Since
their discovery almost 150 years ago, chromosomes have been shown to
represent a fundamental unit of biology, playing a central role in
the organization and transmission of genetic material. One of the
most striking features of chromosomes is the dynamic behavior they
exhibit throughout the cell cycle. The classic example of chromosome
movement is the segregation of condensed chromatids into the daughter
cells during mitosis. More recently, it has been demonstrated that
decondensed chromatin also exhibits considerable mobility within the
interphase nucleus. This movement has been described as “constrained
diffusion,” in which individual loci execute rapid, random jumps
within a confined region of the nucleus. While this type of
chromatin movement has been characterized in numerous systems, its
relevance to nuclear function remains unclear.
The
focus of this project is to investigate how alterations in chromatin
mobility are related to large-scale transitions in nuclear activity.
This type of regulation may be important during development, as stem
cells transition to a more differentiated state. Thus, we are
particularly interested in examining whether changes in chromatin
mobility correlate with the establishment of distinct cell fates. To
address these questions, we are establishing novel approaches, in the
model organism C. elegans,
to quantitatively measure chromatin dynamics in the early embryo. We
will compare changes in these dynamics between
the cells of different lineages and at successive developmental
landmarks to directly examine the relationship between chromatin
dynamics and cell fate decisions.
Publication
List
Görisch,
S. A., Sporbert, A., Stear, J. H., Grunewald, I., Nowak, D.,
Warbrick, E., Leonhardt, H., Cardoso, M. C. Uncoupling the
replication machinery - replication fork progression in the absence
of processive DNA synthesis. Cell
Cycle. 2008 Jul 1; 7(13):
1983-90.
Brouhard,
G. J.*, Stear, J. H.*,
Nötzel, T. N., Al-Bassam, J., Kinoshita, K. Howard, J. and Hyman A.
A. XMAP215 is a processive microtubule polymerase. Cell.
2008 Jan 11; 132(1): 79-88.
Stear,
J. H., Roth M. B. The C.
elegans kinetochore
reorganizes at prometaphase and in response to checkpoint stimuli.
Mol. Biol. Cell.
2004 Sep 15; 15(11): 5187–5196.
Stear,
J. H., Roth M. B. Characterization of HCP-6, a C.
elegans protein required
to prevent chromosome twisting and merotelic attachment. Genes
Dev. 2002 Jun
15;16(12):1498-508.
