Diagnostics on demand: a biosensor platform for multiplexed small molecule detection
按需诊断:用于多重小分子检测的生物传感器平台
基本信息
- 批准号:10720755
- 负责人:
- 金额:$ 43.6万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-01 至 2027-08-31
- 项目状态:未结题
- 来源:
- 关键词:Abscisic AcidAccelerationAcidsAddressAffinityAntibodiesBasic ScienceBindingBiochemicalBiologicalBiological AssayBiomedical ResearchBiosensorBiotechnologyCarrier ProteinsChemicalsChemistryClinicalConsumptionDepositionDetectionDevelopmentDiagnosticDiagnostic Reagent KitsDiagnostic testsDimerizationDirected Molecular EvolutionEngineeringEnvironmental MonitoringEnzymesFDA approvedGeneticHomeImmobilizationImmunoassayKineticsLegalLibrariesLigandsMediatingMedicalMethodsMutationNatural ProductsPharmaceutical PreparationsPlantsProcessProtein EngineeringProteinsReceptor ActivationResearchSpecific qualifier valueSpeedSubstance of AbuseSurfaceTechnologyTestingTherapeuticTimeWorkWorkplaceanalogchemical synthesisclinical diagnosticscomputational pipelinescostdesigndetection limitdetection platformdrug testingempowermentexperiencehigh throughput screeninghome testimmunogenicimprovedinterestmetermultiplex diagnosticsnew technologynovel diagnosticsparallelizationpoint-of-care diagnosticspublic repositoryreceptorreconstitutionscaffoldsensorsmall moleculetool
项目摘要
Small molecule detection is central in many biological, medical, and legal domains,
including basic research, clinical diagnostics, environmental monitoring, and workplace drug
testing, among other applications. The most widely deployed diagnostics are
immunoassay-based that utilize antibodies raised against ligand-protein conjugates. These
easy-to-use assays enable applications as diverse as point-of-care diagnostics, in-home
testing, and real-time environmental monitoring in the field. Although small molecule
immunoassays are powerful, they are time-consuming and costly to develop because analogs
of target molecules suitable for conjugation to immunogenic carrier proteins must be
chemically synthesized. New methods that enable the routine creation of small molecule
sensors using native molecules would radically increase the speed and decrease the costs
required to develop new diagnostic tests. The proposed work addresses this by building a
technology that will make developing new small molecule biosensors as easy and reliable as
developing new antibodies. We will accomplish this using a versatile new sensing scaffold –
the plant abscisic acid receptor PYR1. This receptor participates in chemical-induced
dimerization with its binding partner, HAB1. We recently described a directed evolution
pipeline for creating PYR1/HAB1 dimerization (PAIR) sensors and have created sensors for
116 small molecules, including Δ9-THC, 20 FDA-approved drugs, and dozens of natural
products. These sensors can be used to create ligand-regulated genetic circuits, drive
ligand-mediated reconstitution of split enzymes, and rapidly create sensitive diagnostic tests.
While our platform is powerful, improvements in hit rate, throughput, and the chemical
space it can access are needed to empower high-efficiency sensor development; to achieve
this, we will combine strain engineering, high-throughput screening, and computational design.
Our improved pipeline will be used for 1-step isolation of >1000 moderate-affinity sensors of
FDA-approved drugs and other medically-relevant small molecules. 100 of these will be
evolved to high-affinity (nM) sensors by subsequent rounds of directed evolution. In parallel,
we will develop methods for converting these sensors into multiplexable diagnostics. The
technology developed will deliver new tools and methods for developing sensors of
user-specified molecules and open the door to user-specified chemical-regulated processes,
will have broad biomedical relevance and will advance biomedical research and clinical and
environmental diagnostics.
