Cellular and Molecular Tumorsuppressor Processes Uncovered by DNA Fork Protection

申请人Katharina Schlacher致力于终身学术生涯，旨在成为复制叉保护领域癌症研究前沿的独立研究者和导师。卡塔琳娜提出了三年计划，这将使她在这个充满挑战的资金环境中成为一名成功的独立研究调查员。该项目旨在研究肿瘤抑制因子保护复制叉的细胞和分子过程。该项目的具体目标如下：目的1研究肿瘤细胞中复制叉的不稳定性， 目的2测试FA介导的复制体稳定性，和目的3确定在叉保护过程中的RAD 51旁腺肿瘤抑制因子功能。拟议的目标将获得关于这一新的研究领域对肿瘤生物学的影响的关键知识，了解其在肿瘤细胞中的作用，并启动对叉保护的详细见解。这个项目将加强她的能力和这个新的研究领域，这是她独立职业生涯的核心，在此期间，她渴望破译复制叉保护的机制，确定这一途径的新参与者，并打开大门，了解其对干细胞生物学和治疗策略的影响。候选人将定期与导师会面，与该领域的其他相关专家互动，并通过结构化会议，会议和课程来补充她的培训。该奖项将产生足够的初步数据为独立的资金申请，并使她能够获得关键的技术知识，经验和数据需要建立和充实这个新的研究领域，成功地启动她的独立职业生涯，并确保独立的教师职位在健康相关的研究。她将在IPOND，Rad51旁系同源物和Talen基因组工程技术以及乳腺，卵巢和胰腺肿瘤细胞中的复制叉不稳定性方面获得关键的额外和补充经验。Schlacher博士和她的导师因此认为这个项目是一个关键的机会，使她能够满足她的研究目标和愿望的挑战。

DESCRIPTION (provided by applicant): The applicant, Katharina Schlacher, is committed to a lifelong academic career and aims to become an independent investigator and enabling mentor at the frontier of cancer research in the field of replication fork protection. Katharina proposes three-year plan that will optimally equip her to becoming a successful independent research investigator in this challenging funding environment. The proposed project seeks to study cellular and molecular processes of replication fork protection by tumor-suppressor. The specific aims of the project are as follows: Aim1 Investigating replication fork instability in tumor cells, Aim2 Testing FA-mediated replisome stability, and Aim3 Determining RAD51 paralog tumor suppressor functions during fork protection. The proposed Aims will obtain critical knowledge on the impact of this new area of research to tumor biology, to understand its role in tumor cells and to initiate detailed insights into fork protection. This project will strengthen her abilities nd this new research area that is at the heart of her independent career, during which she aspires to decipher the mechanism of replication fork protection, identify new players of this pathway and open doors to understanding its implications with regards to stem cell biology and therapeutic strategies Under the mentorship of Dr. Maria Jasin (MSKCC) and co-mentor Dr. Hong Wu (UCLA), the candidate will meet regularly with her mentors, interact with other pertinent experts in the field, and supplement her training with structured meetings, conferences, and coursework. The award will produce sufficient preliminary data for independent funding applications, and enable her to acquire key technical knowledge, experience, and data needed to build and substantiate this new research area, to successfully jump-start her independent career and to secure an independent faculty position in health-related research. She will gain key extra and complementary experience in IPOND, Rad51 paralogs, and Talen technology for genomic engineering as well as on replication fork instability in mammary, ovarian and pancreatic tumor cells. Dr. Schlacher and her mentors thus view this project as a critical enabling opportunity for her to meet the challenges of her research goals and aspirations.