Systemic responses to tissue damage and regeneration

描述（由申请人提供）：本研究的当前目标是表征昆虫损伤后组织再生的全身反应，例如发育延迟，为修复选定组织提供时间。许多组织在损伤后表现出令人印象深刻的修复和再生能力。这在无脊椎动物和脊椎动物组织中可见，甚至在人类子宫内的手指替换中也可见。补偿性生长和再生是动物发育过程中用于替换受损组织的重要过程。对组织损伤和再生的反应包括炎症或邻近细胞的生长减少，以及生长速率的变化，包括发育延迟。对组织损伤的局部反应了解很多，但关于局部信号如何产生全身免疫和发育反应的信息存在空白。昆虫的成虫盘，成虫结构（如翅膀）的前体，显示出特殊的再生能力，当受损时，它们会分泌延迟发育的信号。该项目将（i）描述免疫系统在椎间盘损伤后的反应，（ii）识别和描述从受损椎间盘释放的向内分泌系统提供信号的因子，以及（ii）确定这些血液传播因子对内分泌系统的作用。这项研究将在较大的昆虫Manduca sexta上进行，作为开发遗传上易于控制但较小的果蝇Drosophila melanogaster的互补模式生物的一种手段。鉴于加州大学伯克利分校的Hariharan博士的指导，该试点项目将扩大PI在免疫学和发育方面的专业知识范围，以了解发育如何应对外部压力，以及组织如何相互作用以监测发育过程中生长和体型的变化。它还将提供必要时将果蝇遗传学引入实验室的学习环境。 公共卫生相关性：这项研究拓宽了我们对组织修复的局部反应的理解，着眼于组织损伤的全身效应。许多炎性疾病如囊性纤维化或克罗恩病显示生长和青春期发作的变化，而胰岛素不敏感性是慢性炎症的结果。了解受损组织的信号如何与免疫系统和外周内分泌组织相互作用以改变发育是解决这些问题的关键。最后，这项研究也可能有助于了解癌症治疗过程中X射线引起的损害。

DESCRIPTION (provided by applicant): The current goals of this research are to characterize the systemic responses to tissue regeneration after injury in insects, such as delays in developmental that provide time for the repair of select tissues. Many tissues display an impressive ability for repair and regeneration after injury. This is seen in invertebrate and vertebrate tissues and even in digit replacement in humans in utero. Compensatory growth and regeneration are vital processes used to replace damaged tissue during animal development. Responses to tissue injury and regeneration include inflammation or reduced growth in neighboring cells, as well as changes in growth rate including delays in development. Much is known of the local responses to tissue damage, but there is a gap in information on how local signals produce systemic immune and developmental responses. Insect imaginal discs, the precursors to adult structures such as wings, show exceptional regenerative capabilities, where they secrete signals that delay development when damaged. This project will (i) the characterize responses of the immune system after damage to the imaginal discs, (ii) identify and characterize the factors released from the damaged discs providing signals to the endocrine system, and (ii) determine the actions of these blood-borne factors on the endocrine system. This research will be conducted on the larger insect, Manduca sexta, as a means of developing a complementary model organism to the genetically tractable, but smaller fruitfly, Drosophila melanogaster. Given the mentorship by Dr. Hariharan of UC Berkeley, this pilot project will broaden the scope of the PI's expertise in immunology and development for understanding how development is modulated in response to external stresses, and how tissues interact to monitor changes in growth and body size during development. It will also provide the learning environment for introducing Drosophila genetics to the lab when necessary. PUBLIC HEALTH RELEVANCE: This research broadens our understanding of local responses to tissue repair, looking at the systemic effects of tissue injury. A number of inflammatory diseases such as Cystic Fibrosis or Crohn's display changes in growth and puberty onset, while insulin insensitivity is a result of chronic inflammation. Understanding how signals from damaged tissue interact with the immune system and peripheral endocrine tissues to alter development are key to addressing these problems. Finally, this research may also help understand the damage induced by x-rays during cancer treatments.