Detecting infectious organisms: A concerted approach using genomics, molecular engineering and nano-enabled bio-MEMS technologies (AptaMEMS-ID)

检测传染性生物体：使用基因组学、分子工程和纳米生物 MEMS 技术的协调方法 (AptaMEMS-ID)

基本信息

批准号：
EP/G061394/1
负责人：
Calum McNeil
金额：
$ 238.7万
依托单位：
Newcastle University
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2009
资助国家：
英国
起止时间：
2009 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FG061394%2F1
关键词：
Detecting infectious organisms concerted approach

项目摘要

The functional integration of man-made devices and biological systems represents one of the grand challenges of science and technology and it is now widely accepted that a combination of nanotechnology and engineering that harnesses the full potential of genomic information through real-time predictive, preventive, point-of-care healthcare provision will lead to the next technological revolution. However, major progress in the field is unlikely without guidance from the user community combined with interdisciplinary input from molecular genetics and bioinformatics.This project, which lies at the heart of the confluence of nano-, bio-, micro- and genomic technologies, proposes to use nano-enabled biological sensor technology for the development of a point-of-care system for the rapid detection of infectious organisms. The proposal is based around the clinical and societal need for rapid detection of specific nosocomal infections for screening, diagnostic and epidemiological uses and involves a combination of technologies encompassing; comparative genomics, novel bioinformatics, confirmatory proteomics, molecular engineered peptide aptamer ligands and microelectromechanical (MEMS) sensor technologies which exploit effectively at the nano-scale: design, manufacture, functionalization and molecular patterning.The ability of Newcastle University researchers to use e-Science Grid-based workflows to exploit data from microbial genome sequences is at the heart of this proposal. This technology will be used for the characterisation of proteins displayed at bacterial cell surfaces (SAPs). Once putative SAPs are identified and characterised, the composition of the surface proteome will be analysed to identify proteins that are common to target groups of organisms. If performed manually this would normally take many weeks whereas our approach takes less than a day to establish the workflows and to process the data. Once target proteins have been identified, a combination of proteomics and transcriptomics will be used to determine the expression of the target genes in clinical samples.These developments will then be combined with molecular engineering to produce a range of bespoke engineered biomolecules, peptide aptamers, which will recognize specifically the SAP proteins. Peptide aptamers, which are small, robust peptide sequences designed to act as protein recognition modules, will be prepared by the commercial collaborator Aptuscan. The selected aptamers will then be integrated with nanometre resolution, using our patented photolithographic 3-dimensional patterning technique, into solid-state MEMS microsystems which will be designed and developed to incorporate multi-analyte capabilities on a single sensor surface, using a combination of our patented sensor and molecular patterning technologies, to simultaneously detect multiple diverse harmful microorganisms. Finally, the technology will be assessed in healthcare demand-driven application areas by collaboration with Dr John Magee, Director of the Health Protection Agency regional laboratory in Newcastle and Professor Kate Gould, Director of Infection Prevention and Control at the Newcastle upon Tyne Hospitals NHS Foundation Trust.The innovations encompassed in this programme of research will allow the development of a suite of rapid, quantitative sensor systems engineered at the molecular, nano- and micro-scale levels for the specific detection and identification of pathogenic microorganisms on the basis of the fingerprint of SAPs which will provide organism-specific unique identifier motifs. These devices will constitute valuable aids to front line monitoring of infection diagnosis, progress and epidemiology. This has the potential to provide profound economic and human advantages for the NHS through improved patient care and management.

人造设备和生物系统的功能集成是科学技术面临的重大挑战之一，现在人们普遍认为，纳米技术和工程的结合可以通过实时预测、预防、护理点医疗保健服务将引发下一次技术革命。然而，如果没有用户社区的指导以及分子遗传学和生物信息学的跨学科投入，该领域不太可能取得重大进展。该项目是纳米、生物、微米和基因组技术融合的核心，提出使用纳米生物传感器技术开发快速检测传染性生物体的护理点系统。该提案基于临床和社会对快速检测特定医院感染以用于筛查、诊断和流行病学用途的需求，并涉及以下技术的组合：比较基因组学、新型生物信息学、验证性蛋白质组学、分子工程肽适体配体和微机电 (MEMS) 传感器技术，这些技术在纳米尺度上有效利用：设计、制造、功能化和分子图案化。纽卡斯尔大学研究人员使用电子科学的能力利用微生物基因组序列数据的基于网格的工作流程是该提案的核心。该技术将用于表征细菌细胞表面（SAP）上展示的蛋白质。一旦假定的 SAP 被识别和表征，表面蛋白质组的组成将被分析，以识别目标生物体群体常见的蛋白质。如果手动执行，这通常需要数周的时间，而我们的方法只需不到一天的时间即可建立工作流程并处理数据。一旦确定了目标蛋白，将结合蛋白质组学和转录组学来确定临床样本中目标基因的表达。然后将这些进展与分子工程相结合，生产一系列定制的工程生物分子、肽适体，会专门识别 SAP 蛋白。肽适体是一种小而强大的肽序列，旨在充当蛋白质识别模块，将由商业合作者 Aptuscan 制备。然后，使用我们获得专利的光刻 3 维图案化技术，将选定的适体以纳米分辨率集成到固态 MEMS 微系统中，该系统将被设计和开发为在单个传感器表面上结合多种分析物功能，并结合使用我们的专利传感器和分子图案技术，可同时检测多种不同的有害微生物。最后，将与纽卡斯尔健康保护局区域实验室主任 John Magee 博士和泰恩河畔纽卡斯尔医院 NHS 基金会感染预防和控制主任 Kate Gould 教授合作，在医疗保健需求驱动的应用领域对该技术进行评估信任。该研究计划所包含的创新将有助于开发一套在分子、纳米和微米级水平上设计的快速定量传感器系统，用于基于指纹对病原微生物进行特异性检测和识别的SAP 将提供生物体特定的唯一标识符基序。这些设备将为感染诊断、进展和流行病学的一线监测提供宝贵的帮助。通过改善患者护理和管理，这有可能为 NHS 带来深远的经济和人力优势。