Time-based high-content screening

Lead Research Organisation: Cardiff University
Department Name: School of Medicine

Abstract

Microscopy and cellular imaging has hitherto been amenable to small-scale experimental samples. New approaches to cell-based analysis are required to meet the demanding needs of cell-biology, genetics and experimental therapeutics. At the core is the need to convert images into numbers, this is a significant challenge which would greatly enhance the ability of the biologist to effectively interrogate and interpret complex data. To achieve large-scale imaging experiments we need to address critical issues of data bottlenecks. High-throughput screening instrumentation has been available in the commercial sector for the last five years, therefore the objective is to bring these capabilities to academia. Such equipment not only greatly augments research capacity but provides new opportunities taking a systems approach to cell-biology.

Technical Summary

We have identified a need for cell-based analysis to keep pace with other high-through-put orientated applications such as microarray technologies and proteomics. Our overall strategy is to acquire an image screening capacity capable of high-resolution imaging of live cells. The requirement to undertake systematic kinetic imaging assays for functional genomics and cell biology screening in Cardiff is significant. The purpose of the research equipment bid is to directly address critical issues of bottlenecks in data acquisition, handling and analysis which have thus far restricted high-content approaches. Therefore the overall aim is to establish five integrated screening platforms, which include advanced multiplex acquisition modules, data informatics and data mining tools. The proposed equipment bid will not only greatly augment the imaging capabilities within Cardiff University, but also will enhance our understanding of the best practice for use of such instrumentation for academic research and systems biology.

Publications


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Khan IA (2011) Interoperability of time series cytometric data: a cross platform approach for modeling tumor heterogeneity. in Cytometry. Part A : the journal of the International Society for Analytical Cytology
Pretorius A (2015) Cell lineage visualisation in Computer Graphics Forum
Rachel Errington (Author) (2010) Single cell nanoparticle tracking to model cell cycle dynamics and compartmental inheritance. in Cell cycle (Georgetown, Tex.)
Smith PJ (2008) Impact of overexpression of metallothionein-1 on cell cycle progression and zinc toxicity. in American journal of physiology. Cell physiology
 
Description Cell-based assays derived from timelapse microscopy demand unique solutions enabling image acquisition, image encoding and interrogation of spatio-temporal cellular events in a population context. High-resolution imaging of live cells leads to bottlenecks in data handling and data analysis which have thus far restricted though-put for single cell analysis at Cardiff. The overall objective of this research equipment initiative was to address this critical issue of time-based high-content screening at the School of Medicine (SOM), Cardiff University. This research equipment iallowed us to take an integrated approach to meet the current and projected user demands and capacity.



Objective 1: To build capacity for five screening systems at Cardiff BioImaging each with unique specifications. This consists of three core features (i) to transform existing timelapse instruments for screening, (ii) to obtain new spectral imaging capabilities (iii) to obtain a new 5D multi-parameter acquisition instrument incorporating image deconvolution capabilities.



Objective 2: To develop the capacity for high-level integrated image analysis, informatics and data-mining.



Objective 3: To provide universally supported and centrally accessed image and data management systems, providing a comprehensive platform for optimising image work flow including image archiving, retrieval and analysis audit trailing.



Objective 4: To provide scientific training to users in microscopy, advanced cell-based assay development and bioinformatics.



Objective 5: To work in collaboration with our project sponsor to develop high-through-put dynamic cell-based assays.
Exploitation Route Feedback and collaboration with academics has provided the equipment manufacturers and collaboration partner with the information they needed to improve existing products to meet the needs of their customers. In this case Molecular Devices (UK) Ltd has developed new software to allow us to incorporate a spectral imaging camera with our microscope configuration. It also enabled us to link the camera to acquisition software from a different manufacturer to process the data. The new capability has since been incorporated into different products sold by the company. "This link between our software, Metamorph, and the third party software was a new thing for us which, without this JREI in placel, we wouldn't have developed." The screening microscopy equipment has been used and accessed by industry users and collaborators, for validation purposes and for optimising new probes.
Sectors Digital/Communication/Information Technologies (including Software),Manufacturing/ including Industrial Biotechology
URL http://www.bbsrc.ac.uk/web/FILES/Publications/equipment-manufacturers.pdf
 
Description The award of the JREI and its impact has been to enable the advanced screening of new drug, new reagents that will be of direct benefit to the healthcare industry
First Year Of Impact 2004
Sector Healthcare
 
Description CONTROL OF STEM CELL FATE THROUGH THE DEVELOPMENT OF NOVEL, NON-INVASIVE IMAGING TECHNOLOGIES
Amount £1,500,000 (GBP)
Funding ID EP/H045848/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 10/2010 
End 04/2014
 
Description Intracellular Biophotonic Nanoswitches
Amount £1,300,000 (GBP)
Funding ID EP/F040954/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 11/2008 
End 07/2012
 
Description Collaboration 
Organisation Broad Institute
Country United States of America 
Sector Charity/Non Profit 
PI Contribution Collaboration to develop open-source image analysis tools
Start Year 2010
 
Description New partnerships 
Organisation National Institutes of Health (NIH)
Department National Institute of Standards & Technology (NIST)
Country United States of America 
Sector Public 
PI Contribution A new partnership has been founded on this grant with National Institute for Standards and Technology on timelapse microscopy and mathematical modelling
Start Year 2010
 
Description Tracking DNA damage for high-content screening 
Organisation Molecular Devices LLC
Country United States of America 
Sector Private 
PI Contribution This is a continuation of our partnership with Molecular Devices, where we seek novel analysis and informatics approaches to image data
Start Year 2008
 
Title Patent - MICROTRENCH AND TUMOUR PROLIFERATION ASSAY 
Description The equipment secured via the JREI made a major contribution towards the patent development 
IP Reference WO 2009095666 A1 
Protection Patent granted
Year Protection Granted
Licensed No