Nuclear Physics

Quantitative Single-Cell Approaches to Nuclear Organization and Gene Expression

  1. D.R. Larson1,2,4,5
  1. 1Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York 10461;
  2. 2Gruss Lipper Biophotonics Center, Albert Einstein College of Medicine, Bronx, New York 10461;
  3. 3Kavli Institute of NanoScience, Department of BioNanoScience, TU Delft, Lorentzweg 1, 2628 CJ Delft, The Netherlands;
  4. 4Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia 20147
  1. Correspondence: robert.singer{at}einstein.yu.edu

Abstract

The internal workings of the nucleus remain a mystery. A list of component parts exists, and in many cases their functional roles are known for events such as transcription, RNA processing, or nuclear export. Some of these components exhibit structural features in the nucleus, regions of concentration or bodies that have given rise to the concept of functional compartmentalization—that there are underlying organizational principles to be described. In contrast, a picture is emerging in which transcription appears to drive the assembly of the functional components required for gene expression, drawing from pools of excess factors. Unifying this seemingly dual nature requires a more rigorous approach, one in which components are tracked in time and space and correlated with onset of specific nuclear functions. In this chapter, we anticipate tools that will address these questions and provide the missing kinetics of nuclear function. These tools are based on analyzing the fluctuations inherent in the weak signals of endogenous nuclear processes and determining values for them. In this way, it will be possible eventually to provide a computational model describing the functional relationships of essential components.

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