Nancy Kleckner, Ph.D.
Department of Molecular and Cellular Biology, Harvard University
Chromosome Mechanics and Dynamics
We are interested in complex chromosomal behaviors that lack satisfactory explanations. We emphasize new approaches, quantitative analysis and hypotheses that are orthogonal to general dogma. Current work combines 4D (3D-plus-time) imaging of single cells at high spatio-temporal resolution with genetic, molecular and in vitro approaches. Undergraduates, graduate rotation students and post-doctoral fellows are welcome, particularly those who wish to study chromosome dynamics using analytical methods from physics and engineering (in combination with genetics).
Subjects of interest include:
•3D super-resolution time-lapse microscopy - a new imaging approach for point source and whole object imaging in low signal-to-noise regimes.
•Global chromosome expansion/compaction stress cycles - a new universal principle from bacteria to mammalian cells.
•Mammalian chromosome morphogenesis, replication and 4D dynamics.
•Lessons from bacteria for higher organisms: how does E.coli segregate its sisters without a spindle and coordinate its chromosomal and cell division cycles without a cell cycle engine?
•Homologous chromosome pairing of whole chromosomes in yeast and mammalian cells and pairing for silencing of repeats in Neurospora.
•Spatial patterning of meiotic crossovers (crossover interference): in real time and space in C.elegans and roles for female aneuploidy in human meiosis.
Kleckner, N., Zickler, D., Jones, G.H., Henle, J., Dekker, J. and Hutchinson, J. 2004. A mechanical basis for chromosome function. Proc. Natl. Acad. Sci. USA, 101, 12592-12597.
Fisher, J.K., Bourniquel, A., Witz, G., Weiner, B., Prentiss, M. and Kleckner, N. 2013. Four-dimensional imaging of E. coli organization and dynamics in living cells. Cell 153, 882-895. PMCID: PMC3670778
Liang, Z., Zickler, D., Prentiss, M., Chang, F.S., Witz, G., Maeshima, K. and Kleckner, N. 2015. Chromosomes progress to metaphase in multiple discrete steps via global compaction/expansion cycles. Cell 161: 1124-1137. doi10.1016/j.cell.2015.04.030. PMCID: PMC4353236
Grinthal, A., Adamovic, I., Weiner, B., Karplus, M. and Kleckner, N. 2010. PR65, the HEAT-repeat scaffold of phosphatase PP2A, is an elastic connector that links force and catalysis. Proc. Natl. Acad. Sci., USA, 107, 2467-2472. PMCID: PMC2823866
Fisher, J.K. and Kleckner, N. 2014. Magnetic Force Micropiston: an integrated force microfluidic device for the application of compressive forces in a confined environment. Rev. Sci. Instrum. 85 023704 (2014); http://dx.doi.org/10.1063/1.4864085, (issue date Feb. 14, 2014). PMCID: PMC3970836.
Burgess, S.M., Kleckner, N. and Weiner, B.M. 1999. Somatic pairing of homologs in budding yeast: existence and modulation. Genes Dev. 13, 1627-1641.
Zhang, L., Wang, S., Yin, S., Hong, S. Kim, K.P. and Kleckner, N. 2014. Topoisomerase II mediates meiotic crossover interference. Nature 511: 551-556. PMCID: PMC4128387.
Gladyshev E. and Kleckner, N. 2014. Direct recognition of homology between double helices of DNA in Neurospora crassa. Nat. Commun. 5: 3509 doi: 10.1038/ncomms4509. PMCID: PMC4000310
52 Oxford Street
Cambridge, MA 02138