Two new professors continue protein research

Knowledge of protein structures and properties at atomic level is becoming increasingly important as protein-based pharmaceuticals have proved to be more secure and effective than conventional pharmaceuticals. Several modern pharmaceuticals therefore contain proteins. Likewise, several industrial products such as food products, washing powder, and bio-ethanol are produced by means of proteins or with proteins as an active ingredient. And through close collaboration at DTU Chemistry Pernille and Günther have contributed with research results in this field for many years.

“Protein-based pharmaceuticals have the advantage that the proteins are biologically active, effective, and specific in their reactions. Therefore, they will often have fewer side effects than other medicines,” says Pernille Harris.

Pernille has been Associate Professor at DTU since 2002 and is pleased with her new title of Professor, because even though there are many advantages of using proteins in pharmaceuticals, it also still poses many challenges. And there is still a great need for protein chemistry research.

“One of the challenges of protein-based pharmaceuticals is to ensure the long-term stability and activeness of the proteins. If they’re stored incorrectly, either during production or in the finished medicine - at the wrong temperature, pH value etc. - they will often precipitate and become inactive, or even worse, cause unwanted side effects,” she explains.

"Each protein has its own special properties, and this makes great demands on production and formulation of pharmaceutical proteins,” says Pernille.

Research into excipients and stable proteins
Both Pernille and Günther are working on a major pan-European Horizon 2020 project named PIPPI. The aim of the project is to map the excipients which can make proteins stable. And they are continuing this work.

“Many different excipients are used in the finished medicine to ensure that the proteins remain stable. The excipients don’t have any medical effect, and their sole purpose is to make the medicine stable. And even though work has been conducted with formulation of proteins for many years, there’s still a need for in-depth knowledge at the molecular level. In the PIPPI project, we’re working to acquire this knowledge and to achieve a molecular understanding of how different types of excipients stabilize proteins, so that we can become better at choosing the best methods,” explains Pernille, who is manager of the project.

Towards an overall database
The PIPPI project has entered its final stage and will be concluded at the end of the year. The result will be a database containing raw data with information about the effects of the excipients and interactions with proteins. The database is the first of its kind, and it will hopefully be of great importance in the future, because researchers are constantly becoming better at utilizing and comparing large quantities of data.

In their day-to-day work, Pernille and Günther work closely together in an iterative process.

“Where Pernille studies proteins by means of X-ray scattering, light scattering, and other spectroscopic methods, I perform calculations and modelling on the computer. Using in silico methods, we can recreate the behaviour of proteins by changing physicochemical conditions and the addition of excipients. We test the proteins under many different conditions. In this way, Pernille and I work together in an iterative process, in which we both perform laboratory tests and create models on the computer,” says Günther.

He emphasizes that the synergies between experiments and modelling are fundamental in obtaining an understanding of the behaviour of proteins at molecular level.

Günther originally graduated in the United States, and he came to Denmark in 1992, where he has—among other positions—worked as a Postdoc in protein chemistry at the University of Copenhagen and in the Danish pharmaceutical industry. He consequently has good knowledge of the challenges involved in characterization of proteins in the industry, and he is confident that the new database will be helpful in this process.

Greater utilization of data on proteins
However, there are still many aspects of the interaction of proteins with excipients that need to be examined, and—like in many other areas—the volume of data just keeps growing. In fact, Günther and Pernille agree that there are great future possibilities in using Machine Learning to find patterns in all the data available on proteins and their interaction with excipients in different solutions. And as Günther has been appointed Professor with Special Assignments (MSO), he is now considering which assignments could be relevant for the Department’s future research.

“Machine Learning is an example of an obvious area in which I would like to collaborate with experts at the other departments here at DTU—but also externally—and it could give us even more analyses and results, while also being an exciting element for the students,” says Günther.

Günter and Pernille are both keen to attract students to conduct research into protein chemistry, because there is such a large need for greater in-depth understanding of the behaviour of proteins, and graduates with such expertise are in high demand in the biotechnology industry. DTU Chemistry has therefore created a study programme in protein chemistry, of which Günther is the Head of Studies.