Public Health Relevance

Fertilization is biological process with important medical, social and economic implications. From extensive study, the events of fertilization are known in some detail. However, the molecular underpinnings of these events generally remain elusive. Most previous work on fertilization has relied on biochemical and immunological approaches. Our work is groundbreaking in the application of classic gentic analsysis to this vital area of research. RATIONALE: Many of the genetic and molecular tools developed for C. elegans are not available or are very difficult to utilize in other organisms traditionally used for studying fertilization. One of the most significant advantages of C. elegans is the ability to isolate and maintain mutants that affect sperm or eggs and no other cells. Previously, through the study of sterile mutants, we have identified some of the first molecules required for productive gamete interactions in C. elegans.
We aim to get a better understanding how sperm molecules (SPE-9, SPE-38, SPE-41/TRP-3 and SPE- 45/Izumo) and oocyte molecules (EGG-1/2) functions to insure successful fertilization. The SPE-45/Izumo gene represents a conserved sperm function from worms to humans. Futher, a full understanding of the molecular mechanisms of fertilization is impossible without a more complete inventory of molecular components. Therefore we aim to identify new fertilization molecules through genetic and molecular analysis. Particular emphasis will be placed on the identification of genes required in oocytes. OBJECTIVES: The goal of this proposal is to further our understanding of fertilization in C. elegans by conducting the following experimental aims: 1) Determine the molecular nature of new gamete function genes defined by a fertilization defective mutant phenotype. 2) Investigate mechanistic connections, functions and fertilization pathways of previously identified gamete function molecules. 3) Conduct a saturation mutagenesis for fertilization mutants taking advantage of an innovative genetic screening strategy that enriches for gamete function mutants. This work will complement fertility studies in other organisms as well as provide insights into the mechanisms of cell-cell interactions and the diversity of reproductive strategies.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
2R01HD054681-11A1
Application #
8641865
Study Section
Cellular, Molecular and Integrative Reproduction Study Section (CMIR)
Program Officer
Moss, Stuart B
Project Start
2001-05-01
Project End
2018-10-31
Budget Start
2013-11-25
Budget End
2014-10-31
Support Year
11
Fiscal Year
2014
Total Cost
$321,625
Indirect Cost
$114,125
Name
Rutgers University
Department
None
Type
Organized Research Units
DUNS #
001912864
City
New Brunswick
State
NJ
Country
United States
Zip Code
08901
Krauchunas, Amber R; Marcello, Matthew R; Singson, Andrew (2016) The molecular complexity of fertilization: Introducing the concept of a fertilization synapse. Mol Reprod Dev 83:376-86
Singaravelu, Gunasekaran; Rahimi, Sina; Krauchunas, Amber et al. (2015) Forward Genetics Identifies a Requirement for the Izumo-like Immunoglobulin Superfamily spe-45 Gene in Caenorhabditis elegans Fertilization. Curr Biol 25:3220-4
Singaravelu, Gunasekaran; Singson, Andrew (2013) Calcium signaling surrounding fertilization in the nematode Caenorhabditis elegans. Cell Calcium 53:2-9
Marcello, Matthew R; Singaravelu, Gunasekaran; Singson, Andrew (2013) Fertilization. Adv Exp Med Biol 757:321-50
Chatterjee, Indrani; Ibanez-Ventoso, Carolina; Vijay, Priyanka et al. (2013) Dramatic fertility decline in aging C. elegans males is associated with mating execution deficits rather than diminished sperm quality. Exp Gerontol 48:1156-66
Singaravelu, Gunasekaran; Chatterjee, Indrani; Rahimi, Sina et al. (2012) The sperm surface localization of the TRP-3/SPE-41 Ca2+ -permeable channel depends on SPE-38 function in Caenorhabditis elegans. Dev Biol 365:376-83
Marcello, Matthew R; Singson, Andrew (2011) Germline determination: don't mind the P granules. Curr Biol 21:R155-7
Singaravelu, Gunasekaran; Chatterjee, Indrani; Marcello, Matthew R et al. (2011) Isolation and in vitro activation of Caenorhabditis elegans sperm. J Vis Exp :
Singaravelu, Gunasekaran; Singson, Andrew (2011) New insights into the mechanism of fertilization in nematodes. Int Rev Cell Mol Biol 289:211-38
Geldziler, Brian D; Marcello, Matthew R; Shakes, Diane C et al. (2011) The genetics and cell biology of fertilization. Methods Cell Biol 106:343-75

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