New CD Laboratory: Folding Proteins Correctly

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Oliver Spadiut in the lab
Oliver Spadiut in the lab
When proteins are produced in the pharmaceutical industry, they are often initially misfolded and have to be rearranged. At TU Wien, this is being studied in detail in a new CD laboratory.

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. However, when such proteins are produced artificially, there is always a problem: they are initially folded incorrectly. Instead of a functional protein, you get what is known as an inclusion body, which first has to be brought into the correct shape in laborious and expensive steps.

A new Christian Doppler Laboratory has now been opened at TU Wien - with the support of corporate partner Boehringer Ingelheim RCV and the Federal Ministry of Labor and Economics. Research is now being carried out there into how the inclusion bodies can be brought into the right shape most efficiently. The goal is to understand the process precisely at the fundamental level and to reproduce it as a computer model. This should make the production of these proteins faster, more environmentally friendly and more cost-effective.

-This CD Laboratory aims to make the production of certain biopharmaceuticals more targeted, more efficient and more sustainable, thus enabling shorter development times, more environmentally friendly processes and cheaper drugs - a great advantage for patients and also for Austria as a life science location as a whole," says Minister of Labor and Economic Affairs 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 customized protein has now 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 obtained: -It depends on the complexity and three-dimensional structure of the protein,- explains Oliver Spadiut from the Institute of Process Engineering, Environmental Engineering and Technical Biosciences at TU Wien, the head of the new CD lab. -If the protein folds incorrectly, the result is an inclusion body, a more or less non-functional ball of amino acids that cannot be used.-.

The amino acid chains trapped in these inclusion bodies must first be converted. To do this, it is first unraveled 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 assume 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 you often have to rely on trial and error here. People know from experience how to control the process 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 thanks to the new CD lab: Oliver Spadiut and his team want to precisely analyze 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 be more resource-efficient in general. It’s good for industry - new processes can then be developed more quickly and reliably because the optimum strategy can be determined on the computer without having to spend a lot of time trying things out. And it’s also good for the healthcare system - the resulting pharmaceutical products should become much more cost-effective and reach the market more quickly.

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 funded by the public sector and the participating companies. The most important public funding body is the Federal Ministry of Labor and Economic Affairs (BMAW).