Major research project may lead to better drugs to treat chronic pain

Birkbeck wins prestigious £532,416 grant to continue groundbreaking scientific study

A four-year study worth £532,416 could lead to the design of better drugs for treating chronic pain and neurological diseases such as epilepsy, and heart disease. Professor Bonnie Wallace, Professor of Molecular Biophysics in Birkbeck’s Department of Biological Sciences and joint Birkbeck/UCL Institute of Structural and Molecular Biology, has been awarded the research grant by the Biotechnology and Biological Science Research Council (BBSRC).

The grant will enable Professor Wallace’s research team to continue their study of the structure and function of sodium channels – pores in the membranes of excitable cells, such as brain or heart cells, which open and close selectively to allow the passage of millions of charged particles, or ions, across the cell membrane.   This movement generates electrical signals which encode and process information in the brain and nervous system, making heart muscles contract or nerve cells to signal pain. Sodium channels in particular are important molecules because they regulate a wide range of physiological activities.

Professor Wallace (pictured far right) explained:  “If something goes wrong with these channels, a range of different diseases can occur depending on which channels are affected – you can get chronic pain (estimated to affect more than 30% of the adult population) if it is in peripheral nerves, or if it’s the channels in the brain that go wrong you can get epilepsy, or if in your heart, cardiac arrhythmia.

Crystal structures

“This grant is to help us understand how the sodium channel works and to look at the difference between sodium, potassium and calcium channels, which do similar, but, importantly, different jobs. In cells an exquisite choreography of the timings of opening and closing of the different channels is essential for their proper functioning. This grant will enable us to determine the crystal structures of a number of naturally-occurring and mutant sodium channels and other related ion channels, and compare their structures with functional studies to better understand the means by which the channels open and close.

“Understanding this will ultimately enable us to think about the impact on diseases, as many pharmaceutical drugs for treating pain, epilepsy and cardiac diseases act on sodium channels.  In addition, in insects, these channels are the target sites of many insecticides, which, critically, bind to insect sodium channels, but not human channels. Many eventually develop resistance to insecticides and so new ones need to be developed.

“By examining these channels we should be able to enhance the development of new and highly specific insecticides and pharmaceutical drugs.”

The BBSRC grant will support the work of two post docs, Dr Claire Bagnéris (pictured centre) and Dr Claire Naylor (pictured left), whose research with Professor Wallace previously led to breakthrough publications in this area.

The ability to visualise the structural details of the sodium channel was made possible using advanced methods of X-ray crystallography, spectroscopy, and computational analysis in the laboratory at the ISMB.

Impact on health

Professor Wallace added:  “We’re delighted to have this grant in 2014, the International Year of Crystallography, as Birkbeck’s department has a long and important history as leaders in the establishment of crystallography.

“We are carrying on that tradition, and the Institute of Structural and Molecular Biology has a large part to play in this - it has the facilities, the expertise and the environment necessary to be able to do such complicated work.

“We expect to produce results within four years, but there is a long timeframe between basic science results and seeing any impact on human health – at least a decade from now. However, it is important that this grant supports really blue skies research, because without it there would be no applications that will eventually have impact on our daily lives.”