- Cancer Biology & Biomarkers
- Chromatography & Mass Spectrometry
- Contract Research, Clinical Trials and Outsourcing
- Drug Discovery
- Drug Targets
- Flow Cytometry
- Informatics & Lab Automation
- Ingredients, Excipients and Dosages
- Microbiology & RMMs
- NIR, PAT & QbD
- Raman Spectroscopy
- Screening, Assays & High-Content Analysis
- Thermal Processing
- Events & Workshops
Anthony Davies - Articles and news items
New approaches to cell based assays for high content screening and analysis.
Reduce, reuse, recycle: how drug repositioning is finding its niche in drug discovery.
Workshop Review: Biochemical assays for screening.
Issue 3 2012, Screening / 10 July 2012 / Anthony Mitchell Davies & Anne Marie Byrne, Department of Clinical Medicine Trinity College Dublin; Holger Erfle, BIOQUANT-Zentrum Ruprecht-Karls-Universität Heidelberg; Graham Donnelly, Rita Murray & Peadar MacGabhann, Biocroi Ltd
One of the major limitations of performing large-scale High Content Analysis (HCA) screens is reagent cost, indeed this fact has been a key driver in the development of assay size reduction strategies here at The Irish National Centre for High Content Screening and Analysis at Trinity College’s Department of Medicine.
As well as the obvious financial advantages of reducing assay volumes, we have also identified other key benefits to this approach, namely: Higher throughput; Improved signal to noise; Suited for the use of valuable cells, e.g. primary cells; Reduced storage and research space; Improved mixing of reagents.
The practicalities of performing cell based assays at the nano-litre scale: Despite the clear benefits to adopting miniaturisation, there are several significant barriers that must be overcome before these methods can be utilised. These are sample delivery / handling and environmental stability.
The World Cancer Report (2008) predicts a 50% worldwide increase in cancer incidence by 2030, predicting 75 million people living within a five year diagnosis of cancer1. This increase is partially fuelled by significant medical advances in developed countries ensuring people live longer. However, it is also attributable to developing countries adopting habits linked to cancer risk such as increased uptake of smoking and the acquisition of western diets. In 2007, cancer caused approximately 7.6 million or 13% of all human deaths2. Cancers associated with the greatest mortalities are lung, stomach, colorectal, liver and breast cancer respectively. There are modifiable risk factors common to many malignancies, including tobacco, overweight or obesity, poor physical activity, dietary factors, alcohol, sunlight exposure and chronic infection. Effective prevention will reduce the risk of cancer, and efficient screening will enable many to be successfully treated for their disease.
1. How significantly do you feel the Drug Discovery Process has benefited from the application of High Content Analysis techniques?
Anthony Davies: Since the mid 1990’s High-content analysis (HCA) has primarily been used in the later stages of the pre-clinical drug discovery process. However, as HCA techniques have developed and evolved, so has the role of this technology within the discovery process. Today HCA is integrated earlier in drug discovery, for example this technology is now widely utilised in target validation where contextual information obtained from cell based assays allows for better characterisation of biological mechanisms.
Development of cardiac cell based assays for study of cardiac disease – in with the new by automating the old
Approximately 45% of all deaths and 50% of all hospitalisations in the western world are a direct result of cardiovascular disease. Cardiomyocyte hypertrophy is a mechanism by which myocardial mass is increased to compensate for any elevated physical demands placed upon the heart, thus ensuring that adequate perfusion of body tissues is maintained during these periods. However, if the hypertrophic response persists, the heart enters a critical transition from compensatory to a patho-physiological de-compensatory state which eventually leads to heart failure.
Automated workflow optimisation and assay development strategies for High Content Research Facility, Trinity College Dublin
High Content Screening (HCS) is becoming increasingly utilised as an early drug-discovery and basic research tool for defining the functions of genes, proteins and other biomolecules in normal and abnormal cellular functions. HCS involves the integration of a number of preparation steps which include; cell-sample preparation, fluorescent labelling, image acquisition, image processing, image analysis, information management and knowledge mining.
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