High throughput cell biology

High Throughput Cell Biology is the combination of cell biology with automation to address questions from the scale of a single cell to the human Genome. It permits questions to be addressed that are otherwise unattainable using conventional methods. It exploits optics, chemistry, biology and image analysis to permit rapid, highly parallel research into how cells function, interact with each other and how pathogens exploit them in disease.

It has also been called "Omics research" - the interface between large scale biology (Genome, proteome, transcriptome), technology and researchers. High throughput cell biology has a definite focus on the cell, and methods accessing the cell such as imaging, gene expression microarrays, genome wide screening.The basic idea is to ake bench methods and do simply a very large number of them without losing their quality.

High Throughput Cell Biology —a definition

High throughput research can be defined as the automation of experiments such that large scale repetition becomes feasible. This is important because many of the questions faced by life science researchers now involve large numbers. For example, the Human Genome contains at least 21'000 genes, all of which can potentially contribute to cell function, or disease. To be able to capture an idea of how these genes interact with one another, which genes are involved in and where they are, methods that encompass from the cell to the genome are of interest.

to be done

Classical High throughput screening robotics are now being tied closer to cell biology, principally using technologies such as High-content screening. High throughput cell biology dictates methods that can take routine cell biology from low scale research to the speed and accuracy that allows the entire genome to be looked at, very quickly.

It has a greater emphasis on function rather than discovery, and will have its most significant impact in exploring biology as we progress toward models of the cell as a system rather than isolated pathways.

High Throughput Cell Biology —what it is good for

High-Throughput Cell Biology- faster and faster cellular research and discovery

* Ritter, R. (2002). "The Oxford Style Manual". Oxford University Press. ISBN 0-19-860564-1

From one to many—what this offers for research

This technology allows a (very) large number of experiments to be performed, dramatically more than were possible. What is this good for?

High-Throughput cell biology and its technology

High-content screening technology is mainly based on automated digital microscopy and flow cytometry, in combination with IT-systems for the analysis and storage of the data.“High-content” or visual biology technology has two purposes, first to acquire spatially or temporally resolved information on an event and second to automatically quantify it. Spatially resolved instruments are typically automated microscopes, and temporal resolution still requires some form of fluorescence measurement in most cases.This means that a lot of HCS instruments are (fluorescence) microscopes that are connected to some form of image analysis package. These take care of all the steps in taking fluorescent images of cells and provide rapid, automated and unbiased assessment of experiments.

Technology providers

The instruments on the market are summarised here High-content screening.Kits for high-content screening of various target proteins (e.g. p53, c-jun and NFkB) have recently become available from commercial suppliers.

Where we are

The technology can be defined as being at the same development point as the first automated DNA sequencers in the early 1990’s. Automated DNA sequencing was a disruptive technology when it became practical and -even if early devices had shortcomings- it enabled genome scale sequencing projects and created the field of bioinformatics. The impact of a similarly disruptive and powerful technology on molecular cell biology and translational research is hard to predict but what is clear is that it will cause a profound change in the way cell biologists research and medicines are discovered.

Timeline of the evolution of the science and technology

Please contribute with dates and key assay and image analysis technologies...

ee also

*Drug discovery
*High-throughput screening
*Drug discovery hit to lead
*Microscopy
*Flow cytometry
High-content screening

References

* Abraham VC, Taylor DL, Haskins JR., High-content screening applied to large-scale cell biology, Trends Biotechnol. 2004 Jan;22(1):15-22. PMID 14690618.
* Bleicher KH, Bohm HJ, Muller K, Alanine AI., Hit and lead generation: beyond high-throughput screening, Nat Rev Drug Discov. 2003 May;2(5):369-78. PMID 12750740.
* Burdine, L., and T. Kodadek. 2004. Target identification in chemical genetics: the (often) missing link. Chem Biol. 11:593-7. PMID 15157870.
* Carpenter AE, Sabatini DM, Systematic genome-wide screens of gene function, Nature Reviews Genetics, 2004, 5(1):11-22. PMID 14708012.
* Edwards BS, Oprea T, Prossnitz ER, Sklar LA., Flow cytometry for high-throughput, high-content screening, Curr Opin Chem Biol. 2004 Aug;8(4):392-8. PMID 15288249.
* Eggert, U.S., and T.J. Mitchison. 2006. Small molecule screening by imaging. Curr Opin Chem Biol. PMID 16682248.
* Giuliano KA, Haskins JR, Taylor DL, Advances in high-content screening for drug discovery, Assay Drug Dev Technol. 2003 Aug;1(4):565-77. PMID 15090253.
* Milligan G., High-content assays for ligand regulation of G-protein-coupled receptors., Drug Discov Today. 2003 Jul 1;8(13):579-85. PMID 12850333.