Quantitative Cell Biology

定量细胞生物学

• 批准号: CRC-2021-00066
• 负责人: Kafri, Ran
• 金额: $ 7.29万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Canada Research Chairs
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=746543
• 关键词: Quantitative; Cell; Biology

Over decades of research, numerous negative and positive regulators of signal transduction have been identified.?What remains less clear is how these negative and positive regulators converge to specify specific values and magnitudes??In 1975, Nurse and Hartwell postulated that the size of animal cells is determined by cell size checkpoints - molecular mechanisms that?sense cell size?to selectively promote the growth of cells that smaller than their target size. In 2018 - after a gap of almost 50 years - Dr. Kafri, a Canada Research Chair in Quantitative Cell Biology, has identified a molecular signal that is selectively activated in cells that are smaller than `appropriate'. Dr. Kafri's work represents the first molecular mechanism of?size sensing?to have ever been reported in animal cells.? Quantitative phenotypes are not limited to cell size. Just as checkpoint mechanisms function to specify a different and specific cell size for each of the different cell types, there must also be mechanisms that specify a different and specific lifespan value for each of the different mammalian species. How is it that a mouse dies of old age after two years of life while fruit bats live to the age of 40?? Dr. Kafri is aiming to decipher the molecular mechanisms that determine the quantitative phenotypes such as cell size and lifespan. mTORC1 signaling?is known to?promote cellular growth, accelerate aging and?cause?earlier?onset of age-dependent disease, including cancers. Using cutting-edge techniques such as high content screening and computational biology, Dr. Kafri will examine how positive and negative regulators of mTORC1 signaling influence the specific values associated with cell size and lifespan. The questions addressed by Dr. Kafri have a profound impact on human health. It is not age, but rather, age-related diseases that bring about the end of life. By identifying the mTORC1-dependent mechanisms that specify cell size and lifespan, he will identify new drug targets and exploit novel therapeutic approaches for the prevention of old age-related diseases, including the prevention of cancer.

经过数十年的研究，我们已经鉴定出许多信号转导的负调节因子和正调节因子。尚不清楚的是这些负调节因子和正调节因子如何汇聚到特定的值和大小？1975 年，纳斯和哈特韦尔假设动物细胞的大小是由细胞大小检查点决定的，这种分子机制“感知细胞大小”，选择性地促进小于目标大小的细胞生长。 2018 年，时隔近 50 年之后，加拿大定量细胞生物学研究主席 Kafri 博士发现了一种分子信号，该信号在小于“适当”的细胞中被选择性激活。 Kafri 博士的工作代表了在动物细胞中报道的第一个“尺寸传感”分子机制。定量表型不限于细胞大小。正如检查点机制的作用是为每种不同的细胞类型指定不同且特定的细胞大小一样，也必须存在为每种不同哺乳动物物种指定不同且特定的寿命值的机制。为什么老鼠活了两年就老死了，而果蝠却活到了40岁？卡夫里博士的目标是破译决定细胞大小和寿命等定量表型的分子机制。 mTORC1 信号传导已知可促进细胞生长、加速衰老并导致年龄依赖性疾病（包括癌症）提前发生。 Kafri 博士将利用高内涵筛选和计算生物学等尖端技术，研究 mTORC1 信号传导的正负调节因子如何影响与细胞大小和寿命相关的特定值。 卡夫里博士提出的问题对人类健康有着深远的影响。导致生命终结的不是年龄，而是与年龄相关的疾病。通过确定特定细胞大小和寿命的 mTORC1 依赖性机制，他将确定新的药物靶点并开发新的治疗方法来预防老年相关疾病，包括预防癌症。