Prof Bert Klumperman from Stellenbosch University's Department of Chemistry and Polymer Science has been awarded a grant of R18 million by the Wellcome Trust to develop next-generation polymers for the successful isolation of membrane proteins.

Currently membrane proteins form about 70% of all drug targets in the field of nanomedicine, but progress is hampered because they are very difficult to isolate in their intact, stable and fully functional form.

The Wellcome Trust is a global charitable foundation that aims to address the world's most urgent health challenges by means of grant funding, campaigns and partnerships. The foundation is well known for pioneering new approaches to drug design, such as the antiviral AZT, the first drug approved to treat HIV.

Prof Klumperman has a long and established history in the research of an amphiphilic polymer, poly(styrene-co-maleic acid) or SMA. An amphiphilic polymer is a macromolecule that has both hydrophobic (water-repellent) and hydrophilic (water-loving) components. According to Prof Klumperman, in recent times SMA has gained significant traction as an effective agent for extracting and stabilising membrane proteins in phospholipid nanodiscs.

He explains: “Membrane proteins provide a multitude of functions essential to the life of the cell, and for that reason they can be extremely successful in the field of nanomedicine where we work with targeted drug delivery. Yet extracting these proteins in an intact, stable and fully functional form remains exceptionally challenging."

Since about a decade ago three commercially available polymers have offered interesting possibilities for the successful isolation of membrane proteins. But, explains Prof Klumperman, these commercially available polymers were never specifically developed for this type of application in the first place.

“In this project, we aim to develop the next generation of amphiphilic copolymers, dedicated for the isolation of membrane proteins. In collaboration with several specialists in this field, we want to enhance the efficiency of the amphiphilic copolymers and also introduce additional functionality that is needed to expand the utilisation of the isolated membrane proteins in the field of drug discovery and beyond."

The research project, titled “Unshackling Membrane Protein Research: New Amphiphilic Copolymers for Extraction of Stable, Active Membrane Proteins", will run over five years and involve at least six postgraduate students. The project will be carried out in close collaboration with Prof Tim Dafforn, an expert in biophysical spectroscopy in the School of Biosciences at the University of Birmingham in the United Kingdom. As co-principal investigator on the grant, the polymers developed in Stellenbosch will undergo general testing in Prof Dafforn's group. For specific applications there are bilateral sub-projects that involve membrane protein researchers from the UK, Denmark, the Netherlands, South Africa and Canada.

On the photo, from left to right: Prof Bert Klumperman and his team of postgraduate students, including one postdoctoral fellow: Lauren Ball (PhD-student), Sinothando Sibariboyi (PhD-student), Ruvimbo Chagwedera (PhD-student), Michael-Phillip Smith (MSc-student), dr Chandré Smit (post-doc) and Gestél Kuyler (PhD-student). Photo: Stefan Els