selective fusion of proteolipid membranes with high electrochemical seal resistance onto array spots with no inter-diffusion and high retained membrane protein functionality. Additional properties of the surface coatings will be no non-specific proteoliposome adsorption and functional groups allowing specific binding of DNA and proteins as well as switchable properties for controlled biomolecular interaction.

Work Package 3: Formation of planar lipid bilayers on nanostructured surfaces

WP3 focuses on bringing together the technology platforms developed in WP1 and WP2 in order to achieve spontaneous formation of nanopore-spanning lipid bilayers (npsLBs) through induced fusion of vesicles, which will be instrumental to investigations in WP5 and WP6. In addition, a combined experimental and theoretical approach will be used to explore the parameters that determine the long-term stability and electrochemical seal of proteolipid membranes which are critical limiting factors for the industrial applications.

Work Package 4: Integration of transmembrane protein assays with waveguide biosensors

In this work package we focus on adapting protocols developed in earlier WPs to functionalise waveguide sensor systems by industrial partners #11 and #12 for various screening assays. WP4 also has a high content of theoretical analysis and simulation to understand and develop new sensitive assays for deducing changes in membrane and membrane protein conformation in addition to pure affinity assays.

Work Package 5: Functional assays of membrane proteins

WP5 explores the npsLB platform for activity measurements on several different model systems.

Work Package 6: Application for drug screening

We will make use of the materials and methods acquired in previous WPs to develop a prototype system for a functional assay for drug screening against membrane protein targets. In a first phase emphasis will be put on quantitative measurements of membrane protein, allowing automated control of electrochemical and optical detection of effector compound binding and its effect on drug target activity. In the next phase integrated microfluidics developed in WP1 will be used to establish a prototype system to monitor membrane protein activity under screening of libraries of effector compounds. Additionally, the same setup will be explored as platform for investigating drug lead-membrane interaction and permeation.

Work Package 7: Management Activities

ASMENA is coordinated by Marcus Textor (PC), Professor at the Department of Materials, ETH Zurich. The overall management responsibility lies with the PC. He is supported by an ETH-based organising committee consisting of the PC, Prof. Janos Vörös, Head of the Laboratory for Biosensors and Bioelectronics, Dr. Erik Reimhult, a senior researcher with an excellent background in the field of membranes and biosensing and experience in project coordination, an administrative staff member of the Department of Materials and an additional staff member from the ETH EU research coordination office (EUresearch). The members of this committee take care of the daily organisational tasks and guarantee appropriate communication between all partners and with the Industrial Advisory Board (IAB, see below).

The General Assembly (GA), led by the PC and consisting of one representative of each consortium partner will meet at least once per year. Additionally, one meeting with all or most partners is expected to be organised each year. The GA will comprise one senior representative from each partner and have additional participation of (but no voting rights for) personnel working within ASMENA from all partners

All partners have agreed on establishing an Industrial Advisory Board (IAB), to meet once a year, with executive-level reporting every 6 months. The IAB will evaluate and advice on overall strategy, good governance and longer term planning. In particular, proposing strategies regarding implementation of technology on an industrial level, coordination of interests and activities among the industrial partners regarding prototyping and future commercial exploitation, patent and licensing strategies. Within ASMENA the IAB has an advisory role and reports its evaluations and findings to the PC and the GA.

The Work package Leaders (WPL) will

- manage the scientific and technical aspects of the work package;

- organize work package meetings to discuss progress, problems and newly emerging ideas;

- maintain close contact with all work package participants;

- report to the PC on progress, problems as well as on the milestones, deliverables and financial aspects of the work package.

The members of each work package will provide progress reports and updates on the work plan to the WPL.