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Methodology for Quantitative Analysis of 3-D Nuclear Architecture

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Advances in Nuclear Architecture

Abstract

In the past 20 years cell biologists have studied the cell nucleus extensively, aided by advances in cell imaging technology and microscopy. Consequently, the volume of image data of the cell nucleus – and the compartments it contains – is growing rapidly. The spatial organisation of these nuclear compartments is thought to be fundamentally associated with nuclear function. However, the rules that oversee nuclear architecture remain unclear and controversial. As a result, there is an increasing need to replace qualitative visual assessment of microscope images with quantitative and automated methods. Such tools can substantially reduce manual labour and more importantly remove subjective bias. Quantitative methods can also increase the accuracy, sensitivity and reproducibility of data analysis. In this paper, we describe image processing and analysis methodology for the investigation of nuclear architecture, and the application of these methods to quantitatively explore the promyelocytic leukaemia (PML) nuclear bodies (NBs). PML NBs are linked with numerous nuclear functions including transcription and protein degradation. However, we know very little about the three-dimensional (3-D) architecture of PML NBs in relation to each other or within the general volume of the nucleus. Finally, we emphasise methods for the analysis of replicate images (of a given nuclear compartment across different cell nuclei) in order to aggregate information about nuclear architecture.

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Authors and Affiliations

  1. Department of Mathematics, Imperial College, South Kensington, London, United Kingdom

    Richard A. Russell & Niall M. Adams

  2. NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, United Kingdom

    Richard A. Russell

  3. Department of Mathematics and Statistics, McGill University, Montreal, Canada

    David Stephens

  4. Division of Molecular Biosciences, Imperial College, South Kensington, London, United Kingdom

    Elizabeth Batty, Kirsten Jensen & Paul S. Freemont

Authors
  1. Richard A. Russell
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  2. Niall M. Adams
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  3. David Stephens
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  4. Elizabeth Batty
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  5. Kirsten Jensen
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  6. Paul S. Freemont
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Corresponding author

Correspondence to Paul S. Freemont .

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Editors and Affiliations

  1. Department of Mathematics, Imperial College, Queen's Gate 180, London, SW7 2AZ, United Kingdom

    Niall M. Adams

  2. Div. Molecular Biosciences, Imperial College London, London, SW7 2AZ, United Kingdom

    Paul S. Freemont

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Russell, R.A., Adams, N.M., Stephens, D., Batty, E., Jensen, K., Freemont, P.S. (2011). Methodology for Quantitative Analysis of 3-D Nuclear Architecture. In: Adams, N., Freemont, P. (eds) Advances in Nuclear Architecture. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9899-3_6

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