New approaches to high throughput protein isolation purification and concentration

There is a new generation of medicines under development that are based on natural molecules such as proteins or DNA. These will potentially be safer and more effective than current medicines but they are much more difficult to manufacture. Generally proteins are made in cells by biotechnology methods that are similar to those used in the fermentation of beer and wine. However, separation of the pure protein from the rest of the cell is much more challenging than the harvesting of ethanol. In this project we will investigate a new separation process based on coating proteins on the surface of crystals. This technique is known to work well with pure proteins but here we will investigate if it can be applied to the complex mixtures produced when processing cells. The aim will be to find specific conditions where the target protein can be purified from the other proteins and other cell components. If successful the reseach could potentially help speed up the development and reduce the cost of protein based medicines.

This project will investigate non-chromatographic methods for purifying proteins based on selective coprecipitation of the target in the form of protein coated microcrystals (PCMC). The resultant precipitated PCMC particles consist of protein immobilised on the surface of a crystalline excipient carrier and are stable for long-term storage. The techniqe is expected to be particularly useful for isolaton of complex protein assemblies not well suited to chromotography. We will investigate how coprecipitation compositions can be tuned to maximise selectivity and stability via changes to parameters such as excipient, solvent, pH and ionic strength. The scale-up potential of the process will be evaluated.