BRCA1 AND X CHROMOSOME INACTIVATION

描述（由申请人提供）：候选人：Shridar Ganesan的职业目标是成为一名独立的癌症研究人员，专注于乳腺癌的生物学，对BRCA 1肿瘤抑制基因及其参与染色质结构的调节特别感兴趣。 他对乳腺癌发展机制的基础研究将通过他对乳腺癌患者护理的临床参与得到补充。 该霍华德特明奖将协助他过渡到一个完全独立的立场，作为科学调查员和教员。 在接下来的几年里，大卫·利文博士对他的指导对于提高他的研究技能和在BRCA 1生物学领域建立影响力至关重要，从而使他能够顺利过渡到独立的研究职位。 工作环境：丹娜-法伯癌症研究所和哈佛医学院提供了一个良好的环境，为完成本提案中概述的研究目标提供了所需的资源和合作机会。 他的导师利文斯顿博士作为一名优秀的导师有着出色的记录，他的实验室提供了一个激励、支持和富有成效的智力和科学环境。 研究：假设和具体目标是： 假设：BRCA 1与XlST RNA相互作用，并且是适当维持失活X染色体沉默所必需的染色质结构所必需的。 BRCA 1可以与其他RNA种类类似地相互作用，以参与基因组中其他地方的染色质结构的调节。 具体目标： 1.识别和表征BRCA 1和XIST RNA之间的相互作用区域。 2.确定BRCA 1缺失对失活X染色体组蛋白甲基化状态的影响。 3.确定BRCA 1是否与XIST RNA以外的其他RNA相互作用。

DESCRIPTION (provided by applicant): Candidate: Shridar Ganesan's career goal is to become an independent cancer researcher focused on the biology of breast cancer with a specific interest in the BRCA1 tumor suppressor gene and its involvement in the regulation of chromatin structure. This basic research in the mechanism of breast cancer development will be complemented by his clinical involvement in the care of breast cancer patients. The Howard Temin Award will assist his transition to a fully independent position as scientific investigator and faculty member. His mentorship by Dr. David Livinston over the next several years will be critical for refining his research skills and establishing a presence in the field of BRCA1 biology, and thus, allow a smooth transition to an independent research position. Environment: The Dana-Farber Cancer Institute and Harvard Medical School provide an excellent environment with the resources and collaborative opportunities required for the completion of the research goals outline in this proposal. His mentor Dr. Livingston has an outstanding record as an excellent mentor and his laboratory provides a stimulating, supportive, and productive intellectual and scientific environment. Research: The hypothesis and specific aims are: Hypothesis: BRCA1 interacts with XlST RNA and is required for proper maintenance of chromatin structure necessary for silencing of the inactive X chromosome. BRCA1 may interact similarly with other RNA species to participate in regulation of chromatin structure elsewhere in the genome. Specific Aims: 1. Identify and characterize the regions of interaction between BRCA1 and XIST RNA. 2. Determine the effects of BRCA1 loss on the state of histone methylation of the inactive X chromosome. 3. Determine if BRCA1 interacts with other RNA species besides XIST RNA.