Interdisciplinary Research in Contraception and Cancer for Indian Fellows

这一竞争性继续申请要求支持培训三名在印度两家合作机构任职的博士科学家或博士后住院医师[MD或PhD/MD]，从事生殖研究方面的调查工作。重点将放在生殖细胞和分子生物学方面的培训，其中包括针对不孕症的翻译成分，以及发现癌症和避孕药具的新线索。癌症的治疗和诊断可以通过识别肿瘤生物标志物来发展。通过识别在肿瘤中也表达的精子发生的独特基因，可能会确定诊断和药物的新靶点。此外，每两个怀孕中就有一个是意外怀孕，这一事实突出表明全球需要新的避孕选择。部署已知的避孕药具以及推广新的避孕选择是最高优先事项。该培训计划培养生物医学科学家，使他们能够通过研究控制生殖过程的基本机制，识别恢复到配子体途径的肿瘤，认识到这些基础知识为识别候选避孕途径和目标分子提供的机会，从而应对癌症和避孕发现的挑战。并测试新的避孕策略和验证癌症的生物标志物。研究和教学经验是量身定制的，以适应来自不同专业和学术背景的学员。补充课程包括生物统计学、提高写作和沟通技巧的科学英语、重组DNA技术、结构基因组学、药理学、生物伦理学和药物发现、设计、合成和选择。跨学科研究培训是通过与在基础和临床部门任职的导师的互动，通过评估指导和建立避孕措施原则证明的项目，以及通过与工业顾问的合作来实现的。所有导师都在医学院或文理学院担任教职，并指导至少一项活跃的研究经费。通过丰富的研讨会、客座教授、会议和专业研究核心，学院环境促进了互动和交流。主要研究方向包括：精卵融合的分子分析、膜受体之间的信号转导机制、精子获能和顶体反应、蛋白质转录、核转录因子、离子通道的分子生理学、生殖机制的神经内分泌控制、精子发生和卵子发生的分子控制、对精子抗原的自身免疫；附睾精子成熟与昼夜节律。在生殖蛋白的x射线晶体学、配体结合位点的数学建模、新型小分子抑制剂的有机合成以及它们的避孕作用测试方面，教员的专业知识促进了翻译目标的实现。本研究的应用主题包括针对睾丸和附睾中转录因子的男性避孕药的开发，肺和头颈部肿瘤中癌症生物标志物的鉴定，杀精剂的开发，不育诊断以及基于精子和卵子抗原的避孕疫苗。继续对基础科学家、内科医生、泌尿科医生和产科医生进行生殖过程细胞和分子方法的培训，并与肿瘤外科医生建立联系，这符合传统和承诺，即促进美国机构的基础和临床研究人员与印度同行之间的密切联系，促进国际合作和理解。

This competing continuation application requests support to train three PhD scientists or post-resident physicians [MD or PhD/MD], holding positions at two partner institutions in India, for investigative careers in reproductive research. Emphasis will be placed on training in cell and molecular biology of reproduction with translational components aimed at infertility and the discovery of new leads for cancer and contraceptives. Therapies and diagnostics for cancers many be developed through the identification of tumor biomarkers. By identifying unique genes of spermiogenesis that are also expressed in tumors, new targets for diagnostics and drugs may be identified. Further, the global need for new options in contraception is highlighted by the fact that one in every two pregnancies is unwanted. Deployment of known contraceptives as well as advancement of new contraceptive options is a highest priority. This training program develops biomedical scientists who can meet the challenges of cancer and contraceptive discovery by equipping them with the tools to investigate the fundamental mechanisms governing reproductive processes, to identify tumors which revert to the gametogenic pathways, to recognize the opportunities afforded by such basic knowledge for identification of candidate contraceptive pathways and target molecules, and to test novel contraceptive strategies and validate biomarkers for cancer. Research and didactic experiences are tailored to accommodate trainees from diverse professional and academic backgrounds. Supplemental instruction is offered including courses in biostatistics, English for scientific purposes to improve writing and communication skills, recombinant DNA technology, structural genomics, pharmacology, bioethics, and drug discovery, design, synthesis, and selection. Interdisciplinary research training is achieved through interactions with preceptors who hold appointments in basic and clinical departments, through programs that evaluate leads and establish proof of principle of contraceptive action, and through collaboration with industrial advisors. All mentors hold faculty appointments in the School of Medicine or the College of Arts and Sciences and direct at least one active research grant. The institutional environment fosters interaction and exchange through a rich mix of seminars, visiting professors, conferences, and specialized research cores. The broad basic themes of faculty research programs include: the molecular analysis of sperm-egg fusion, signal transduction mechanisms between membrane receptors, sperm capacitation and the acrosome reaction, protein transcription, nuclear transcription factors, molecular physiology of ion channels, neuroendocrine control of mechanisms in reproduction, molecular control of spermatogenesis and oogenesis, autoimmunity to sperm antigens; sperm maturation in the epididymis, and circadian rhythms. Translational aims are fostered by faculty expertise in X-ray crystallography of reproductive proteins, mathematical modeling of ligand binding sites and organic synthesis of new small molecule inhibitors and the testing of their contraceptive action. Applied themes of this research include the development of male contraceptives targeted to transcription factors acting in the testis and epididymis, identification of cancer biomarkers in lung and head and neck tumors, spermicide development, infertility diagnostics, and contraceptive vaccines based on sperm and egg antigens. Continued training of basic scientists as well as internists, urologists, and obstetricians in cellular and molecular approaches to reproductive processes and linkage with oncology surgeons is consistent with the tradition and commitment to foster a close link between basic and clinical investigators at US institutions and their counterparts in India and to facilitate international cooperation and understanding.