IDBR: A workstation for optogenetics in embryogenesis and regeneration
IDBR:胚胎发生和再生中的光遗传学工作站
基本信息
- 批准号:1152279
- 负责人:
- 金额:$ 69万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Continuing Grant
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-02-01 至 2016-01-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The orchestration of cell behavior into multicellular pattern formation is a central issue for developmental, regenerative, cancer, evolutionary, and synthetic biology. Molecular and cell biology has made remarkable strides because tools were developed for the experimental control of biochemical signals. However, Bioelectric signals - a fascinating and important physical layer of pattern control - remain poorly understood. Functional experiments using targeted, quantitative, molecular-level changes in ion fluxes in a variety of vertebrate and invertebrate model systems implicated specific bioelectric events in development (left-right asymmetry, craniofacial patterning, eye induction), regeneration (tail and limb regeneration in vertebrates, and anterior-posterior polarity in planaria), and is now being applied to detection and suppression of cancer in situ. By developing 1) tools that allow molecular-level changes in physiological properties in vivo, 2) building quantitative computer models synthesizing physiological and molecular data, 3) fleshing out pathways that show in detail how biophysical signals are produced, propagated, and transduced into downstream canonical biochemical/transcriptional responses, and 4) disseminating protocols and reagents to many labs in related fields, bioelectricity has been brought into a new age. Crucially, the field is held back by a lack of tools: transformative impact requires the ability for many labs to be able to exert tight spatio-temporal control over ion flux and transmembrane voltage in vivo. Optogenetics (expression of light-sensitive ion channels) is an exciting advance, but has never been applied outside of excitable cells (nerve and muscle) because available devices do not allow flexible control of sufficiently-bright light delivered over large areas - a necessity when working with developing or regenerating systems (organs, whole animals, or bioengineered constructs). This project will develop an automated, highly versatile, optogenetics research station that extends past existing technology to enable experimental control of voltage gradients in model systems. Built around a computer controlled microscope that is suitable for working with anything from small animals to individual cells, this platform will allow any lab that has access to molecular biology and microscopy to perform screens and targeted experiments on the role of physiology and bioelectricity in any context. This will significantly impact several basic fields by transforming the state of the art in how functional in vivo physiology experiments are planned, executed, and analyzed. Aim 1 capitalizes on commercial partnerships and local collaborators in engineering and optics to build a platform for light-based control of resting potential in any desired cell groups. Aim 2 validates the system by proof-of-principle applications in the control of stem cell derivatives in vivo and regulation of organ patterning in the Xenopus laevis system.Crucially, protein/mRNA profile does not fully determine cell behavior; this IDBR platform will transform the field of functional electrophysiology, and help to crack the bioelectrical code, by, for the first time, allowing many labs to easily collect functional physiomic data. Direct control of voltage in any cell/tissue of interest will enable quantitative understanding of how biophysical (post-translational) parameters interact with gene regulatory networks in determining pattern formation and tissue/organ function. Bringing a whole new aspect of regulation to several communities will allow the field to truly understand the role and information content of biophysical gradients.The proposed activity will involve the training of a minority PhD student and talented young post-doctoral fellow in highly interdisciplinary techniques at the forefront of developmental biology, at the collaborative edge between basic science and engineering industry. Natural bioelectric fields form a kind of subtle "scaffold" that determines the growth and form of biological structures, and guides the activity of gene networks. The ability for any lab to control the natural bioelectric fields inside living tissues will transform our ability to understand and control the shape of tissues and organs. This will have important implications for understanding evolution of complex body parts, as well as ultimately driving novel the synthetic biology and bioengineering applications. The direct beneficiaries of this technology will be not only the undergraduates and other students who will use such devices in state-of-the-art learning modules, but society as a whole, which will ultimately benefit from applications of this technology to biomedicine (bioengineering of organs in vitro, regenerative sleeves, and development of robust computational devices made of living tissues).
