Design of molecular tools to study protein dynamics in living cells
研究活细胞中蛋白质动力学的分子工具设计
基本信息
- 批准号:RGPIN-2020-06103
- 负责人:
- 金额:$ 2.11万
- 依托单位:
- 依托单位国家:加拿大
- 项目类别:Discovery Grants Program - Individual
- 财政年份:2020
- 资助国家:加拿大
- 起止时间:2020-01-01 至 2021-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Nature of the Research
Research in the Menard lab lies at the interface of chemistry and neurobiology. We seek to answer fundamental questions about how neurons communicate with their neighbouring cells, the astrocytes. This proposal describes the chemical steps we must take to achieve this goal. A long-term goal of our Chemical Biology research program is to create a chemical toolbox to study proteins that will complement the current genetic methods used by biologists. Specifically, we will: (1) design chemical tools to label proteins in live cells, and (2) apply these probes to understand the molecular mechanisms of synapse elimination in the aging brain. Our multidisciplinary research program integrates techniques of synthetic chemistry, molecular and cell biology, cell imaging, and electrophysiology. A central theme to this proposal is to modify natural products that have been evolved by Nature and use them as molecular probes to target specific proteins.
Significance
To better understand the mechanisms of neurodegeneration, scientists need new sets of tools to investigate protein-protein interactions at the molecular level. Having access to chemical means to monitor proteins without genetic modification would greatly accelerate the study of important cellular processes in health and disease. Current genetic methods to study protein dynamics suffer from significant drawbacks, e.g., protein expression or activity is often perturbed, and new vectors must be re-engineered for each organism. Chemists are uniquely positioned to design small molecules that can be applied at the time of experiment. This ensures we observe normal protein activity. The successful implementation of our proposed methods will help unravel fundamental scientific questions at the frontiers of chemistry and biology. Such molecules will also be attractive tools for live cell assays in the pharmaceutical industry.
Expected Outcomes
This research proposal centers on the synthesis of small molecules that will offer novel means to visualize, label, and influence specific proteins in their native environment. Specifically, we expect this research will afford the chemical biology community with new reagents to achieve the traceless labeling of lysines residues in proteins. The broad applicability of the strategy of modifying natural products will demonstrate that new tools can be created from any ligand to study its associated protein in live cells. While we focus herein on cellular communication between neurons and astrocytes, the set of molecular tools we will use to study the calcium cascade will be applicable to any calcium-active tissue, such as heart cells and muscles. Finally, our approach to learn about chemical reactivity under physiological conditions should also lead to fundamental knowledge to help medicinal chemists design new drugs with covalent linkers (an emerging concept that can increase drug effiency several-fold).
