Molecular regulation of Insulin signaling in nutrient stress response in Drosophila.

器官生长是后生动物发育过程中最基本的生物学过程之一，受到多种机制的严格调控。决定果蝇成虫大小的一个关键因素是幼虫生长阶段的营养供应。营养减少会减少幼虫的生长，最终会减少成年苍蝇的大小。这项研究项目旨在了解动物如何根据营养的可获得性来调整它们的生长速度。这将为动物发育过程中潜在的营养应激反应的分子机制提供新的见解。此外，该项目将提供一个平台，扩大在STEM领域任职人数不足的学生在多个层次上的参与。这项研究的结果将被整合到本科生和研究生的研讨会、研讨会和课程中，这将激励未来的学生在生物研究方面追求教育和职业生涯。胰岛素信号通路在控制细胞生长、增殖和代谢以响应细胞内和细胞外刺激方面发挥着关键作用。在果蝇中，PTEN突变细胞在营养饥饿条件下表现出很强的生长优势。值得注意的是，PTEN突变眼球大小的增加主要是由于营养丰富条件下细胞体积的增大，而PTEN突变眼球在营养饥饿条件下的过度生长主要是由于细胞数量的大量增加。营养减少主要是如何影响PTEN突变细胞的增殖能力尚不清楚。果蝇头壳是一种营养应激特异性生长调节剂，调节细胞周期进程。HDC在基因上与多种胰岛素信号通路成分相互作用。此外，HDC蛋白被Akt磷酸化，Akt是胰岛素信号通路的关键蛋白激酶。这个项目的中心假设是HDC作为胰岛素信号通路的一个新的下游调节因子，介导PTEN调节的营养应激反应。这一假说将通过三个特定的目的得到验证：(1)确定将营养状况与HDC生长抑制功能联系起来的上游信号；(2)研究Akt诱导的HDC磷酸化的分子调控；(3)确定HDC在PTEN介导的营养应激反应中的作用。这项拟议的研究有望揭示营养应激反应中胰岛素信号通路的新的分子结构。该项目将为STEM领域中代表性不足的学生提供一个扩大参与的平台。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Organ growth is one of the most fundamental biological processes during metazoan development and is tightly regulated by multiple mechanisms. A key factor that determines adult size in the fruit fly Drosophila is nutrient availability during the larval growth phase. Reduced nutrition decreases larval growth, and eventually the final size of an adult fly. This research project aims to understand how animals adjust their growth rate in response to nutrient availability. It will provide new insights into the molecular mechanisms underlying nutrient stress response during animal development. In addition, this project will provide a platform for broadening participation of students under-represented in STEM fields at multiple levels. The results of this research will be integrated into workshops, seminars, and courses for undergraduate and graduate students, which will inspire prospective students to pursue education and careers in biological research.The insulin signaling pathway plays critical roles in controlling cell growth, proliferation and metabolism in response to intracellular and extracellular stimuli. In Drosophila, PTEN mutant cells showed a strong growth advantage under nutrient starvation conditions. Strikingly, while the increase of PTEN mutant eye size was mainly caused by enlarged cell size under nutrient rich conditions, the overgrowth of the PTEN mutant eye under nutrient starvation conditions was largely due to massively increased cell number. How reduced nutrition primarily affects the proliferation potential of PTEN mutant cells remains unclear. Drosophila Headcase (Hdc) is a nutrient stress specific growth regulator that regulates cell cycle progression. Hdc genetically interacts with multiple insulin signaling pathway components. In addition, Hdc protein is phosphorylated by Akt, a key protein kinase of the insulin signaling pathway. The central hypothesis of this project is that Hdc functions as a novel downstream regulator of the insulin signaling pathway and mediates PTEN regulated nutrient stress response. This hypothesis will be tested by three specific aims: (1) define the upstream signal that links nutritional status to Hdc growth inhibition function, (2) investigate the molecular regulation of Hdc by Akt induced phosphorylation, and (3) determine the role of Hdc in PTEN mediated nutrient stress response. The proposed research is expected to reveal novel molecular architecture of the insulin signaling pathway in nutrient stress response. This project will provide a platform for broadening participation of students that are under-represented in STEM fields.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.