Gamete Interactions in Caenorhabditis elegans

Project Details

Description

DESCRIPTION: (provided by applicant)
Fertilization is a cell biological process with important medical, social and
economic implications. The underlying cell biological functions of gamete
interactions are conserved in all cells regardless of their somatic or
germ-line origins. Despite intense study, sperm-egg interactions are still
poorly understood at the molecular level. Most previous work on fertilization
has relied on biochemical and immunological approaches while a genetic approach
has been lacking.

We are pioneering the use of the nematode worm Caenorhabditis elegans for
addressing the molecular mechanisms of sperm-egg interactions. The powerful
tools of classical and molecular genetics developed for the worm are not
available or are very difficult to utilize in the other organisms traditionally
used for studying fertilization. The reproductive biology of C. elegans
facilitates the identification of mutations that affect sperm and no other
cells. These mutations provide a unique opportunity to define sperm components
required for sperm-egg interactions. Worms with mutations in two interacting
genes, spe-9 and spe-13, produce spermatozoa with wild-type morphology and
motility that cannot fertilize oocytes even after contact between gametes.
Therefore, disruption of spe-9 or spe-13 function affects either gamete
recognition, adhesion, signaling and/or fusion. The spe-9 gene encodes a sperm
transmembrane protein with an extracellular domain that contains ten epidermal
growth factor (EGF)-like repeats. A common feature of proteins that include
EGF-like motifs is their involvement in extracellular functions such as
adhesive and ligand-receptor interactions. These results are consistent with
the hypothesis that SPE-9 functions in the specialized cell-cell interactions
required for fertilization.

In order to more precisely define the role of SPE-9 during fertilization, we
will determine its localization in sperm and reveal the cellular regions
important for gamete interactions. Furthermore, we will investigate how
different domains of the protein contribute to its biological function. We will
clone the spe-13 gene and analyze its gene product. This information will be
useful in formulating a molecular model concerning the role of SPE-13 during
fertilization and possible interactions with SPE-9. We will initiate the
characterization of several new genes that when mutated appear to phenocopy the
spe-9 and spe-13 mutations. Such genes are expected to encode additional sperm
components required for fertilization. Finally, we will conduct genetic screens
to identify the oocyte receptor for SPE-9 and other genes required for
sperm-egg interactions. This work will provide new insight into cell-cell
interactions, conception and complement studies of fertilization in other
organisms.
StatusFinished
Effective start/end date5/1/014/30/07

Funding

  • National Institute of General Medical Sciences: $248,880.00
  • National Institute of General Medical Sciences: $227,005.00
  • National Institute of General Medical Sciences: $227,005.00
  • National Institute of General Medical Sciences: $227,005.00
  • National Institute of General Medical Sciences: $227,005.00

ASJC

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Genetics
  • Molecular Biology

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.