NSF/BIO-DFG: Tuning Microtubule-Actin crosstalk to control Mitotic Fidelity

NSF/BIO-DFG：调节微管-肌动蛋白串扰以控制有丝分裂保真度

• 批准号: 2319918
• 负责人: Linda Wordeman
• 金额: $ 48.83万
• 依托单位: University of Washington
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2319918&HistoricalAwards=false
• 关键词: NSF; BIO; DFG; Tuning; Microtubule

Microtubules are relatively long cellular polymers that continuously grow and shrink in a dynamic yet controlled manner. They are also responsible for segregating chromosomes with perfect fidelity during cell division. Previously it has been found that measurable disturbances in dynamic microtubule growth that do not superficially appear abnormal will promote intermittent errors in chromosome segregation through an unknown mechanism. As everyone who owns a car knows, intermittent defects are the most challenging to diagnose. However, strong preliminary evidence indicates that these small changes in microtubule assembly may temporarily promote the delivery of molecules to the cell outer cortex that interfere with the mitotic spindle’s ability to position itself in space. This, in turn, increases the rate that cells make errors during cell division. Describing this biological phenomenon will prove important to understand the regulation of growth and development in both plants and animals. The Broader Impacts of the work includes its intrinsic merit as all dividing eukaryotic cells employ microtubes for division. Moreover, errors in the process can result in a variety of human maladies. Additional activities include the training of undergraduate and graduate students in research methods and incorporation of the research into an existing course.This project will employ high resolution live imaging, atomic force microscopy and actin reporters to catch mitotic spindles “in the act” of temporarily losing spatial positioning during controlled experimental alteration of microtubule growth rates. A custom method of quantifying attachment errors using super-resolution expansion microscopy will be employed to directly correlate the number of segregation errors commensurate with spindle orientation. The project includes developmental systems to determine the extent to which these mechanisms, initially described in cell culture, are utilized during normal development and in the establishment of tissue architecture.This collaborative US/German project is supported by the US National Science Foundation (NSF) and the Deutsche Forschungsgemeinschaft (DFG) where NSF funds the US investigator and DFG funds the German partner.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

微管是相对较长的细胞聚合物，以动态但受控的方式连续生长和收缩。他们还负责隔离细胞分裂期间具有完美忠诚度的染色体。以前已经发现，没有超级出现异常的动态微管生长的可测量干扰会通过未知机制促进染色体隔离的间歇性误差。众所周知，所有拥有汽车的人都知道，间歇性缺陷是诊断最大的挑战。但是，有力的初步证据表明，这些微管组装中的这些小变化可能会暂时促进分子向细胞外皮层的递送，从而干扰有丝分裂纺锤体在太空中定位的能力。反过来，这增加了细胞在细胞分裂过程中造成误差的速率。描述这种生物学现象将被证明对了解动植物的生长和发育的调节很重要。这项工作的更广泛的影响包括其内在优点，因为所有分裂的真核​​细胞都采用微管进行分裂。此外，此过程中的错误可能导致各种人类疾病。其他活动包括在研究方法和研究法规中培训本科和研究生的现有课程。该项目将采用高分辨率的实时成像，原子力显微镜和肌动蛋白记者来捕获暂时损耗空间定位的有丝分裂纺锤体，这是微管生长速率的受控实验改变。将使用超分辨率扩展显微镜量化附件误差的自定义方法，以直接将隔离误差的数量与纺锤体方向相称。 The project includes developmental systems to determine the extent to which these mechanisms, initially described in cell culture, are utilized during normal development and in the establishment of tissue architecture.This collaborative US/German project is supported by the US National Science Foundation (NSF) and the Deutsche Forschungsgemeinschaft (DFG) where NSF funds the US investigator and DFG funds the German partner.This award reflects NSF's法定使命，并使用基金会的知识分子优点和更广泛的影响标准通过评估被认为是宝贵的支持。