I am a postdoc in Xiaowei Zhuang’s group at Harvard studying gene regulation in animal development through super-resolution microscopy approaches.
My research aims to improve our understanding of how cells with the same genome can develop dramatically different behaviors. For example, consider the mechanical abilities of a muscle cell compared to the electrical excitability of a neuron, or the industrious activity of bone building cells in a youthful person compared to an elderly one. Each of these cells, (if taken from the same individual) has an identical genome — and yet each is “reading” a very distinct subset of that genome and consequently carrying out very different behaviors. The choice of what to read and what to hide away is made during development. An increasing body of data suggests this is accomplished by modifying the genome both in the nature of the proteins bound to different sequences and in the topological organization of those sequences. Topology is particularly important, as many of the directions which tell a cell which genes to express at what time and what levels are encoded in DNA sequences that distant in sequence space from the genes they regulate. By folding these bits of DNA in different ways, a cell can change which regulatory sequences have access to which genes, and achieve different behavioral states.
So far these structures have eluded a direct study for want of methods that can visualize them. Conventional fluorescent microscopy has developed excellent tools for coloring specific regions of DNA and particular DNA-associated proteins with uniquely colored dyes — but lacks the resolution to turn these colored blurs into structures. Electron-microscopy has substantially greater resolution but lacks compatibility with specific labeling techniques to tell what’s what. ”Super-resolution” imaging approaches promise to address this balance by allowing the use of fluorescent labels while simultaneously resolving structures on the nanoscale.
For a more detailed introduction into current thought on genome architecture, epigenetic structure, and the implications of it all for gene expression, I recommend recent reviews by Dekker, Dubuole, Bickmore, van Steensel, Cavalli, and other pioneers of this field.
