Certain proteins are among the most important products of the pharmaceutical industry - such as insulin or interferons, which are used to treat diabetes, cancer or viral diseases. When such proteins are artificially produced, however, there is often a problem: they are initially folded incorrectly. Instead of a functional protein, a so-called "inclusion body" is formed that has to be brought into the correct shape in complicated and expensive steps.
A new Christian Doppler Laboratory has now been opened at TU Wien – with the support of the company partner Boehringer Ingelheim RCV and the Federal Ministry of Labour and Economy. Research is now being carried out there on how the inclusion bodies can be brought into the right shape most efficiently. The goal is to understand the process precisely at a fundamental level and to reproduce the process in a computer model. This should make the production of these proteins faster, more environmentally friendly and cheaper.
"This CD Laboratory aims to make the production of certain biopharmaceuticals more targeted, more efficient as well as more sustainable, thus enabling shorter development times, more environmentally friendly processes and cheaper medicines - a great advantage for patients and, moreover, for Austria as a life science location as a whole," says Minister of Labour and Economy Martin Kocher.
Right code, wrong shape
Proteins are always made up of the same building blocks - amino acids, the sequence of which is determined by the DNA code. Producing a tailor-made protein has become a relatively simple technical task: Take a microorganism, such as the bacterium E. coli, and alter its DNA so that it produces the desired protein. The bacterium can then produce the amino acid sequence that makes up human insulin, for example.
However, this does not mean that the desired product will be produced: "It depends on the complexity and three-dimensional structure of the protein," explains Prof. Oliver Spadiut from the Institute of Process Engineering, Environmental Engineering and Technical Biosciences at TU Wien, the head of the new CD laboratory. "If the protein folds incorrectly, the result is an inclusion body, a more or less non-functional ball of amino acids that you can't use."
First, the amino acid chains trapped in these inclusion bodies, have to be rearranged. To do this, the inclusion body is untangled with chemicals - much like unwinding a ball of wool into a straight thread. In the next process step, the protein folds up again and can take on its final, correct, medically desired shape.
Optimal planning instead of trial and error
"This technique plays an important role in the pharmaceutical industry," says Oliver Spadiut. "But often here you have to rely on trial and error. People know from experience how to control the process in order to achieve reasonably good results - but a comprehensive, fundamental understanding is still lacking. This circumstance makes it very difficult to further improve the process."
This is now set to change with the new CD laboratory: Oliver Spadiut and his team want to precisely analyse the path from the inclusion body to the functional protein, create a so-called "digital twin" of this process on the computer and thereby find out how to optimally control the process.
This is good for the environment - the process should use fewer chemicals and should be more resource-efficient in general. It is good for industry – it becomes possible to develop new processes faster and more reliably because you can determine the optimal strategy on the computer without having to spend a lot of time trying things out. And it is also good for the health system - the resulting pharmaceutical products should become significantly cheaper and reach the market faster.
About Christian Doppler Laboratories
In Christian Doppler Laboratories, application-oriented basic research is carried out at a high level. Outstanding scientists cooperate with innovative companies. The Christian Doppler Research Association is internationally regarded as a best-practice example for the promotion of this cooperation.
Christian Doppler Laboratories are jointly financed by the public sector and the participating companies. The most important public funding body is the Federal Ministry of Labour and Economic Affairs (BMAW).
Prof. Oliver Spadiut
Institute of Chemical, Environmental and Bioscience Engineering
+43 1 58801 166420