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)

• 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

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代表了科学和技术的重大挑战之一，现在人们普遍认为，纳米技术和工程的结合，通过实时预测，预防性，即时护理医疗保健提供利用基因组信息的全部潜力，将导致下一次技术革命。然而，如果没有来自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，建议使用纳米生物传感器技术开发一种即时系统，用于快速检测传染性有机体。该提案基于临床和社会对快速检测特定医院感染的需求，以用于筛查、诊断和流行病学用途，并涉及技术组合，包括：比较基因组学、新型生物信息学、确证性蛋白质组学、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、功能化和分子模式化。纽卡斯尔大学的研究人员能够使用基于e-Science Grid的工作流程来利用微生物基因组序列的数据，这是这项提议的核心。该技术将用于表征细菌细胞表面（SAP）展示的蛋白质。一旦确定和表征了推定的SAP，将分析表面蛋白质组的组成，以确定目标生物群体共有的蛋白质。如果手动执行，这通常需要数周时间，而我们的方法只需不到一天的时间来建立工作流程和处理数据。一旦确定了目标蛋白质，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，然后将这些发展与分子工程相结合，以产生一系列定制的工程生物分子，肽适体，它将特异性识别SAP蛋白质。肽适体是设计用作蛋白质识别模块的小而稳健的肽序列，将由商业合作者Aptuscan制备。然后，使用我们的专利光刻三维图案化技术，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分析物功能，使用我们的专利传感器和分子图案化技术，以同时检测多种不同的有害微生物。最后，该技术将在医疗保健需求驱动的应用领域进行评估，由纽卡斯尔卫生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基金会信托基金会感染预防和控制主任Kate Gould教授合作。该研究计划中包含的创新将允许开发一套快速，在分子、纳米和微米尺度上设计的定量传感器系统，用于根据SAP的指纹对病原微生物进行特异性检测和鉴定，SAP将提供生物体特异性的唯一标识符基序。这些设备将构成对感染诊断、进展和流行病学的一线监测的宝贵辅助手段。这有可能通过改善患者护理和管理为NHS提供深刻的经济和人力优势。

项目成果

One-Port Electronic Detection Strategies for Improving Sensitivity in Piezoelectric Resonant Sensor Measurements.

• DOI: 10.3390/s16111781
• 发表时间: 2016-10-25
• 期刊: Sensors (Basel, Switzerland)
• 作者: Hu Z;Hedley J;Keegan N;Spoors J;Gallacher B;McNeil C
• 通讯作者: McNeil C

Ultrasensitive, rapid and inexpensive detection of DNA using paper based lateral flow assay.

• DOI: 10.1038/srep37732
• 发表时间: 2016-11-25
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Jauset-Rubio M;Svobodová M;Mairal T;McNeil C;Keegan N;Saeed A;Abbas MN;El-Shahawi MS;Bashammakh AS;Alyoubi AO;O Sullivan CK
• 通讯作者: O Sullivan CK

Microbase2.0: A Generic Framework for Computationally Intensive Bioinformatics Workflows in the Cloud

• DOI: 10.1515/jib-2012-212
• 发表时间: 2012
• 期刊: Journal of Integrative Bioinformatics
• 影响因子: 1.9
• 作者: Keith Flanagan;S. Nakjang;J. Hallinan;C. Harwood;R. Hirt;M. Pocock;A. Wipat

Detecting Infectious Organisms: An Concerted Approach using Genomics, Molecular Engineering and Nano-enabled bio-MEMS Technologies

检测传染性生物体：使用基因组学、分子工程和纳米生物 MEMS 技术的协同方法

• 作者: Neil Keegan (Author)