How to prevent degeneration of protein structure?
New molecular knowledge can give hope for patients with Føllings disease.
Professor Aurora Martinez and her research group at the Department of Biomedicine has carried out research that is important for our understanding of the molecular mechanisms underlying inherited disease, and hopefully will provide future possibilities for cure.
Professor Martinez and her research group was in 2009 awarded the prize for the ”Best basic research publication in 2008” at the Faculty of Medicine and Dentistry, University of Bergen. The prize was for an important paper regarding our understanding of the underlying mechanisms behind inherited disease, and future possibilities for developing a cure. In this case, Føllings disease: phenylketonuria (PKU), which is a result of a defect causing degeneration of protein structure (”misfolding”) and hence its function. The disease was discovered by the Norwegian physician, Asbjørn Følling, in 1934. This finding led to the establishment of a blood test that is taken six days after birth in order to screen for the disease. If undiscovered the disease can lead to brain damage. Those afflicted with the disease must keep to a controlled phenylalanine-free diet. At present the disease cannot be cured.
The research performed by Martinez and her colleagues related to Føllings disease is focussed both on causal factors at a molecular level, and the possibility of correcting misfolding. Both the methodology and the results can be therefore applied to many inherited diseases. This is because many diseases of this type often have a similar molecular genetic basis. In such cases there is an error in the structure and therefore function of the affected proteins in the body. The result being many serious and damaging side-effects for those suffering from these types of disease. The approach of Professor Martinez, and the results achieved so far, have generated new knowledge and can open up new avenues for ultimately providing solutions to these problems. In international research in this area there exist two main approaches with regards to curing these diseases: firstly, to produce new authentic proteins by gene- or protein-replacement therapy, and secondly to repair the affected protein, such that it functions normally in the body. The research performed by Professor Martinez belongs to the latter category of research.
The goal of her research group is to identify a component that will help the protein to regain its original structure, and thereby prevent if from being destroyed, and thus from disappearing. It is envisioned that in the future this will not only give hope to patients suffering from Føllings disease, but in addition also to those with different forms of inherited disease.
In the attached article Professor Martinez gives a detailed account of methods, results and implications of this area of her research.
See also the paper that received the award