Haploid gametes, that are essential for sexual reproduction, are generated from diploid precursor cells via meiosis. In females, oocytes undergo 2 major meiosis-specific, cell-cycle transitions whose regulation is poorly understood. The first transition is meiotic resumption where oocytes exit a prolonged prophase arrest and enter the first meiotic M phase (Ml), and the second is the transition between Ml and MIl where homologous chromosomes separate and no round of DNA synthesis occurs. The overall goal of this research proposal is to determine the role of the dual-specificity phosphatase CDC14B during these transitions in mouse oocytes with a long-term goal of establishing an independent research program that focuses on understanding how errors in regulating these transitions are linked to infertility.
The specific aims of this proposal are to test the hypotheses that CDC14B is required to 1) prevent premature meiotic maturation and to 2) regulate the MI-to-MII transition through reversing the actions of the cyclin-dependent kinase, CDK1. The K99 portion of this proposal will be conducted under the mentorship of Dr. Richard Schultz at the University of Pennsylvania. Dr. Schultz has a long-standing interest in oocyte maturation and has mentored many postdoctoral fellows who are now successful independent investigators. Furthermore, the university is committed to training the next generation of scientists. This proposal also describes a detailed plan for the candidate's transition to an independent career including didactic course work and group meetings with a focus on live imaging techniques, a technology the candidate intends on learning in the K99 phase and will continue to use during the R00 phase.
Meiosis is the process that generates eggs and sperm required for sexual reproduction. Female meiosis is highly error-prone in humans;~20% of all eggs contain abnormal chromosome numbers that are linked to spontaneous abortions, stillbirths and developmental diseases like Downs Syndrome. The major goal of this proposal is to determine the role for the CDC14B phosphatase during meiosis in females using the mouse model
| Balboula, Ahmed Z; Stein, Paula; Schultz, Richard M et al. (2015) RBBP4 regulates histone deacetylation and bipolar spindle assembly during oocyte maturation in the mouse. Biol Reprod 92:105 |
| Balboula, Ahmed Z; Stein, Paula; Schultz, Richard M et al. (2014) Knockdown of RBBP7 unveils a requirement of histone deacetylation for CPC function in mouse oocytes. Cell Cycle 13:600-11 |
