In-depth knowledge of body’s signalling system may lead to greater drug efficacy
Researchers are investigating, at molecular level, how the human body has evolved to recognise various signalling substances. Their hope is to be able to contribute to the drugs of the future, with better therapeutic results and fewer side effects. Jens Carlsson of Uppsala University’s Department of Cell and Molecular Biology was recently awarded a project grant of SEK 28 million from the Knut and Alice Wallenberg Foundation (KAW).
The body’s cells communicate with one another by means of hormones and signalling substances. On the cell surface, there are signal receptors that convey the information to the cell interior. In this way, the whole organism’s activities, such as movement or metabolism, can be coordinated.
Since many important drugs act via receptors, it is important to understand in depth how a receptor recognises a substance, and also how this signalling system originated and has changed in the course of evolution. The new research project will focus on how the body’s receptors can distinguish between adrenaline, dopamine and other signalling substances. To find this out, there will be evolutionary comparisons of the amino-acid sequences and three-dimensional structures of the receptors.
Multiskilled team
The researchers running the project will make molecular models of receptors to identify their similarities and differences. These computer models will then be evaluated in new experiments.
“We’re a team with many different skills. We’re all working on the same family of receptors, but look at them from different angles,” explains project head Jens Carlsson, Senior Lecturer at the Department of Cell and Molecular Biology.
The new knowledge that the researchers hope to obtain in the project can, in the next stage, be used to develop drugs that are more targeted and have less severe side effects.
“If we understand these receptors in depth, we can create an entirely new receptor that recognises another molecule. That would be confirmation that we really understand how it works. And in the future, receptors like that could be used in gene therapy,” Carlsson says.
Linda Koffmar