Our genome, our DNA, has taken a central place in our daily life, whether we think about our health, our well-being and longevity, our susceptibility to disease, our aptitude for learning, and our adaptation and responses to diet, drugs and the environment. Yet despite having successfully sequenced the full human genome, it is not enough to make sense of its function as a whole. Developing the technologies to empower the community to address this major issue represents one of the most significant S&T challenge that the biomedical world will have to deal with in the next decade to come.
An exciting emerging view is that the genome offers a lot more than a simple passive library of genetic information. It functions as a powerful information retrieval system that dynamically changes shape and conformation to selectively expose selectively the genetic information (genes) that are required for a particular cell type, while filing away and hiding other information that is not required. To adapt to the diverse aspects of our life such as embryonic development, ageing, response to diet, learning or environmental stress, it is now proposed that distinct changes in the 3D arrangement of our genomes occur. These changes are coordinated through regulation of gene expression. Just as a map of the world is more than a mere list of places and street names, the nucleus cannot be reduced to a string of letters. The orchestrated organization of the genome impact all scales of an organism, from setting diverse cell identities, specific functions, cell cooperation, tissue organization, morphogenesis and eventually the maintenance of an entire body. How the genome functions within the space of the nucleus and its dynamic context has remained an elusive challenge until recently with the advent of new technologies.
As many other emerging areas in science, ours is a technology driven field. The challenge in the 4DNucleome Initiative includes advanced technologies from four interdisciplinary fields at its core: cell biology, molecular genetics, imaging, and computational modelling. Recent technological advances in high resolution and live microscopy, high-throughput genomics/cell biology approaches and modelling, coupled with increased awareness of the importance of genome organization will soon allow to perform precision analysis of our genomic organization and its dynamic translations from one epigenome to another, as cells differentiate, age, and respond to the environment. This a perfect time to launch a concerted effort towards characterizing the dynamic organization of the genome, the epigenome, and the rules that govern determination and maintenance of cell types in face of both internal and external stress linked to disease. We can now envisage having a complete 3D atlas in time (4D) of nuclei within the many cell types that form our body. The huge challenge before us is to take the one dimensional genome sequence provided by the Human Genome Project, decorated with the valuable annotations provided by the ENCODE project, and create an integrated 4D understanding of the complexity of this incredible, living, breathing machine that holds the secret of life.
Download the next PDF for further description of the 4DNucleome Initiative in Europe.