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Farfield lights up membrane protein analysis

By Dr Matt Wilkinson, 20-Jun-2007

Related topics: Products, Reagents (protein, genomic, PCR, cell-culture)

Farfield Scientific has teamed up with Monash University, Australia to create biosensor chips that will enable researchers to unravel how membrane proteins function and interact with drug molecules.

The collaboration will utilise Monash University's patented membrane protein technology to create a new range of disposable protein sensor chips to provide a way of measuring the how external forces, such as temperature, pH or the presence of drug molecules effects membrane protein structure.

"This collaboration will deliver a bioanalytical toolkit which will transform the life scientist's ability to unravel the mechanisms by which these proteins function and will ultimately lead to an entirely new approach to structurally informed drug discovery," said Dr Gerry Ronan, CEO of Farfield Scientific.

UK-based Farfield will develop the surfaces for use in its AnaLight dual polarisation interferometry (DPI) instrument that can resolve protein structure to below 0.01nm.

This enables researchers to characterise proteins without the need for laborious protein crystallisation and crystallography experiments.

The quantitative structural data generated on an AnaLight instrument can be compared directly with many complimentary techniques such as x-ray crystallography, NMR and neutron reflection allowing a wide variety of data to be collated and used together to answer difficult questions about protein structure and function.

"We've done a lot of work looking at Alzheimer's disease where the protein misfolding and aggregation causes the neurodegeneration," said Dr Ronan.

According to Dr Ronan, the technique is similar to Surface Plasmon Resonance (SPR) techniques, but instead of using a gold surface DPI uses a glass surface allowing the instrument to make two measurements at orthogonal polarisations at once.

By looking along the slide, rather than down onto the slide like you would with a microscope, the instrument can observe billions of molecules at once and by measuring the exponential decay of the two polarisations the refractive index can be calculated.

This can then be related to the size and mass of the objects on the slide giving researchers a unique real-time insight into protein size and structure and how those parameters are affected by drug candidate molecules.

"All neurotoxicity is associated with something attacking the neuronal cell wall - and to study the effects that potential drugs may have on this you have to have an environment where you can see if you are inhibiting that attack," said Dr Ronan.

Farfield currently supplies a range of 'AnaLight' sensor chips with a variety of surfaces that allow researchers to immobilise biomolecules on the prepared surface before reaction.

However, while this is suitable for many applications, immobilising cell membrane proteins in their native environment is more taxing and this is where the new chips will come into play, allowing researchers to order a chip onto which specific cell membrane proteins have been attached rather than having to make the chips themselves.

"This technology may lead to the identification of new proteins and drug targets for therapeutic development," said Associate Professor Marie-Isabel Aguilar, project leader at Monash university.

Recent work by researchers from Gifu University, Japan, used amine functionalised 'AnaChips' to immobilise and then study the Prion proteins (PrP) that are responsible for causing CJD (Creutzfeldt-Jakob disease) in humans and BSE (Bovine spongiform encephalopathy) in cows.

The results from the AnaLight instrument showed that as the PrPs are exposed to increasing concentrations of Cu2+ the dimensions of the protein decreased whilst the fold density increased. The Cu2+ formed a strong association with the PrP and was not released even after 180 seconds.

This implicates that the neurodegenerative symptoms observed in prion disease sufferers could be caused by a reduced availability of Cu2+ at synapses.

Farfield recently launched the Solaris photon injection system that allows structural dynamics studies of photo-responsive polymers and proteins in the AnaLight instrument.

This accessory was developed in collaboration with Professor Laszlo Kalman of Concordia University, Canada who is using it to study the primary processes of photosynthesis.

According to Dr Ronan, the company has doubled in size every year since they went commercial three years ago and now have about 70 instruments in use around the world.

"It's an exciting technology that is at the beginning of its journey and there are many more structural environments and applications that we want to explore," said Dr Ronan.