Detection of Emergent Mechanical Properties of Biologically Complex Cellular States

摘要 这是R01EB024989的多样性补充，用于泰勒·汤姆森的职业发展，这是第一次- 一代大学生，即将进入加州大学伯克利分校研究生院二年级 生物工程专业。汤姆森刚刚加入孙氏研究实验室，完成她的博士论文。这个 父母资助申请追求的假设是乳腺癌的危险因素，如年龄、基因和家庭 历史通过分子途径整合在人乳腺上皮细胞(HMECS)中，导致了独特的 女性的机械年龄与她的实际年龄不同。在机械和机械方面的差距 按时间顺序的年龄衡量了女性患乳腺癌风险的易感性。在母公司的资助下，HMEC 力学性能将使用平面流动机械节点-孔道传感相结合的方法进行测量 (机械-NPS)和计算机建模，机械年龄将通过机器学习来确定。在……下面 这个多样性补充，汤姆森将开发一个新的平台-循环机械-NPS-将使她能够 人乳腺上皮细胞(HMECs)周期性机械记忆的研究 机械给药。在目标1中，她将设计和制作环形机械核动力源装置的原型，并测试不同的 使用非恶性MCF10A细胞的原型。在目标2中，她将进行最初的机械记忆实验 与HMEC菌株进行比较。最终，汤姆森将探索HMEC在机械记忆方面的差异 年轻和老年妇女以及携带生殖系BRCA1、BRCA2或PALB2变种的妇女。辅导 和汤姆森的职业发展计划，以及汤姆森的 任命促进了加州大学伯克利分校和全国STEM社区的多样性。 。

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. .