The 4D Nucleome: Functional Nuclear Organisation in Space and Time

Although it is now well established that the cell nucleus is a highly organized organelle, the implications of nuclear architecture on nuclear functions and vice versa are not well understood. Under the new term “4D nucleome” we understand the whole range of dynamic, biophysical and biochemical properties of chromatin. This includes the structure-function interactions of chromatin domains, regulatory sequences and genes with each other in cis and trans, as well as all their genetic and epigenetic interactions with functional machineries and nuclear bodies.

Exploring the differences among nuclear phenotypes in normal and pathologically altered cell types will shed light on understanding disease as well as the nuclear topography of basic nuclear functions. Such functions include the regulation of transcription, co-transcriptional splicing, DNA replication and repair, as well as import and export functions. These functions depend on the complex interplay of regulatory elements and can be strongly affected by mutations as well as epigenetic changes. Efforts towards an understanding of the 4D nucleome will provide a new framework for understanding the complexity of multicellular organisms, including humans, and will help to further explore the mechanisms of how disturbances of the physiological equilibrium can result in disease.

From the list of open biomedical questions in this area, these are a few that will be addressed during the workshop:

  • Which different types of epigenetic modification exist in the 4D nucleome?
  • When, where, to what extent and over which time scales do modifications occur and what causes them?
  • How do local epigenetic modifications of chromatin and global changes of nuclear architecture interact?
  • How do epigenetic modifications shape key processes such as development and the function of different cell types?
  • Which epigenetic changes and nuclear phenotypes can be induced by environmental stimuli?
  • Which features are observed in certain organisms or cell types but not in others?
  • Which features may have evolved in prokaryotes prior to the evolution of eukaryotes?

 

The major methodological topics to be addressed by the workshop include:

  • Advanced microscopy techniques
  • Specimen preparation and labelling methods
  • High-throughput biochemical approaches
  • Quantitative image analysis and modelling

 

This workshop is intended to bring together specialists from different fields (advanced microscopy, biochemistry, biophysics, molecular biology & epigenetics, informatics etc.) to discuss opportunities for future collaboration.

For further information about this workshop, please see the event’s external website here: www.lanctotlab.org/workshop/.