The International Regulome Consortium
The International Regulome Consortium (IRC) is a Canadian-initiated research program involving 38 research institutes in 12 countries. The Consortium is definitively mapping the genetic pathways and control systems that govern all cellular and biological functions.
Our Bodies are complex communities of specialized cells, and each cell comes with a similarly complex set of rules governing its function. But how is this diversity generated in normal development, and how is the body able to replace and repair specific cell types lost through injury or disease? The rules that guide cell differentiation are encoded by the genome. The genes that can be expressed in a given cell type are limited by the cellular memory that has been created in previous generations – the cell’s epigenome. Together, the genome and the epigenome prescribe the instructions that guide the cell as it undergoes successive rounds of cellular specialization. Understanding what controls the interaction between the genome and the epigenome, and how the fate of each cell type is regulated requires mapping of this genetic control network.
The Vision
The IRC’s goal is to define the “circuit board” that regulates genes. By understanding how gene expression is regulated, researchers and clinicians will be able to modify the behavior and function of cells. This knowledge will promote new treatments for cancer, Parkinson’s, diabetes and many other diseases.
The International Regulome Consortium (IRC) is building upon the work of the Human Genome Project, which in 2001 produced a detailed description of the genes in the human body.
There are more than 25,000 different genes and about 10,000 are expressed in each of the over 200 cell types in the human body. Genes control growth, development and health - and when problems arise, the result can be diseases such as cancer, Parkinson’s and diabetes. While other research initiatives are cataloguing the proteins that genes manufacture, IRC will map the circuit board that regulates how cells activate genes to produce the proteins the body requires - when they’re needed and in the correct quantities. The body uses about 2,000 proteins called transcription factors (TFs) to regulate gene expression. This expression depends both on the TFs ability to bind DNA, as well as on its ability to recruit other proteins to specific regions of DNA as part of a transcriptional complex. TF complexes and sites of DNA binding are different in every cell type. The IRC is determining how these complexes change throughout cellular differentiation and how DNA binding is affected. Ultimately, the research will lead to an understanding of how proteins are expressed and what determines cell development. By understanding interactions in healthy cells, the IRC will support the biomedical research community in identifying anomalies in cells that are diseased. New treatments will be developed to correct abnormalities using the body’s own genetic instructions. The IRC will also develop computational models that describe the hierarchal regulation of gene expression in representative cell types, including embryonic and adult stem cells. As we move forward, we are extending our work to include human embryonic stem cells (hESC) and induced pluripotent stem (iPS) cells.
“The work of the International Regulome Consortium is revolutionizing our understanding of how cells function at the gene level. Mapping the ‘genetic circuit board’ is allowing us to learn how to manipulate cell development and function. We believe this knowledge will have an immense impact on the development of new therapies, including stem cell therapeutics and new treatments for cancer, Alzheimer’s, diabetes, heart disease and many other diseases.”
Dr. Michael Rudnicki, IRC CEO and Scientific Director