将细胞行为编排成多细胞模式形成是发育、再生、癌症、进化和合成生物学的中心问题。 分子和细胞生物学已经取得了显着的进步,因为工具的开发,实验控制的生化信号。然而,生物电信号--模式控制的一个迷人而重要的物理层--仍然知之甚少。在各种脊椎动物和无脊椎动物模型系统中,使用有针对性的,定量的,分子水平的离子通量变化的功能实验涉及发育(左右不对称,颅面图案,眼睛诱导),再生(脊椎动物的尾巴和四肢再生,以及前-后极性的涡虫)中的特定生物电事件,现在正被应用于原位癌症的检测和抑制。通过开发1)允许体内生理特性的分子水平变化的工具,2)建立合成生理和分子数据的定量计算机模型,3)充实详细显示生物物理信号如何产生,传播和转导到下游典型生化/转录反应的途径,以及4)向相关领域的许多实验室传播协议和试剂,生物电已经进入了一个新的时代。至关重要的是,该领域因缺乏工具而受到阻碍:变革性影响需要许多实验室能够对体内离子通量和跨膜电压进行严格的时空控制。光遗传学(光敏离子通道的表达)是一个令人兴奋的进步,但从未被应用于可兴奋细胞(神经和肌肉)之外,因为现有的设备不允许灵活控制大面积传递的强烈光线-这是开发或再生系统(器官,整个动物或生物工程构建体)时的必要条件。该项目将开发一个自动化,高度通用的光遗传学研究站,扩展现有技术,使模型系统中的电压梯度实验控制成为可能。该平台围绕计算机控制的显微镜构建,适用于从小动物到单个细胞的任何工作,该平台将允许任何拥有分子生物学和显微镜的实验室在任何情况下对生理学和生物电的作用进行筛选和有针对性的实验。 这将通过改变如何计划、执行和分析功能性体内生理学实验的最新技术水平,对几个基本领域产生重大影响。 Aim 1利用商业伙伴关系和当地工程和光学合作者,建立一个基于光的平台,控制任何所需细胞群的静息电位。目的2通过在体内控制干细胞衍生物和在非洲爪蟾系统中调节器官模式的原理验证应用验证该系统。这个IDBR平台将改变功能电生理学领域,并有助于破解生物电密码,通过,第一次,使得许多实验室能够容易地收集功能生理学数据。在任何感兴趣的细胞/组织中直接控制电压将使得能够定量地理解生物物理(翻译后)参数如何与基因调控网络相互作用以确定模式形成和组织/器官功能。将监管的一个全新的方面,以几个社区将使该领域真正了解生物物理梯度的作用和信息内容。拟议的活动将涉及少数民族博士生和有才华的年轻博士后研究员在高度跨学科技术的发展生物学的前沿,在基础科学和工程行业之间的合作边缘的培训。 自然界的生物电场形成了一种微妙的“支架”,决定着生物结构的生长和形态,引导着基因网络的活动。任何实验室控制活组织内自然生物电场的能力将改变我们理解和控制组织和器官形状的能力。这将对理解复杂身体部位的进化,以及最终推动新的合成生物学和生物工程应用产生重要影响。这项技术的直接受益者不仅是将在最先进的学习模块中使用这种设备的本科生和其他学生,而且整个社会最终将受益于这项技术在生物医学中的应用(体外器官的生物工程,再生套管和由活组织制成的强大计算设备的开发)。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Michael Levin其他文献
Exactly Solvable Model for a Deconfined Quantum Critical Point in 1D.
一维解限量子临界点的精确可解模型。
- DOI:
10.1103/physrevlett.130.026801 - 发表时间:
2022 - 期刊:
- 影响因子:8.6
- 作者:
Carolyn Zhang;Michael Levin - 通讯作者:
Michael Levin
Testing the applicability of idionomic statistics in longitudinal studies: The example of ‘doing what matters’
测试惯用统计在纵向研究中的适用性:“做重要的事情”的例子
- DOI:
10.1016/j.jcbs.2024.100728 - 发表时间:
2024 - 期刊:
- 影响因子:5
- 作者:
Baljinder K. Sahdra;Joseph Ciarrochi;Korena S. Klimczak;Jennifer Krafft;Steven C. Hayes;Michael Levin - 通讯作者:
Michael Levin
Consensus statement CONSENSUS STATEMENT OF THE MANAGEMENT OF SEVERE, DIFFICULT-TO-TREAT ATOPIC DERMATITIS IN ADULTS AND ADOLESCENTS IN SOUTH AFRICA AND THE ROLE OF BIOLOGICS
共识声明 南非成人和青少年严重难治特应性皮炎的治疗及生物制剂作用的共识声明
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
M. Susanna;J. Sarah;Michael Levin;Tshegofatso;Robert;Willem I Visser - 通讯作者:
Willem I Visser
Total IgE in urban Black South African teenagers: The influence of atopy and helminth infection
南非城市黑人青少年的总 IgE:特应性和蠕虫感染的影响
- DOI:
10.1111/j.1399-3038.2007.00663.x - 发表时间:
2008 - 期刊:
- 影响因子:4.4
- 作者:
Michael Levin;P. N. Souëf;C. Motala - 通讯作者:
C. Motala
Particle-hole symmetry and electromagnetic response of a half-filled Landau level
半填充朗道能级的粒子孔对称性和电磁响应
- DOI:
10.1103/physrevb.95.125120 - 发表时间:
2016 - 期刊:
- 影响因子:3.7
- 作者:
Michael Levin;D. Son - 通讯作者:
D. Son
