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Towards tracing chromosomes at super-resolution


  Guy Nir [1]  ,  Son C. Nguyen [1]  ,  Alistair Boettiger [2]  ,  Bogdan Bintu [3,7]  ,  Brian Beliveau [4,8]  ,  Geoffrey Fudenberg [5]  ,  Ruth B. McCole [1]  ,  Jelena Erceg [1]  ,  Leonid Mirny [5]  ,  Peng Yin [4,8]  ,  Xiaowei Zhuang [3,6,7]  ,  C-ting Wu [1]  
 [1] Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
[2] Department of Developmental biology, Stanford University, CA 94305
[3] Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA
[4] Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA
[5] Massachusetts Institute of Technology, Cambridge, MA 02139
[6] Department of Physics, Harvard University, Cambridge, MA 02138, USA
[7] Howard Hughes Medical Institute, Cambridge, MA 02138, USA
[8] Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA

Questions concerning the impact of chromosome organization on inheritance and gene expression raise some of the greatest technical challenges known to geneticists as well as many soft matter biophysicists. Not only does chromosomal DNA embody the largest biomolecules in the cell, but each chromosome is comprised of countless segments that fold independently in ways that vary from cell to cell. Finally, excepting the X and Y, chromosomes of diploid organisms come in nearly identical pairs, the members of which, called homologs, defy distinction via imaging. Here, I will present how we are now set to hone a suite of new tools developed in our laboratory for imaging whole chromosomes at the single cell level in a sequence-, and homolog-specific fashion using super-resolution microscopy. In this talk, I will show how we are now imaging, and then, analyzing images of super-resolved sub-chromosomal structures, to then recapitulate biophysical characteristics of chromosome structure.