SysCODE: Systems-based Consortium for Organ Design and Engineering

项目摘要 对器官及其组成部分的永久性损害是人类发病的主要原因。而 器官再生的需求部分通过移植和生物工程材料和装置来解决， 发展一种系统的方法来制造新的器官和器官部分将改变医学。 然而，目前还没有一个统一的学科， 调节网络，祖细胞和组织工程到一个系统的，非经验性的框架， 可以在体外合成器官。尽管它们的功能不同，许多哺乳动物的器官 通过共同的机制发展，这些机制涉及到信号之间的顺序，有序的交换， 相互作用的细胞群，导致其进行性分化。我们假设这个复合体， 作为内源性器官发育基础的动态调节网络可以在遗传学上得到解决。 并最终在分子水平上通过不同科学学科的整合， 可以以“分子蓝图”的形式用于设计和构建器官前体和部件。 器官设计与工程系统联盟（Systems-based Consortium for Organ Design and Engineering，SysCODE）将专注于 三种小鼠器官成分的合成：牙胚、胰岛和心脏瓣膜。这些 发育中的组织既代表了复杂性的分级水平， 生理和动力学特性。为了实现这一宏伟目标，联合会将要求 形成新的交叉学科，这些学科位于发育生物学、计算生物学和生物学之间的节点。 基因组科学和组织工程。为此，我们招募了24位杰出的科学家， 哈佛及其附属医院、麻省理工学院、范德比尔特和波士顿大学， 他们有着共同的愿景，即作为一个综合科学团队共同努力， 这个令人信服的目标。这个U 54领导和管理模块描述了器官的巨大挑战 工程，科学和行政组成部分，这个财团现在已经组装，以满足 挑战，以及该联盟将如何做到这一点的战略计划。该联盟将领导 发展跨学科科学的新范式，并以一种 改变医学

Project Summary Permanent damage to organs and their constituent parts is a major cause of human morbidity. While the need for organ regeneration is partly addressed by transplantation and bioengineered materials and devices, the development of a systematic method to generate new organs and organ parts would transform medicine. At present, however, there is no unified discipline that integrates knowledge about organogenesis, gene regulatory networks, progenitor cells and tissue engineering into a systematic, non-empiric framework that can be used to synthesize organs in vitro. Despite their different functions, many mammalian organs develop by common mechanisms that involve the sequential, ordered exchange of signals befween interacting cell populations, resulting in their progressive differentiation. We hypothesize that the complex, dynamic regulatory networks that underlie endogenous organ development can be resolved at the genetic and ultimately molecular level by the integration of different scientific disciplines, and that this information can be used in the form of a "molecular blueprint" to design and build organ precursors and parts. The Systems-based Consortium for Organ Design and Engineering (SysCODE) will focus on the synthesis of three murine organ components: the tooth germ, pancreatic islet and heart valve. These developing tissues represent both graded levels of complexity and the acquisition of distinct mechanical, physiologic and dynamic properties. To accomplish this ambitious goal, the Consortium will require the formation of new interdisciplines that lie at the nodal points between developmental biology, computational and genome science, and tissue engineering. To this end, we have recruited 24 exceptional scientists from Harvard and its affiliated Hospitals, MIT, Vanderbilt and Boston University who encompass the necessary expertise and who share a common vision of working together as an integrated scientific team to achieve this compelling goal. This U54 Leadership and Management Module describes the grand challenge of organ engineering, the scientific and administrative components that this Consortium has now assembled to meet the challenge, and the strategic plan for how this Consortium will do so. This Consortium will lead in the development of a new paradigm for interdisciplinary science, and build organ'parts in a way that will transform medicine.