研究性质
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 }}
Menard, Frederic其他文献
From In Situ to satellite observations of pelagic Sargassum distribution and aggregation in the Tropical North Atlantic Ocean
- DOI:
10.1371/journal.pone.0222584 - 发表时间:
2019-09-17 - 期刊:
- 影响因子:3.7
- 作者:
Ody, Anouck;Thibaut, Thierry;Menard, Frederic - 通讯作者:
Menard, Frederic
A Practical Synthesis of 6,8-Difluoro-7-hydroxycoumarin Derivatives for Fluorescence Applications
- DOI:
10.1055/s-0035-1561603 - 发表时间:
2016-06-01 - 期刊:
- 影响因子:2.6
- 作者:
Kerkovius, Jeff K.;Menard, Frederic - 通讯作者:
Menard, Frederic
Rhodium-catalyzed asymmetric allylic substitution with boronic acid nucleophiles
- DOI:
10.1021/ol061777l - 发表时间:
2006-09-28 - 期刊:
- 影响因子:5.2
- 作者:
Menard, Frederic;Chapman, Timothy M.;Lautens, Mark - 通讯作者:
Lautens, Mark
Ligand-Controlled Selectivity in the Desymmetrization of meso Cyclopenten-1,4-diols via Rhodium(I)-Catalyzed Addition of Arylboronic Acids
- DOI:
10.1021/jo100391e - 发表时间:
2010-06-18 - 期刊:
- 影响因子:3.6
- 作者:
Menard, Frederic;Perez, David;Lautens, Mark - 通讯作者:
Lautens, Mark
Time series analysis of tuna and swordfish catches and climate variability in the Indian Ocean (1968-2003)
- DOI:
10.1051/alr:2008045 - 发表时间:
2008-07-01 - 期刊:
- 影响因子:1.1
- 作者:
Corbineau, Ana;Rouyer, Tristan;Menard, Frederic - 通讯作者:
Menard, Frederic
Menard, Frederic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('Menard, Frederic', 18)}}的其他基金
Design of molecular tools to study protein dynamics in living cells
研究活细胞中蛋白质动力学的分子工具设计
- 批准号:
RGPIN-2020-06103 - 财政年份:2022
- 资助金额:
$ 2.11万 - 项目类别:
Discovery Grants Program - Individual
Design of molecular tools to study protein dynamics in living cells
研究活细胞中蛋白质动力学的分子工具设计
- 批准号:
RGPIN-2020-06103 - 财政年份:2021
- 资助金额:
$ 2.11万 - 项目类别:
Discovery Grants Program - Individual
New Chemical Strategies for the Modification and Control of Endogenous Proteins in Living Cells
修饰和控制活细胞内源蛋白的新化学策略
- 批准号:
RGPIN-2014-04982 - 财政年份:2019
- 资助金额:
$ 2.11万 - 项目类别:
Discovery Grants Program - Individual
New Chemical Strategies for the Modification and Control of Endogenous Proteins in Living Cells
修饰和控制活细胞内源蛋白的新化学策略
- 批准号:
RGPIN-2014-04982 - 财政年份:2018
- 资助金额:
$ 2.11万 - 项目类别:
Discovery Grants Program - Individual
New Chemical Strategies for the Modification and Control of Endogenous Proteins in Living Cells
修饰和控制活细胞内源蛋白的新化学策略
- 批准号:
RGPIN-2014-04982 - 财政年份:2017
- 资助金额:
$ 2.11万 - 项目类别:
Discovery Grants Program - Individual
New Chemical Strategies for the Modification and Control of Endogenous Proteins in Living Cells
修饰和控制活细胞内源蛋白的新化学策略
- 批准号:
RGPIN-2014-04982 - 财政年份:2016
- 资助金额:
$ 2.11万 - 项目类别:
Discovery Grants Program - Individual
New Chemical Strategies for the Modification and Control of Endogenous Proteins in Living Cells
修饰和控制活细胞内源蛋白的新化学策略
- 批准号:
