CAREER: Towards Synthetic Biology in Human Stem Cells

职业：人类干细胞合成生物学

• 批准号: 1350178
• 负责人: Krishanu Saha
• 金额: $ 40万
• 依托单位: University of Wisconsin-Madison
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1350178&HistoricalAwards=false
• 关键词: CAREER; Towards; Synthetic; Biology; Human

CBET-1350178 Saha, KrishanuHuman stem cells provide an attractive, patient-matched source for generating many tissues found in the body, but controlling stem cells in culture remains a key challenge. To meet this challenge, this proposal seeks to develop and apply synthetic biology tools in order to dissect and precisely control the complex molecular signaling processes that determine stem cell behavior in culture. Synthetic biology is an emerging biotechnology field that combines elements of engineering, mathematics, chemistry, and biology to synthesize novel systems from characterized biological components. Applying new synthetic biology tools in human stem cells to control cell behavior would enable advanced manufacturing of patient-specific tissues and cells for disease modeling and drug discovery applications. This proposal outlines a novel approach to convert natural signaling components in human stem cells to synthetic, bioorthogonal ones. The approach relies on producing mutations in cells at defined genomic locations. Such an approach allows for the formation of libraries of mutant cells that can be selected for particular functions. The proposal focuses on a fundamental barrier to establishing a robust stem cell tissue engineering and bioprocessing industry ? manipulating cell signaling pathways when stem cells grow in culture and come together with other cells and materials.The research will be integrated into education by developing and disseminating course modules demonstrating the importance of cross-disciplinary training in stem cell biology, engineering and bioethics for postgenomic approaches to human biomedicine. The proposal to incorporate underrepresented students into the research laboratory and to advance new curriculum will help to develop the next generation of students trained at the stem cell biology-engineering interface.Due to the interdisciplinary nature of the project, this CAREER award by the Biotechnology, Biochemical, and Biomass Engineering Program of the CBET Division is co-funded by the Systems and Synthetic Biology Program of the Division of Molecular and Cellular Biology.

CBET-1350178 SAHA，Krishanuhuman干细胞提供了一种有吸引力的患者匹配的来源，用于产生体内发现的许多组织，但是在培养中控制干细胞仍然是一个关键挑战。为了应对这一挑战，该建议旨在开发和应用合成生物学工具，以剖析和精确控制确定培养中干细胞行为的复杂分子信号传导过程。合成生物学是一个新兴的生物技术领域，结合了工程，数学，化学和生物学的要素，以从特征性的生物学成分中综合新型系统。在人类干细胞中应用新的合成生物学工具来控制细胞行为，将使患者特异性组织和细胞的高级生产用于疾病建模和药物发现应用。 该建议概述了一种新的方法，将人类干细胞中自然信号成分转换为合成生物正交的方法。该方法依赖于在定义的基因组位置的细胞中产生突变。这种方法允许形成可以为特定功能选择的突变细胞的库。该提案重点是建立强大的干细胞组织工程和生物处理行业的基本障碍？当干细胞在培养中生长并与其他细胞和材料融合在一起时，操纵细胞信号通路。该研究将通过开发和传播课程模块来融入教育中，以证明在干细胞生物学，工程和生物eth术中，跨学科培训对于后基因组方法对人类生物医学的重要性。将代表性不足的学生纳入研究实验室并推进新课程的建议将有助于发展在干细胞生物学工程界面上接受培训的下一代学生。项目的跨学科性质，该职业奖，生物技术，生物化学，生物学工程学计划和生物学分区的生物学工程委员会是CBET和同类典型的生物学工程学计划和同步。细胞生物学。

项目成果

High-content imaging with micropatterned multiwell plates reveals influence of cell geometry and cytoskeleton on chromatin dynamics.

• DOI: 10.1002/biot.201400756
• 发表时间: 2015-10
• 期刊: Biotechnology journal
• 影响因子: 4.7
• 作者: Harkness T;McNulty JD;Prestil R;Seymour SK;Klann T;Murrell M;Ashton RS;Saha K
• 通讯作者: Saha K

High-Content Analysis of CRISPR-Cas9 Gene-Edited Human Embryonic Stem Cells

• DOI: 10.1016/j.stemcr.2015.11.014
• 发表时间: 2016-01-12
• 期刊: STEM CELL REPORTS
• 影响因子: 5.9
• 作者: Carlson-Stevermer, Jared;Goedland, Madelyn;Saha, Krishanu
• 通讯作者: Saha, Krishanu

A biodegradable nanocapsule delivers a Cas9 ribonucleoprotein complex for in vivo genome editing

• DOI: 10.1038/s41565-019-0539-2
• 发表时间: 2019-10-01
• 期刊: NATURE NANOTECHNOLOGY
• 影响因子: 38.3
• 作者: Chen, Guojun;Abdeen, Amr A.;Gong, Shaoqin
• 通讯作者: Gong, Shaoqin

Increasing the precision of gene editing in vitro, ex vivo, and in vivo

提高体外、离体和体内基因编辑的精度

• DOI: 10.1016/j.cobme.2018.08.006
• 发表时间: 2018
• 期刊: Current Opinion in Biomedical Engineering
• 影响因子: 3.9
• 作者: Mueller, Katherine;Carlson-Stevermer, Jared;Saha, Krishanu
• 通讯作者: Saha, Krishanu