Investigating The Functional Role Of Zinc Fluxes During Sperm Activation

研究锌通量在精子激活过程中的功能作用

• 批准号: 9229479
• 负责人: Amanda Rose Bayer
• 金额: $ 3.79万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2018-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9229479
• 关键词: Acrosome; Acrosome Reaction; Affect; Behavioral; Binding; Biological Assay; Biology; Cell Differentiation process; Cell division; Cells; Chelating Agents; Chemistry; Chromatin; Communication; Coupled; Couples; Data; Development; Digestion; Educational workshop; Ejaculation; Environment; Etiology; Event; Fellowship; Female; Female infertility; Fertilization; Fluorescence Microscopy; Fostering; Genetic Transcription; Germ Cells; Goals; Grant; Hormonal; Human; Incubated; Inductively Coupled Plasma Mass Spectrometry; Infertility; Interdisciplinary Study; Ions; Knowledge; Knowledge acquisition; Laboratories; Male Genital Organs; Male Infertility; Maps; Measures; Meiosis; Membrane; Mentors; Metalloproteases; Metalloproteins; Metals; Methods; Microscopy; Molecular; Molecular Biology; Mus; Nanostructures; Nuclear; Outcomes Research; Pathway interactions; Peptide Hydrolases; Physiological; Physiology; Plasma; Play; Positioning Attribute; Postdoctoral Fellow; Property; Protamines; Proteins; Radioactive; Regulation; Reproduction; Research Personnel; Research Project Grants; Roentgen Rays; Role; Schools; Science; Seminal Plasma; Seminal fluid; Signal Transduction; Source; Sperm Capacitation; Sperm Head; Sperm Midpiece; Teaching Method; Techniques; Testing; Testis; Time; Training; United States; Universities; Wood material; Writing; Zinc; Zinc deficiency; career development; cell type; cofactor; egg; enzyme activity; extracellular; frontier; infertility treatment; innovation; insight; male; meetings; men; nuclease; physical science; programs; protein structure; psychologic; public health relevance; reproductive; skills; sperm cell; success; symposium; theories; therapy development; uptake

 DESCRIPTION (provided by applicant): In the United States, as many as one couple in five seeks infertility treatment, with male infertility being the leading cause of half the cases reportd. Understanding the molecular basis for infertility remains a major goal in the search for effective fertility treatments and options. An emerging theory identifies low zinc concentration in seminal plasma as a potential physical source of male infertility; however, the role of intracellular zinc has not yet been identified. The O'Halloran and Woodruff labs recently discovered that spermatozoa accumulate 35 million total zinc atoms to the sperm head and midpiece during capacitation while labile zinc decreases approximately 50% during the first 30 minutes of capacitation. We hypothesize that fluctuations in intracellular zinc concentrations that occur during sperm activation are essential in promoting chromatin compaction and activating protease activity during capacitation. The goal of this fellowship research project is to elucidate the role and mechanism of zinc signaling during sperm capacitation. This goal will be achieved using a combination of physical science, chemistry, and molecular biology approaches. This proposal will determine (a) if the zinc uptake observed during capacitation is essential for activation success; and (b) the molecular mechanism of zinc action during activation on metalloproteins, protease activity, and chromatin compaction. The outcome of this research will provide new insights into zinc signaling in spermatozoa that will aid in the understanding and development of treatment options for male infertility. In addition to an interdisciplinary research program supported by dual mentors in chemistry and reproductive science, this fellowship will provide an opportunity for transdisciplinary training and career development activities. These will include participation in a broad range of professional meetings, new training in teaching methods, and participation in communications skills workshops and grant writing seminars sponsored by The Graduate School at Northwestern. In addition, fellowship support will enable attendance at professional development events outside of Northwestern University, including national academic conferences and laboratory workshops, such as Frontiers in Reproduction at Woods Hole. This fellowship training will enable the applicant to excel professionally and academically at the chemistry:biology interface. In addition, this fellowship will foster an acquisition of the knowledge and professional skills necessary for a successful transition to a post-doctoral fellow position and ultimately as an independent transdisciplinary researcher.

 描述（由申请人提供）：在美国，多达五分之一的夫妇寻求不孕症治疗，其中男性不孕症是报告病例的一半的主要原因。了解不孕症的分子基础仍然是寻找有效的生育治疗和选择的主要目标。一种新兴的理论认为精浆中锌浓度低是男性不育的潜在物理来源，然而，细胞内锌的作用尚未确定。O 'Halloran和Woodruff实验室最近发现，在获能过程中，精子在精子头部和中段积累了3500万个锌原子，而在获能的前30分钟，不稳定的锌减少了约50%。我们推测，在精子激活过程中发生的细胞内锌浓度的波动是必不可少的，在获能过程中促进染色质致密化和激活蛋白酶活性。这个奖学金研究项目的目标是阐明 锌信号在精子获能过程中的作用及机制。这一目标将通过物理科学、化学和分子生物学方法的结合来实现。该提议将确定（a）获能期间观察到的锌摄取是否是活化成功所必需的;以及（B）活化期间锌作用于金属蛋白、蛋白酶活性和染色质压实的分子机制。这项研究的结果将为精子中的锌信号提供新的见解，这将有助于理解和开发男性不育症的治疗方案。除了跨学科的研究 由化学和生殖科学双导师支持的计划，该奖学金将提供跨学科培训和职业发展活动的机会。这些将 包括参加广泛的专业会议，教学方法的新培训，并参加沟通技巧研讨会和西北大学研究生院主办的赠款写作研讨会。此外，奖学金的支持将使在西北大学以外的专业发展活动，包括国家学术会议和实验室研讨会，如生殖前沿在伍兹霍尔出席。该奖学金培训将使申请人在化学：生物学接口方面在专业和学术上表现出色。此外，该奖学金将促进获得成功过渡到博士后研究员职位并最终成为独立的跨学科研究员所需的知识和专业技能。