The perfect cell-free expression system for your membrane proteins

At InSingulo, we pride ourselves on enabling you to discover drugs for your most challenging targets. For many, that means membrane proteins. Most of the attempts to study membrane proteins have involved processing them to a very high degree, cutting them, removing them from the membranes and modifying them so that these challenging proteins can forced into our existing drug discovery workflows.

There’s an obvious problem to that. Membrane proteins that are processed to a high degree bare no resemblance to the targets in their natural state. Of course, we’ve been aware of this for a long time but the alternative was to not study membrane proteins at all which was clearly not an option.

But today there is an alternative. At InSingulo we take membrane proteins as they are and allow you test compound libraries against targets in their native conformation, embedded in the lipid bilayer.

Our hope is to forever change how drug discovery on membrane proteins is done which is why we are so happy to have a partnership with Synthelis, who are also committed to improving the way we do drug discovery on membrane proteins.

Synthelis realised that there are problems with the way that we produce proteins for drug discovery. Today we require larger fermenters and to over-express our target proteins in bacteria. This has a number of disadvantages, for example, at high concentrations many proteins become toxic to the cells producing them.

The team behind Synthelis thought that we could use the complex cellular machinery and use it to manufacture proteins in cell-free environment. If you have all the enzymes and components to produce proteins, why do you need the cell?

It turns out that you don’t need the cell to produce proteins and so, Synthelis was born to commercialise this important new technology. They discovered a number of additional benefits to producing proteins using their cell-free method:

·        It’s much faster – you can produce your proteins in 1 day

·        You get high production and folding efficiency because it’s easy to modify the expression conditions in a cell-free system

·        The protein production machinery is 100% devoted to your protein of interest in a cell-free system as there is no need to produce additional host proteins. This significantly increases yield

But what does this have to do with membrane proteins? Well, Synthelis can produce cell-free proteins inside synthetic liposomes as well. By enzymatically synthesising proteins in close proximity to the liposomes, it is possible to efficiently and correctly incorporate proteins into the membrane.

At InSingulo, we performed a proof-of-concept study with a membrane protein producing by Synthelis and got some really nice data. We believe that this will for the basis of a strong collaboration for further characterisation of membrane proteins in the future using two powerful tools, the production capacity of Synthelis and the detection capability of InSingulo.

If you’re interested in membrane proteins and this new excites you then please get in touch, we’d love to collaborate on more projects. However, the truth is that between Synthelis and InSingulo, we now have the foundation to perform our own drug screens on challenging transmembrane targets which is exactly what we hope to do.

Synthelis CEO, Bruno Tillier said, ”It’s great to see what two early stage companies can do when we come together. We have both worked hard to build talented teams and develop new technologies to change the way we look for drug candidates for challenging targets. Our technologies are so complementary that by working together we’re tapping into a whole world of potential that has previously not been available for membrane proteins.”

If you’d like to know more about our platforms for studying challenging targets. Please get in touch via the contact us page.