Biomimetic cytoskeleton and advanced microscopy to reveal intracellular DNA dynamics and distributions

仿生细胞骨架和先进显微镜揭示细胞内 DNA 动态和分布

• 批准号: 10599773
• 负责人: Ryan McGorty
• 金额: $ 1.69万
• 依托单位: UNIVERSITY OF SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10599773
• 关键词: Biomedical Research; Biomimetics; Biophysics; Circular DNA; Complement; Cytoskeleton; DNA; Doctor of Philosophy; Enrollment; Enzymes; Exhibits; Fellowship; Funding; Goals; Grant; Health; In Situ; In Vitro; Interview; Measurement; Mentors; Mentorship; Microscopy; Molecular Conformation; Pacific Islander; Paper; Parents; Positioning Attribute; Property; Publishing; Research; Research Personnel; Secure; Technical Expertise; Time; Training; United States National Institutes of Health; Universities; Veterans; Work; Writing; career networking; community college; design; experimental study; falls; non-Native; pandemic disease; parent grant; pre-doctoral; programs; skills; undergraduate research; undergraduate student

Project Summary/Abstract The proposed diversity supplement is to support undergraduate researcher, Juexin Marfai, a Pacific Islander non-native English speaker, and Navy veteran who transferred to University of San Diego from community college during the pandemic; and, in turn, to enhance the diversity of the health-related workforce. The proposed supplement to support undergraduate researcher Juexin Marfai will contribute to and advance 2 Aims of our parent R15: (Aim 1) Design in vitro active cytoskeleton networks that exhibit tunable activity for probing non- equilibrium dynamics and rheological properties; and (Aim 2) Determine transport and conformational dynamics of linear and circular DNA within active cytoskeleton networks. The supplement will build on Aim 2, beyond the initial scope of the grant by incorporating in situ enzymatically-driven alterations to the DNA topology. To achieve these goals, we will pursue two Aims: (Aim S1) Perform macrorheology measurements on networks designed in Aim 1 to complement measurements using active and passive microrheology; and (Aim S2) Perform Aim 2 experiments to determine transport and conformational dynamics of DNA molecules with different topologies and which transition their topologies from circular to linear. As an undergraduate researcher, Marfai has developed expertise in preparing and characterizing DNA molecules, quantifying the rheological properties of composites comprised of DNA, and studying how the activity of DNA-cutting enzymes causes time-dependent rheological properties of DNA composites. As a senior undergraduate, Marfai will continue to hone these technical skills while applying them to build upon the Aims of our parent grant. Further, we will focus on training Marfai in a broad range of operational and professional skills which will prepare her to accomplish her goal of earning a MD/PhD to continue in biomedical research. We will work with Juexin Marfai to help her achieve her short-term and long-term goals. Short-term goals include: building her health-related research skillset; broadening her professional network and identifying new mentors; and participating in informational interviews with MD/PhD biomedical researchers. Long-term goals include: publishing 2 more papers on her undergraduate research; securing a postbaccalaureate research position in the PI’s lab or in the lab of one of our collaborators; writing a competitive predoctoral fellowship application (either an F30 or F31 NIH fellowship).

项目总结/摘要 拟议的多样性补充是为了支持本科研究员，太平洋岛民Juexin Marfai， 非英语母语者，从社区转到圣地亚哥大学的海军老兵 在大流行病期间，我们将继续努力提高大学的专业水平;反过来，我们将加强与卫生有关的工作人员队伍的多样性。拟议 补充，以支持本科研究员Juexin Marfai将有助于和推进我们的2个目标 亲本R15：（目的1）设计体外活性细胞骨架网络，其表现出可调的活性，用于探测非- 平衡动力学和流变学性质;以及（目标2）确定运输和构象动力学 线性和环状DNA在活跃的细胞骨架网络。该补编将以目标2为基础， 通过将原位酶促改变纳入DNA拓扑结构，扩大了赠款的初始范围。实现 为了实现这些目标，我们将追求两个目标：（目标S1）在设计的网络上进行宏观流变测量， 目标1，补充使用主动和被动微流变学的测量;和（目标S2）执行目标2 确定具有不同拓扑结构的DNA分子的传输和构象动力学的实验 并且将它们的拓扑结构从环形转变为线性。 作为一名本科生研究员，Marfai在制备和表征DNA方面积累了专业知识 分子，量化由DNA组成的复合材料的流变学性质，并研究如何活动 的DNA切割酶的DNA复合物的时间依赖性的流变特性。作为资深 在本科阶段，Marfai将继续磨练这些技术技能，同时将其应用于 我们的家长格兰特此外，我们将专注于培训Marfai广泛的业务和专业技能 这将使她为实现获得MD/PhD继续从事生物医学研究的目标做好准备。 我们将与Juexin Marfai合作，帮助她实现短期和长期目标。短期目标包括： 建立她的健康相关的研究技能;扩大她的专业网络，并确定新的导师; 并参与与MD/PhD生物医学研究人员的信息访谈。长期目标包括： 发表了2篇关于她本科研究的论文;在大学获得了一个学士后的研究职位。 PI的实验室或在我们的合作者之一的实验室;写一个有竞争力的博士前奖学金申请（无论是 F30或F31 NIH奖学金）。

项目成果

Point-spread function engineering enhances digital Fourier microscopy.

• DOI: 10.1364/ol.42.004603
• 发表时间: 2017-11-15
• 期刊: Optics letters
• 影响因子: 3.6
• 作者: Wulstein DM;McGorty R
• 通讯作者: McGorty R

Myosin-driven actin-microtubule networks exhibit self-organized contractile dynamics.

• DOI: 10.1126/sciadv.abe4334
• 发表时间: 2021-03
• 期刊: Science advances
• 影响因子: 13.6
• 作者: Lee G;Leech G;Rust MJ;Das M;McGorty RJ;Ross JL;Robertson-Anderson RM
• 通讯作者: Robertson-Anderson RM

Topology-dependent anomalous dynamics of ring and linear DNA are sensitive to cytoskeleton crosslinking

• DOI: 10.1126/sciadv.aay5912
• 发表时间: 2019-10
• 期刊: Science Advances
• 影响因子: 13.6
• 作者: Devynn M. Wulstein;Kathryn E. Regan;Jonathan Garamella;R. McGorty;R. Robertson-Anderson

Optical Tweezers Microrheology: From the Basics to Advanced Techniques and Applications.

• DOI: 10.1021/acsmacrolett.8b00498
• 发表时间: 2018-08-21
• 期刊: ACS MACRO LETTERS
• 影响因子: 7.015
• 作者: Robertson-Anderson, Rae M.

Motor-driven advection competes with crowding to drive spatiotemporally heterogeneous transport in cytoskeleton composites

• DOI: 10.3389/fphy.2022.1055441
• 发表时间: 2022-05
• 期刊: Frontiers in physics
• 影响因子: 3.1
• 作者: J. Sheung;Jonathan Garamella;Stella K Kahl;Brian Y. Lee;R. McGorty;R. Robertson-Anderson