小分子检测是许多生物、医学和法律领域的核心,
包括基础研究、临床诊断、环境监测和工作场所药物
测试等应用程序。应用最广泛的诊断是
基于免疫测定,利用针对配体-蛋白质缀合物产生的抗体。这些
易于使用的检测方法可实现多种应用,如现场护理诊断、家庭诊断
测试和现场实时环境监测。虽然分子小
免疫测定很强大,但开发起来既耗时又昂贵,因为类似物
适合与免疫原性载体蛋白缀合的靶分子必须是
化学合成的。能够常规创建小分子的新方法
使用天然分子的传感器将从根本上提高速度并降低成本
需要开发新的诊断测试。拟议的工作通过建立一个
技术将使开发新的小分子生物传感器变得像
开发新的抗体。我们将使用多功能的新型传感支架来实现这一目标 -
植物脱落酸受体 PYR1。该受体参与化学诱导的
与其结合伙伴 HAB1 形成二聚体。我们最近描述了定向进化
用于创建 PYR1/HAB1 二聚 (PAIR) 传感器的管道,并已创建用于
包括 Δ9-THC 在内的 116 种小分子、20 种 FDA 批准的药物以及数十种天然药物
产品。这些传感器可用于创建配体调节的遗传电路、驱动
配体介导的裂解酶重建,并快速创建敏感的诊断测试。
虽然我们的平台功能强大,但命中率、吞吐量和化学物质方面的改进
需要它可以访问的空间来支持高效传感器的开发;达到
为此,我们将结合应变工程、高通量筛选和计算设计。
我们改进的管道将用于对超过 1000 个中等亲和力传感器进行一步隔离
FDA 批准的药物和其他医学相关的小分子。其中 100 个将是
通过后续几轮定向进化进化为高亲和力(nM)传感器。并联,
我们将开发将这些传感器转换为多路诊断的方法。这
所开发的技术将为开发传感器提供新的工具和方法
用户指定的分子并打开用户指定的化学调节过程的大门,
将具有广泛的生物医学相关性,并将推进生物医学研究和临床和
环境诊断。
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 }}
Sean Cutler其他文献
Sean Cutler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('Sean Cutler', 18)}}的其他基金
Rapid and responsive development of "spice" sensors using a novel recognition scaffold
使用新型识别支架快速响应地开发“香料”传感器
- 批准号:
10372178 - 财政年份:2021
- 资助金额:
$ 43.6万 - 项目类别:
Rapid and responsive development of "spice" sensors using a novel recognition scaffold
使用新型识别支架快速响应地开发“香料”传感器
- 批准号:
10196698 - 财政年份:2021
- 资助金额:
$ 43.6万 - 项目类别:
相似海外基金
EXCESS: The role of excess topography and peak ground acceleration on earthquake-preconditioning of landslides
过量:过量地形和峰值地面加速度对滑坡地震预处理的作用
- 批准号:
NE/Y000080/1 - 财政年份:2024
- 资助金额:
$ 43.6万 - 项目类别:
Research Grant
Collaborative Research: FuSe: R3AP: Retunable, Reconfigurable, Racetrack-Memory Acceleration Platform
合作研究:FuSe:R3AP:可重调、可重新配置、赛道内存加速平台
- 批准号:
2328975 - 财政年份:2024
- 资助金额:
$ 43.6万 - 项目类别:
Continuing Grant
SHINE: Origin and Evolution of Compressible Fluctuations in the Solar Wind and Their Role in Solar Wind Heating and Acceleration
SHINE:太阳风可压缩脉动的起源和演化及其在太阳风加热和加速中的作用
- 批准号:
2400967 - 财政年份:2024
- 资助金额:
$ 43.6万 - 项目类别:
Standard Grant
Collaborative Research: FuSe: R3AP: Retunable, Reconfigurable, Racetrack-Memory Acceleration Platform
合作研究:FuSe:R3AP:可重调、可重新配置、赛道内存加速平台
- 批准号:
2328973 - 财政年份:2024
- 资助金额:
$ 43.6万 - 项目类别:
Continuing Grant
Market Entry Acceleration of the Murb Wind Turbine into Remote Telecoms Power
默布风力涡轮机加速进入远程电信电力市场
- 批准号:
10112700 - 财政年份:2024
- 资助金额:
$ 43.6万 - 项目类别:
Collaborative R&D
Collaborative Research: FuSe: R3AP: Retunable, Reconfigurable, Racetrack-Memory Acceleration Platform
合作研究:FuSe:R3AP:可重调、可重新配置、赛道内存加速平台
- 批准号:
2328972 - 财政年份:2024
- 资助金额:
$ 43.6万 - 项目类别:
Continuing Grant
Collaborative Research: FuSe: R3AP: Retunable, Reconfigurable, Racetrack-Memory Acceleration Platform
合作研究:FuSe:R3AP:可重调、可重新配置、赛道内存加速平台
- 批准号:
2328974 - 财政年份:2024
- 资助金额:
$ 43.6万 - 项目类别:
Continuing Grant
Collaborative Research: A new understanding of droplet breakup: hydrodynamic instability under complex acceleration
合作研究:对液滴破碎的新认识:复杂加速下的流体动力学不稳定性
- 批准号:
2332916 - 财政年份:2024
- 资助金额:
$ 43.6万 - 项目类别:
Standard Grant
Collaborative Research: A new understanding of droplet breakup: hydrodynamic instability under complex acceleration
合作研究:对液滴破碎的新认识:复杂加速下的流体动力学不稳定性
- 批准号:
2332917 - 财政年份:2024
- 资助金额:
$ 43.6万 - 项目类别:
Standard Grant
Study of the Particle Acceleration and Transport in PWN through X-ray Spectro-polarimetry and GeV Gamma-ray Observtions
通过 X 射线光谱偏振法和 GeV 伽马射线观测研究 PWN 中的粒子加速和输运
- 批准号:
23H01186 - 财政年份:2023
- 资助金额:
$ 43.6万 - 项目类别:
Grant-in-Aid for Scientific Research (B)