The complete sequencing of the human genome has provided an unprecedented opportunity for the study of the structure and function of the human genome. While our genome has historically been viewed as a linear sequence of bases, it has progressively become clear that this is an inadequate way to represent our genetic information. Notably, research over the last 30 years has begun to shed light on the fact that the higher-order, 3-dimensional organization of our genome plays a critical role in the interpretation of the genetic information encoded in our genome. The structure of our genome in the nucleus has been clearly demonstrated to play influential roles in diverse nuclear processes including DNA replication and gene expression. Despite this, our understanding of the structure of our genome within the nucleus remains incomplete. The reasons for this include limitations in the resolution and throughput of existing tools in chromatin topology mapping, a scarcity of the analytical tools for studying genome structure datasets, and the difficulty to relate the nuclear structure to function. Due to recent advancements in molecular methods based on high-throughput DNA sequencing, single cell analytical approaches, and high-resolution microscopy, the time for breaking through these previous limitations has come. We will establish a highly collaborative, innovative team in order to develop the tools necessary to transform our understanding of chromatin architecture and function in mammalian cells. We will begin by developing datasets that establish gold standards for the study of nuclear structure and function using genetic, biochemical and imaging approaches. We will optimize current existing technologies for mapping genome wide chromatin interactions, while also developing novel, complementary approaches for studying chromatin structure. We will also develop innovative analytical methods to interpret the chromatin structural data, unraveling principles of structural- and temporal- chromatin organization. Our highly collaborative team will draw on the diverse experiences of its members to provide a synergistic environment to push the limits of our understanding of nuclear structure. We expect that the tools and datasets generated through the proposed research will dramatically advance our understanding of the chromatin structure and function in human cells.
The proposed research center will bring together a team of investigators with outstanding track records in biology, computation, and physics, to focus on developing transformative tools that will enable the investigation of 3D genome organization in human cells at unprecedented scale, resolution and temporal detail. Results from this study will improve our understanding of the mechanisms of chromatin organization, and facilitate research into the genetic basis of human diseases.
|Annunziatella, Carlo; Chiariello, Andrea M; Esposito, Andrea et al. (2018) Molecular Dynamics simulations of the Strings and Binders Switch model of chromatin. Methods 142:81-88|
|Wang, Yanli; Song, Fan; Zhang, Bo et al. (2018) The 3D Genome Browser: a web-based browser for visualizing 3D genome organization and long-range chromatin interactions. Genome Biol 19:151|
|Esposito, Andrea; Annunziatella, Carlo; Bianco, Simona et al. (2018) Models of polymer physics for the architecture of the cell nucleus. Wiley Interdiscip Rev Syst Biol Med :e1444|
|Sun, Zhe; Wang, Ting; Deng, Ke et al. (2018) DIMM-SC: a Dirichlet mixture model for clustering droplet-based single cell transcriptomic data. Bioinformatics 34:139-146|
|Babiuch, Amy S; Khan, Mehnaz; Hu, Ming et al. (2018) Comparison of OCT Angiography Review Strategies to Identify Vascular Abnormalities in the AVATAR Study. Ophthalmol Retina 2:606-612|
|Yan, Jian; Chen, Shi-An A; Local, Andrea et al. (2018) Histone H3 lysine 4 monomethylation modulates long-range chromatin interactions at enhancers. Cell Res 28:204-220|
|Zhu, Yina; Gong, Ke; Denholtz, Matthew et al. (2017) Comprehensive characterization of neutrophil genome topology. Genes Dev 31:141-153|
|Yu, Miao; Ren, Bing (2017) The Three-Dimensional Organization of Mammalian Genomes. Annu Rev Cell Dev Biol 33:265-289|
|Xiong, Xiong; Zhang, Yanxiao; Yan, Jian et al. (2017) A Scalable Epitope Tagging Approach for High Throughput ChIP-Seq Analysis. ACS Synth Biol 6:1034-1042|
|Hui, Daniel; Fang, Zhou; Lin, Jerome et al. (2017) LAIT: a local ancestry inference toolkit. BMC Genet 18:83|
Showing the most recent 10 out of 23 publications