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NIH Common Fund Launches Initiative to Study the Nucleome in Four Dimensions

NEW YORK (GenomeWeb) – The National Institutes of Health's Common Fund has launched a new program to investigate how the DNA in the nucleus of a cell is organized and how this organization is involved in gene expression and cellular function, and how disturbances to this order affect development and diseases.

Called the 4D Nucleome, the program will seek to uncover the nuclear organization in space and time, and will support the development of new technologies for studying how DNA is arranged in cells, NIH said today.

NIH unveiled the program as one of three new "emerging technologies" initiatives that the Common Fund will support. These projects will provide strategic investments aimed at capitalizing on new biomedical research fields that can have a "transformative impact" in the coming years.

"Emerging technologies or new discoveries in each of these new program areas provide the opportunity for a [five to] 10-year investment to radically change the scientific landscape, leading to new therapeutic avenues for many diseases and providing new foundational knowledge," NIH Director Francis Collins said in a statement.

NIH said it has flagged the nucleome as a ripe subject for research because of recent advances in knowledge about genomics and epigenomics, and the development of new technologies for studying and manipulating nuclear architecture.

"We know that DNA is not randomly arranged within the nucleus; instead the organization of the nucleus is tightly controlled. However, the functional consequences of this organization are not well understood," NIH said on the Common Fund's website.

NIH wants to support research to understand the principles that govern the 3D architecture of the nucleus, and how that architecture is related to gene expression, how it changes over time, and how dysfunctional alterations in this organization lead to disease.

The 4D Nucleome program includes six initiatives. One effort, the Nuclear Organization and Function Interdisciplinary Consortium, will include multidisciplinary teams that will develop and validate novel approaches and genome-wide mapping technologies to study nuclear organization. The Nucleomics Tools project will stimulate development and validation of chemical and biochemical technologies for measuring 3D interactions between specific genome loci. The Study of Nuclear Bodies and Compartments initiative will support development of tools and strategies for studying the 3D architecture of the nucleus in relationship to the spatial arrangement of nuclear bodies and molecular machinery that regulates gene expression. The Imaging Tools project will seek to develop high-throughput, high-resolution, and high-content imaging approaches to measure changes in the nuclear organization in live single cells.

The initiative also will include an organization hub as a resource for the nucleome research community, and a data coordinating center.

It was not immediately clear how much the Common Fund will invest in these initiatives, and if NIH plans to issue requests for applications related to the program.

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