Total synthesis of the human mammary gland

描述（由申请人提供）：我们对哺乳动物生物学的大部分了解都是从小鼠身上学到的。然而，改善人类健康最终需要更好地了解人类而不是小鼠组织的综合生物学。我们对人类生物学的理解是有限的，因为没有实验上易于处理的系统可用于在复杂的细胞相互作用的背景下研究人体细胞，这是体内组织的特征。该提案通过提出迄今为止结构最复杂和最详细的人体组织模型的合成来解决这一未满足的需求。我们将采取自上而下和自下而上相结合的方法来实现这一目标，使用模块化化学工具来控制3D组织中多种细胞类型的空间组织。我们将重点关注乳腺作为靶器官，因为其具有独特的发育生物学、与人类疾病的相关性以及与模型哺乳动物生物体相比的重要结构差异（Parmar和库尼亚，2004）。大量来自乳腺特有的人体组织的常用和可再生细胞来源也将促进我们的努力。我们努力的完成将为研究人体组织生物学和测试治疗方法提供一个革命性的体外模型。此外，我们从根本上合成的方法将迫使我们挑战关于人体组织的组织和功能的普遍假设，从而揭示这一过程中新的令人兴奋的生物学。在本提案过程中完善的模块化合成策略将适用于许多其他人体组织，最大限度地提高这项工作对更广泛的生物医学界的影响。

DESCRIPTION (provided by applicant): Much of what we know about mammalian biology we have learned from the mouse. However, improvements to human health will ultimately require a better understanding of the integrative biology of human, rather than mouse, tissues. Our understanding of human biology is limited because no experimentally tractable system is available to study human cells in the context of the complex cellular interactions that are characteristic of tissues in vivo. This proposal addresses this unmet need by proposing the synthesis of the most structurally complex and detailed model of a human tissue to date. We will take a combined top-down and bottom-up approach toward this goal, using modular chemical tools to control the spatial organization of multiple cell types in a 3D tissue. We will focus on te mammary gland as the target organ due to its unique developmental biology, relevance to human disease, and important structural differences when compared to model mammalian organisms (Parmar and Cunha, 2004). Our efforts will also be facilitated by a plethora of commonly available and renewable cell sources derived from human tissues that are unique to the mammary gland. Completion of our efforts will provide a revolutionary in vitro model for studying the biology of human tissues and for testing therapeutics. In addition, our fundamentally synthetic approach will force us to challenge commonly held assumptions about the organization and function of human tissues, and will thereby reveal new and exciting biology in the process. The modular synthetic strategies perfected in the course of this proposal will be applicable to many other human tissues, maximizing the impact of this work to the broader biomedical community.