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Research Homepage of Nick Kinney

Dr KinneyThe overall goal of my ongoing research is to develop a better understanding of 3D genome organization through polymer modeling, simulation, and experiment. This research builds on fundemental scientific concepts. Even high school students learn that the nucleus is a hallmark of all eukaryotes; however, little is known about how chromosomes fold within its boundaries. This is important because experiments suggest that chromosome folding affects gene expression. Thus, genome sequences must be understood in the context of their 3D organization which critically influences the flow of information. The effort to understand this added complexity now encompasses an entire field of chromosome biology and is reshaping the traditional concept of the central dogma.

My interdisciplinary background has allowed me to study 3D genome organization using a combination of computational polymer modeling and experiment. Unlike most proteins that adopt the same 3D shapes in all cells, the conformations of the chromatin fiber are stochastic to some degree. Despite this added complexity, many computational models of genome organization start from a simple random walk. A random walk in 3D can be conceptualized as a series of steps beginning at the origin and randomly moving in units along each coordinate axis. Remarkably, ensembles of these simple walks can explain some aspects of 3D genome organization. The dynamics of a random walk model can then be simulated with the Langevin equation of motion.

My experimental approach to studying 3D genome organization takes advantage of polytene chromosomes in fruit flies. Each polytene chromosomes replicates without cell division and forms a bundled fiber of approximately 1024 individual strands aligned in parallel; consequently, the chromosomes in the nucleus become visible with a light microscope. This is a critical advantage over regular interphase chromosomes because it's possible to obtain spatial information about the position of each chromosome in 3D using relatively simple techniques. So far this research has resulted in several published manuscripts; upcoming publications incorporate experiments that use confocal microscopy and florescent labeling.