Welcome to Section on Physical Biochemistry @ NICHD.NIH
Our mission is to develop methods for diagnostics, monitoring and treatment of diseases based on a better understanding of underlying molecular mechanisms. We conduct the following studies:
We investigate molecular mechanisms of collagen-related and proteoglycan-related diseases ranging from rare genetic disorders of bone and cartilage to common forms of fibrosis. Often, these studies begin with patients who have poorly understood or mismatching symptoms and mutations. We work with cells and tissue samples referred by clinicians as well as with mice engineered to mimic some of the patients' disorders. We develop and use physical and biochemical techniques to study molecules likely to be involved in the respective disease. Our progress in these clinically oriented projects would be impossible without in-depth, fundamental studies of collagen folding, stability and interactions with other molecules also conducted in our laboratory.
To obtain further insights into mechanisms of these diseases, we utilize our recent technological advances in infrared and Raman micro-spectroscopic imaging of collagen, proteoglycans and other crucial components in bone and cartilage. Building on these advances, we are developing high-definition, label-free hyperspectral imaging technology for real-time monitoring of homeostasis and biochemical reactions in solvated tissue sections and live cell cultures.
The studies of collagen interactions have led us to discover more general laws that govern electrostatic interactions between any rod-like macromolecules with helical structures. A rigorous physical theory relating interactions between biological helices to their structure has proved to be useful for understanding the forces involved in hydration of collagen fibers, condensation and polymorphism of DNA, and a number of other phenomena. In collaboration with colleagues at Imperial College in London, we continue developing related theoretical models, e.g., of DNA supercoiling and liquid crystalline phases.
One of the most interesting predictions of our theory is that DNA molecules may have an innate ability to recognize mutual sequence homology without the double helix disruption and formation of single-strands. Our recent in vitro observation of pairing between homologous double-stranded DNAs in a protein-free environment supports this idea, and we are continuing its further experimental testing. We are particularly interested in clarifying whether such sequence recognition is involved in homologous DNA pairing in cells, which is crucial for maintaining genetic diversity and repairing DNA damage. (To learn more about potential significance of these studies, see recent commentary by Prof. Falaschi).