RGPIN-2014-04982 - 财政年份:2015
- 资助金额:
$ 2.11万 - 项目类别:
Discovery Grants Program - Individual
New Chemical Strategies for the Modification and Control of Endogenous Proteins in Living Cells
修饰和控制活细胞内源蛋白的新化学策略
- 批准号:
RGPIN-2014-04982 - 财政年份:2014
- 资助金额:
$ 2.11万 - 项目类别:
Discovery Grants Program - Individual
Design of a new catalyst for the asymmetric hydroxylation of C-H bonds
一种新型C-H键不对称羟基化催化剂的设计
- 批准号:
388764-2010 - 财政年份:2011
- 资助金额:
$ 2.11万 - 项目类别:
Postdoctoral Fellowships
Design of a new catalyst for the asymmetric hydroxylation of C-H bonds
一种新型C-H键不对称羟基化催化剂的设计
- 批准号:
388764-2010 - 财政年份:2010
- 资助金额:
$ 2.11万 - 项目类别:
Postdoctoral Fellowships
相似国自然基金
配子生成素GGN不同位点突变损伤分子伴侣BIP及HSP90B1功能导致精子形成障碍的发病机理
- 批准号:82371616
- 批准年份:2023
- 资助金额:49.00 万元
- 项目类别:面上项目
MYRF/SLC7A11调控施万细胞铁死亡在三叉神经痛脱髓鞘病变中的作用和分子机制研究
- 批准号:82370981
- 批准年份:2023
- 资助金额:48.00 万元
- 项目类别:面上项目
PET/MR多模态分子影像在阿尔茨海默病炎症机制中的研究
- 批准号:82372073
- 批准年份:2023
- 资助金额:48.00 万元
- 项目类别:面上项目
GREB1突变介导雌激素受体信号通路导致深部浸润型子宫内膜异位症的分子遗传机制研究
- 批准号:82371652
- 批准年份:2023
- 资助金额:45.00 万元
- 项目类别:面上项目
靶向PARylation介导的DNA损伤修复途径在恶性肿瘤治疗中的作用与分子机制研究
- 批准号:82373145
- 批准年份:2023
- 资助金额:49.00 万元
- 项目类别:面上项目
OBSL1功能缺失导致多指(趾)畸形的分子机制及其临床诊断价值
- 批准号:82372328
- 批准年份:2023
- 资助金额:49.00 万元
- 项目类别:面上项目
O6-methyl-dGTP抑制胶质母细胞瘤的作用及分子机制研究
- 批准号:82304565
- 批准年份:2023
- 资助金额:30.00 万元
- 项目类别:青年科学基金项目
Irisin通过整合素调控黄河鲤肌纤维发育的分子机制研究
- 批准号:32303019
- 批准年份:2023
- 资助金额:30.00 万元
- 项目类别:青年科学基金项目
转录因子LEF1低表达抑制HMGB1致子宫腺肌病患者子宫内膜容受性低下的分子机制
- 批准号:82371704
- 批准年份:2023
- 资助金额:49.00 万元
- 项目类别:面上项目
上皮细胞黏着结构半桥粒在热激保护中的作用机制研究
- 批准号:31900545
- 批准年份:2019
- 资助金额:24.0 万元
- 项目类别:青年科学基金项目
相似海外基金
Parametric design software for nanostructured CRISPR payloads
用于纳米结构 CRISPR 有效负载的参数化设计软件
- 批准号:
10602823 - 财政年份:2023
- 资助金额:
$ 2.11万 - 项目类别:
Decode and design T cell induction by a complex gut microbial community
复杂肠道微生物群落解码和设计 T 细胞诱导
- 批准号:
10572613 - 财政年份:2023
- 资助金额:
$ 2.11万 - 项目类别:
EnzyDock-based Multistate and Multiscale Tools for Covalent Drug Design
基于 EnzyDock 的多状态和多尺度共价药物设计工具
- 批准号:
10575904 - 财政年份:2023
- 资助金额:
$ 2.11万 - 项目类别:
BEYOND BURDEN: NEW TOOLS FOR TUBERCULOSIS ANTIBIOTICREGIMEN DESIGN
超越负担:结核病抗生素方案设计的新工具
- 批准号:
10667002 - 财政年份:2023
- 资助金额:
$ 2.11万 - 项目类别:
Enabling Rational Design of Drug Targeting Protein-Protein Interactions with Physics-based Computational Modeling
通过基于物理的计算模型合理设计靶向药物的蛋白质-蛋白质相互作用
- 批准号:
10710974 - 财政年份:2023
- 资助金额:
$ 2.11万 - 项目类别:
Modeling the mucosal glycopeptide mesh for improved disease understanding and mucin-inspired biomaterial design
对粘膜糖肽网进行建模,以提高对疾病的理解和粘蛋白启发的生物材料设计
- 批准号:
10715230 - 财政年份:2023
- 资助金额:
$ 2.11万 - 项目类别:
Tackling Multifaceted Drug Design Problems with Lambda Dynamics Based Technologies
利用基于 Lambda Dynamics 的技术解决多方面的药物设计问题
- 批准号:
10709879 - 财政年份:2022
- 资助金额:
$ 2.11万 - 项目类别:
Solvation directed drug design: from molecular physics to lead optimization
溶剂化导向药物设计:从分子物理学到先导化合物优化
- 批准号:
10330792 - 财政年份:2022
- 资助金额:
$ 2.11万 - 项目类别:
In Silico Drug Design Targeting RNA Repeat Expansions
针对 RNA 重复扩增的计算机药物设计
- 批准号:
10439166 - 财政年份:2022
- 资助金额:
$ 2.11万 - 项目类别: