Tor 23 maj / År 42 / Nr 1 2024

Collaboration AstraZeneca´s Efficient Way to New Drugs

Discovery Sciences, a department at AstraZeneca´s research unit in Mölndal just south of Gothenburg, has grown in importance during recent years.
Its goal is to discover compounds for disease treatment that are based on new knowledge of the human genome, cell structures and human proteins. A research effort that is extremely complex and technically demanding. In this respect collaboration across functional and geographic boundaries is a key enabler. “Success will only come our way if we can combine internal collaboration across our research units with external partnerships at regional, national and global levels,” says Peter Nyström, Site Manager at AstraZeneca in Mölndal.

X-ray diffraction of membrane bound proteins. Sounds complicated? Well, that’s exactly what it is. The barely understandable words are never the less an important motivator to AstraZeneca’s focus on Discovery Sciences. It all boils down to identify and understand how different compounds bind to proteins present at the surface of cells in the human body to discover new cures to our diseases. The research represents the fundamental and most basic part of the emerging possibility to produce new medicines that can enhance the future for millions of patients.
AstraZeneca in Mölndal employs about 170 researchers at Discovery Sciences, many from Sweden but also a whole range of scientists from abroad covering a number of different nationalities. The researchers we meet are a typical example: Niek Dekker, the Netherlands, Stefan Geschwindner, Germany and Margareta Ek, Sweden. All three are aiming to find the molecules that can influence human cells and deliver better cure for severe pain, life threatening obesity and lung ailments such as COPD (Chronic Obstructive Pulmonary Disease).

A more open approach
“A lot has happened in recent years that’s dramatically has brought this kind of science forward. But at the same time tools and techniques have become so extremely complicated that we at AstraZeneca now has to work by open processes and collaborate, with other companies, and with the academic world,” says Stefan Geschwindner. A good example of this is in the research of proteins that bound to our cells protective outer
membrane. Cell surfaces are filled with a vast number of receptors at which substances coupled to proteins can be fed into the cell itself and affect the way it operates. Today this is an unbeatable way to introduce drugs that will work exactly where they should. But how will one find the right proteins that will administer the right drugs? “We obviously start from the problems that the patients in healthcare experience. The concrete ideas then stems from scientists, practicing doctors – and from large databases of potential medicinal substances that the company has sampled during many years,” says Margareta Ek.

Particle accelerators sometimes do the job
In short the scientists try to determine the exact structure of the proteins found. They crystallize the compound together with the target protein and then expose these crystals to high intensity X-ray diffraction to be able to solve the three dimensional structure. Knowing
how a compound binds to its target protein is an enormous help in the further optimization of such a compound to a novel candidate drug.
Although AstraZeneca in Mölndal do have advanced X-ray detectors, these do not always manage to produce the energy levels that fully enable them to “see” the details of the protein structures.
“If this problem occurs we collaborate with the ESRF in Grenoble, France, and apply their gigantic particle accelerator for the job,” says Niek Dekker.

The future spells collaboration
There are also plenty of partners closer to home than Grenoble and other parts of the world. The Gothenburg region provides many opportunities. For example; Chalmers University of Technology, Sahlgrenska University Hospital and the University of Gothenburg; all are close collaborators to AstraZeneca. Stefan Geschwindner tells us:
“In collaboration with Chalmers Innovation we are for example eveloping methods to achieve higher concentrations of cell binding proteins and, in principle, we will be able to identify only a single protein binding molecule at a time, giving us more exact measurements”.
Another example is the collaboration with the University of Gothenburg, together with ten other laboratories in Europe, where the aim is to develop new computerized analysis methods providing a better way to identify the cell membrane binding protein structures.

An additional objective for AstraZeneca in Mölndal is to open its corporate databases, containing research results of a vast number of substances, to researchers from many universities. “We are convinced that collaboration is the key promoter to achieve a successful delivery of new medicines in our increasingly complex world of research,” says Site Manager Peter Nyström.