The exploration of linking RNF20 depended histone H2B ubiquitylation and tumor suppressor gene p53 expression with inflammation and inflammation associated cancer

RNF20依赖性组蛋白H2B泛素化和抑癌基因p53表达与炎症及炎症相关癌症的关系探索

• 批准号: 319465792
• 负责人: Dr. Irina Kerle
• 金额: --
• 依托单位: Department of Molecular Cell Biology
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 无数据
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/319465792?language=en
• 关键词: exploration; linking; RNF20; depended; histone

In my short term fellowship at the laboratory of Professor Moshe Oren at the Department of Molecular Cell Biology of the Weizmann Institute in Rehovot, Israel, I will join a project linking the ligase RNF20 dependent ubiquitylation of histone H2B (H2Bub1) to inflammation and inflammation associated processes in colorectal cancerogenesis. By working with the knock out mouse model RNF20 +/- as well as p53 sequencing I will participate in the further examination of the inflammatory microenvironment and possible linkage of RNF20 depletion with the expression and mutation status of tumor suppressor gene p53. In order to examine the importance of these from mouse model and cell cultures derived findings for colitis and colorectal cancer in human patients I will examine the correlation of p53 expression and mutation status, H2Bub1 and cytokine levels like interleukine 6 and 8 in human colorectal tissue by establishing a H2Bub1 immunhistochemistry protocol and using qRT-PCR from tumor derived RNA of patient samples. My main goal is to learn new lab skills in a field thematically close to my doctoral thesis in a known and well-equipped laboratory such as the Oren lab. By learning these above mentioned lab skills and participating in the group´s performance of whole exome sequencing I will be able to expand my current research projects in the field of free floating tumor DNA detection in plasma and finding mutations that link different tumor entities and inflammatory processes.

作为以色列雷霍沃特魏兹曼研究所分子细胞生物学系Mohe Oren教授实验室的短期研究员，我将加入一个项目，将连接酶RNF20依赖的组蛋白H 2B泛素化(H 2Bub1)与结直肠癌变中的炎症和炎症相关过程联系起来。通过对RNF20+/-小鼠模型的研究以及对P53的测序，我将参与进一步研究炎症微环境以及RNF20缺失与肿瘤抑制基因P53的表达和突变状态之间的可能联系。为了检验这些从小鼠模型和细胞培养中得出的结果在人类结肠炎和结直肠癌中的重要性，我将通过建立H2Bub1免疫组织化学程序并从患者肿瘤样本中使用qRT-PCR来检测人类大肠组织中P53表达和突变状态、H2Bub1和细胞因子水平(如白细胞介素6和8)的相关性。我的主要目标是在奥伦实验室等知名且设备齐全的实验室，在与我的博士论文主题相近的领域学习新的实验室技能。通过学习上述实验室技能并参与S小组的整个外显子组测序，我将能够扩大我目前在血浆中自由浮动肿瘤DNA检测领域的研究项目，并发现将不同肿瘤实体和炎症过程联系在一起的突变。