Chromosome-wide regulation is of paramount importance for almost all aspects of biology and for human health. During sexual reproduction, regulated interactions between chromosomes are crucial for chromosome segregation, and for generating the genetic diversity we see around us. Cancers capitalize on disruption of chromosome-wide regulation and the ensuing loss of genome integrity and aberrant gene expression. Despite their importance, many of the organizing principles and molecular mechanisms that underlie chromosome-wide regulation remain mysterious.
Our lab is studying the synaptonemal complex (SC) — a conserved structure that underlies chromosome-wide behaviors during sexual reproduction. The SC has been observed in almost all eukaryotes - from yeast to worms to humans. The structure of the SC has intrigued biologists for decades: it is composed of regular striations that span the interface between perfectly parallel homologous chromosomes. The SC is essential for intimate associations between homologous chromosomes, and it also regulates genetic exchanges. We combine live imaging innovations, biophysical approaches, and emerging technologies to uncover the structure and function of the SC.
We are conducting most of our research in the nematode C. elegans. C. elegans is ideally suited for imaging chromosomes during sexual reproduction, due to its transparent and small body. The C. elegans germline is laid out as a monolayer of hundreds of nuclei, wherein the six chromosome pairs are clearly visible. We have developed novel immobilization methods and fluorescent markers that enable high-resolution imaging.
We harnessed these unique features and technological advances to make the first direct observations of SC assembly in any organism. Live-imaging also allowed us to discover new physical properties of the SC: we showed that despite its ordered appearance, the SC is a liquid-like compartment characterized by mobile subunits and rapid deformations. Our ability to visualize the SC in living animals and to probe it genetically and biochemically positions us to reveal chromosome-wide phenomena at the molecular level.