Our lab is interested in
meiosis, the special division process by which the genetic information
on chromosomes is transmitted from parent to progeny through sexual
reproduction. Errors in this process lead to aneuploidy and are a major
cause of human birth defects such as Down syndrome. We are investigating
how chromosomes are reorganized during this unique cell cycle by
combining high-resolution imaging of chromosomes in situ and in vivo
with the molecular genetic advantages of C. elegans. A
fundamental goal of our work is to understand how specific DNA sequences
confer not only gene expression patterns but also the large-scale
3-dimensional organization of the genome.
Project #1: Dissecting the function of meiotic pairing centers
When most people think of genomics, they often consider only the portion of the genome containing protein coding and expression information. My group is interested how information encoded within the genome controls global chromosome architecture and mediates interactions between chromosomes and other components of the cellular machinery. In all eukaryotes, simple, repetitive sequence elements play major roles in chromosome structure and inheritance functions. For example, work in a variety of organisms has elucidated the behavior of centromeres and telomeres, two types of sites containing noncoding sequences with fundamental roles in chromosome organization and function. We are exploring the function of another type of cisacting site that is much more poorly understood: meiotic pairing centers. In C. elegans, these specific sites on each of the six chromosomes are essential for meiotic recombination and accurate segregation.
New tools for understanding noncoding DNA sequences have
become available through genome sequencing efforts. C. elegans is
unusual in that its genome assemblies now include virtually all of the
so-called "junk DNA" - the simple-sequence repetitive elements, or
heterochromatin. Through bioinformatics, we have identified a unique
repetitive element whose genomic distribution corresponds precisely with
the location of meiotic pairing centers, and we are currently testing
whether this sequence can mediate homologous interactions during
meiosis. Using classical and reverse genetics, we have also identified a
number of genes that interact with the Pairing Centers, and we are
working to understand how their encoded proteins contribute to the
function of these sites.
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Project #2: Meiotic chromosome dynamics in vivo
A major goal of our lab is to understand how
the biophysical properties of chromosomes are modulated during meiosis,
and how these properties control behaviors such as homolog pairing and
recombination. Because C. elegans is optically transparent, we
can observe these dynamic events as they occur in living animals. We
have recorded large-scale chromosome movements during the stages of
homolog pairing and synapsis using high-resolution 4-dimensional
imaging. We are identifying the molecules driving this movement, and
developing methods to describe these dynamics quantitatively. A key goal
for the future is to implement automated methods to extract information
from complex 4-D images.
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