Human Endogenous Retroviral Sequences, a Tool to Study the Role of Centromeres in

描述(申请人提供)：拟议的K22申请“人类内源性逆转录病毒序列，一种研究着丝粒在人类癌症中的作用的工具”将研究人类基因组着丝粒中的内源性逆转录病毒序列，目前世界基因组数据库中还没有这些序列，并将开发着丝粒序列标记，以了解着丝粒在癌症中的作用。具体地说，候选人将对人类着丝粒中的内源性逆转录病毒进行测序和表征，并发现可用作着丝粒标记的信息丰富的DNA替代。此外，还将评估这些标记物在确定着丝粒在乳腺癌以及白血病/淋巴瘤中所起作用方面的适用性。因此，常规和深度测序方法将被用来识别与癌症相关的着丝粒标记的突变。这些信息可以开始为理解每个染色体着丝粒所起的作用提供基因组基础，并可能导致改进研究遗传缺陷和癌症的方法。这位候选人获得了生物医学博士学位，主修病毒学，目前是密歇根大学研究人类内源性逆转录病毒的博士后研究员。候选人的最终职业目标是成为一名独立科学家，研究人类基因组中内源性逆转录病毒序列在艾滋病毒感染、遗传病和癌症生物学中的作用。为了确保这项提议的成功和他在转译癌症研究方面的职业发展和向独立的过渡，这位候选人将自己置于密歇根大学的支持性研究环境中，那里有大量世界领先的资深癌症研究人员，他们使用下一代测序分析和基因组以及生物信息学方法来研究癌症和人类遗传学。认识到候选人的癌症生物学背景的局限性，他的职业发展计划的关键要素包括参加生物信息学和癌症生物学的课程和研讨会，并在这些领域获得进一步的实验和计算培训。拟议的培训将极大地促进候选人的科学发展，并将极大地帮助他 在实现他的最终目标--实现研究的独立性方面。

DESCRIPTION (provided by applicant): The proposed K22 application "Human Endogenous Retroviral Sequences, a Tool to Study the Role of Centromeres in Human Cancer" will investigate the sequences of endogenous retroviruses in the centromeres of the human genome, which are currently unavailable in the world's genome databanks, and will develop centromere sequence markers to understand the role centromeres play in cancer. Specifically, the candidate will sequence and characterize endogenous retroviruses in human centromeres and discover informative DNA substitutions that can be used as centromere markers. In addition, the applicability of these markers in determining the role centromeres play in breast cancer, as well as leukemia/lymphoma will also be evaluated. Hence, conventional and Deep-sequencing approaches will be used to identify mutations in the centromere markers associated with cancer. This information could begin to provide the genomic foundation for understanding the role each chromosomal centromere plays, and could potentially result in improved methodologies for studying genetic defects and cancer. The candidate earned his Ph.D. In Biomedical Sciences with a concentration in Virology and is currently a postdoctoral fellow at the University of Michigan studying human endogenous retroviruses. The candidate's ultimate career goal is to become an independent scientist investigating the role endogenous retroviral sequences in the human genome play in HIV infection, genetic diseases, and cancer biology. To ensure success with this proposal and his career development and transition to independence in translational cancer research, the candidate has placed himself in a supportive research environment at the University of Michigan, rich in senior world leader cancer investigators who use next generation sequencing analysis and genomic, as well as bioinformatics approaches in the study of cancer and human genetics. Recognizing the limitation of the candidate's cancer biology background, key elements of his career development plan includes enrolling in courses and seminars in Bioinformatics and Cancer biology and obtaining further experimental and computational training in these areas. The training proposed will contribute substantially to the candidate's scientific development and will greatly assist him in attaining his ultimate goal of achieving independence in research.