Detection of Emergent Mechanical Properties of Biologically Complex Cellular States

生物复杂细胞状态的紧急机械特性的检测

• 批准号: 10838854
• 负责人: Mark A LaBarge
• 金额: $ 4.81万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-01 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10838854
• 关键词: Age; Applications Grants; Appointment; BRCA1 gene; BRCA2 gene; Biomedical Engineering; Breast Cancer Risk Factor; Breast Epithelial Cells; Chronology; Communities; Complex; Detection; Development Plans; Devices; Disparity; Dose; Family; First Generation College Students; Genetic; Human; Laboratory Research; MCF10A cells; Machine Learning; Measures; Mechanics; Memory; Mentors; Modeling; Molecular; Non-Malignant; PALB2 gene; Pathway interactions; Predisposition; Recording of previous events; Role; Testing; Variant; Woman; career development; design; doctoral student; experimental study; graduate school; in silico; innovation; malignant breast neoplasm; mechanical properties; older women; parent grant; pre-doctoral; programs; prototype; young woman

Abstract This is a Diversity Supplement to R01EB024989 for the career development of Taylor Thomsen, a first- generation college student who is entering her 2nd-year of graduate school in the UCSF-UC Berkeley Graduate Program in Bioengineering. Thomsen has just joined the Sohn Research Laboratory for her doctoral thesis. The parent grant application pursues the hypothesis that breast cancer risk factors such as age, genetics, and family history integrate through molecular pathways in human mammary epithelial cells (HMECS), resulting in a unique mechanical age in a woman that is distinct from her chronological age. The disparity in mechanical and chronological age measures the susceptibility of a woman’s risk for breast cancer. Under the parent grant, HMEC mechanical properties will be measured using a combination of planar-flow mechano-node-pore sensing (mechano-NPS) and in silico modeling, and mechanical age will be determined through machine learning. Under this Diversity Supplement, Thomsen will develop a new platform—circular mechano-NPS—that will allow her to investigate the mechanical memory of human mammary epithelial cells (HMECs) as they undergo cyclical mechanical dosing. In Aim 1, she will design and prototype the circular mechano-NPS device and test different prototypes using non-malignant MCF10A cells. In Aim 2, she will perform initial mechanical memory experiments with HMEC strains. Ultimately, Thomsen will explore the differences in the mechanical memory of HMECs among young and old women and women who carry who carry germline BRCA1, BRCA2, or PALB2 variants. Mentoring and career development plans for Thomsen are outlined in this supplement, as well as how Thomsen’s appointment promotes diversity within UC Berkeley and the national STEM community. .

抽象的 这是 R01EB024989 的多元化补充，旨在帮助泰勒·汤姆森 (Taylor Thomsen) 的职业发展，泰勒·汤姆森 (Taylor Thomsen) 是第一位 即将进入加州大学旧金山分校-加州大学伯克利分校研究生院研究生二年级的一代大学生 汤姆森刚刚加入索恩研究实验室进行她的博士论文。 家长补助金申请遵循以下假设：年龄、遗传和家庭等乳腺癌风险因素 历史通过人乳腺上皮细胞（HMECS）的分子途径整合，产生了独特的 女性的机械年龄与实际年龄不同。 根据 HMEC 的父母补助金，实际年龄衡量女性患乳腺癌风险的易感性。 机械性能将使用平面流机械节点孔隙传感组合进行测量 （机械-NPS）和计算机建模，机械年龄将通过机器学习确定。 在这份《多样性补充》中，汤姆森将开发一个新平台——圆形机械 NPS——这将使她能够 研究人类乳腺上皮细胞 (HMEC) 在经历周期性变化时的机械记忆 在目标 1 中，她将设计圆形机械 NPS 装置并制作原型并测试不同的装置。 使用非恶性 MCF10A 细胞制作原型 在目标 2 中，她将进行初始机械记忆实验。 最终，汤姆森将探索 HMEC 菌株之间的机械记忆差异。 年轻和老年女性以及携带种系 BRCA1、BRCA2 或 PALB2 变异的女性。 本补充概述了汤姆森的职业发展计划，以及汤姆森如何 这一任命促进了加州大学伯克利分校和全国 STEM 社区的多样性。 。