Michael Levin的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Michael Levin', 18)}}的其他基金
Extending Max-Pressure Control for Traffic Network Operations
扩展交通网络运营的最大压力控制
- 批准号:
1935514 - 财政年份:2019
- 资助金额:
$ 69万 - 项目类别:
Standard Grant
CAREER: Bulk and boundary properties of topological matter
职业:拓扑物质的体积和边界特性
- 批准号:
1254741 - 财政年份:2013
- 资助金额:
$ 69万 - 项目类别:
Continuing Grant
Collaborative Research: CDI Type-1: A Computer Framework for Modeling Complex Pattern Formation
合作研究:CDI Type-1:复杂模式形成建模的计算机框架
- 批准号:
1124651 - 财政年份:2011
- 资助金额:
$ 69万 - 项目类别:
Standard Grant
A Device for Automated Large-Scale Morphological and Behavioral Screening
一种用于自动化大规模形态和行为筛查的设备
- 批准号:
0352370 - 财政年份:2004
- 资助金额:
$ 69万 - 项目类别:
Standard Grant
CAREER: Biophysics of Flatworm Regeneration
职业:扁虫再生的生物物理学
- 批准号:
0347295 - 财政年份:2004
- 资助金额:
$ 69万 - 项目类别:
Continuing Grant
Morphogenetic Role of Serotonin in Very Early Embryogenesis
血清素在早期胚胎发生中的形态发生作用
- 批准号:
0234388 - 财政年份:2003
- 资助金额:
$ 69万 - 项目类别:
Standard Grant
相似海外基金
Robotic workstation to enable multiplexing for single-cell proteomics
机器人工作站可实现单细胞蛋白质组学的多重分析
- 批准号:
BB/X019160/1 - 财政年份:2023
- 资助金额:
$ 69万 - 项目类别:
Research Grant
An Intelligent Workstation for Robot-Assisted Microsurgery & Tele-Operations
机器人辅助显微外科智能工作站
- 批准号:
477883 - 财政年份:2023
- 资助金额:
$ 69万 - 项目类别:
Operating Grants
Local manufacturing of unique Braille workstation for the creative industries
为创意产业本地制造独特的盲文工作站
- 批准号:
10070066 - 财政年份:2023
- 资助金额:
$ 69万 - 项目类别:
Collaborative R&D
Multiplexed enzyme-linked immunosorbent assay workstation for clinical research
用于临床研究的多重酶联免疫吸附测定工作站
- 批准号:
10413539 - 财政年份:2022
- 资助金额:
$ 69万 - 项目类别:
MRI: Acquisition of Broadband and All-in-One Optical Workstation for Micro-scale Vibration and Topography Measurement
MRI:购置宽带一体式光学工作站,用于微尺度振动和形貌测量
- 批准号:
2216310 - 财政年份:2022
- 资助金额:
$ 69万 - 项目类别:
Standard Grant
Impact of workstation and wearable technologies on musculoskeletal disorder risk in computer-intensive sedentary environments
工作站和可穿戴技术对计算机密集型久坐环境中肌肉骨骼疾病风险的影响
- 批准号:
RGPIN-2020-05591 - 财政年份:2022
- 资助金额:
$ 69万 - 项目类别:
Discovery Grants Program - Individual
Purchase of an Echo 650 acoustic liquid handler with Access workstation
购买带有 Access 工作站的 Echo 650 声学液体处理机
- 批准号:
10176267 - 财政年份:2021
- 资助金额:
$ 69万 - 项目类别:
Reading workstation for clinical contrast echocardiography
临床造影超声心动图读取工作站
- 批准号:
10155647 - 财政年份:2021
- 资助金额:
$ 69万 - 项目类别:
An integrated materials nanofabrication workstation to stack membranes for the Quantum Materials and Device Foundry
集成材料纳米加工工作站,用于为量子材料和器件铸造厂堆叠薄膜
- 批准号:
RTI-2022-00121 - 财政年份:2021
- 资助金额:
$ 69万 - 项目类别:
Research Tools and Instruments
Reading workstation for clinical contrast echocardiography
临床造影超声心动图读取工作站
- 批准号:
10547365 - 财政年份:2021
- 资助金额:
$ 69万 - 项目类别: