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整合代表了科学和技术的巨大挑战之一，现在已广泛接受的是，纳米技术和工程的结合通过实时预测，预防性，预防性，现实保健保健提供了基因组信息的全部潜力，将导致下一项技术革命。 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.该提案是基于临床和社会需求，以快速检测特定的心脏病感染以筛查，诊断和流行病学用途，并涉及涵盖技术的组合；比较基因组学，新型的生物信息学，验证性蛋白质组学，分子工程肽适时配体和微电力力学（MEMS）传感器技术在纳米规模上有效利用纳米规模：设计，制造，功能化和分子patterning。序列是该提议的核心。该技术将用于表征在细菌细胞表面（SAPS）处显示的蛋白质。一旦确定并表征了推定的SAPS，将分析表面蛋白质组的组成，以鉴定靶向生物群的共有蛋白。如果手动执行通常需要数周的时间，而我们的方法需要不到一天才能建立工作流并处理数据。一旦确定了靶蛋白，将使用蛋白质组学和转录组学的组合来确定临床样品中靶基因的表达。然后，这些发展将与分子工程结合使用，以产生一系列定制的工程生物分子，肽适合素，这将识别SAP蛋白。商业合作者Aptuscan将制备小型，稳健的肽序列的肽适体。然后，使用我们专利的光刻3维图案技术将所选的适体与纳米分辨率集成到固态MEMS微型系统中，这些系统将通过我们的Patents Sensor和Molecular Plotening Technologies to Syoltane Morvelsory多样化，将其设计和开发，以在单个传感器表面上整合单个传感器表面上的多种分析能力。最后，该技术将通过与纽卡斯尔卫生保护局区域实验室主任约翰·麦吉（John Magee）合作以及纽卡斯尔（Newcastle）在泰恩医院（Tyne Hospitals NHS NHS NHS NHS基金会的纽卡斯尔的感染预防和控制局主任凯特·古尔德）的合作进行评估。和微尺度水平，用于根据SAP的指纹进行病原微生物的特定检测和鉴定，这些指纹将提供特定生物体的独特识别符基序。这些设备将构成对感染诊断，进度和流行病学的前线监测的宝贵辅助。这有可能通过改善患者护理和管理为NHS提供深远的经济和人类优势。

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)