Laboratory Head: Dr Daniela Stock
Group Leader: Dr Merridee Wouters
The Structural and Computational Biology Program seeks to understand the function of the heart in health and disease at the molecular level. While researchers in the Computational Biology Group analyse databases containing information about molecules involved in normal and abnormal physiological processes, X-ray crystallographers within the Structural Biology Laboratory visualise molecules of interest at near atomic resolution. Understanding the molecular mechanisms of proteins that are central to the development, maintenance and proper functioning of our hearts is crucial for diagnosis, drug design and treatment of disease.
Dr Daniela Stock's Laboratory
Daniela Stock's Laboratory uses X-ray crystallography to determine the three dimensional structures of proteins at high resolution. To achieve this the proteins of interest need to be isolated from their cellular environment, purified from contaminating proteins and crystallised. The crystals are then taken to synchrotrons, where X-ray diffraction data is collected. Processing of the data followed by Fourier transformation yields an electron density of the protein that allows interpretation of its structure at near-atomic resolution. Visualisation of proteins on computer screens, comparisons to other protein structures and to structures of mutated forms in genetic disorders provide a powerful tool to understand the molecular mechanisms of the protein both in health and in disease.
The laboratory is particularly interested in the structure of membrane proteins and macromolecular assemblies involved in biological energy conversion. Both represent challenges for structural investigations, as membrane proteins are intrinsically more difficult to crystallise than soluble proteins. The same holds for molecular motors as their dynamical nature prevents them from forming highly ordered crystals. In both cases additional tricks need to be applied to stabilise individual conformations or to create larger hydrophilic surfaces that will help to form crystal contacts.
Dr Merridee Wouters' Group
While medical research has seen outstanding progress in recent years with the development of drugs to combat disease, we still understand less than 1 percent of our own biology. The complexity of the problem is beyond the understanding of a single researcher. For this reason, computers are becoming increasingly important in medical research. Data gained from patients and laboratories around the world, which is traditionally shared through the scientific literature, is now additionally pooled into huge databases such as the Human Genome Database.
The Computational Biology and Bioinformatics Group "mines" databases which contain information about molecules involved in normal physiological processes as well as pathological disease processes. Computer visualisation of molecules enables us to understand them in a more intuitive way. Access to computer databases allows us to immediately gather any previous results on analogous systems which may inform further experiments by laboratory researchers. Database searches allow us to gather and synthesise information to deduce general rules for systems.
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