University of Dundee experts are assisting in a major international effort to reveal the secrets of human cells.
A team from the University’s School of Life Sciences are to contribute to a new $10 million, multi-institution research centre funded by the National Institutes of Health (NIH), the USA’s largest funder of biomedical research, to develop a better understanding of the three-dimensional structure of cell nuclei and how changes in that structure affect cell functions in health and disease. The project will utilise world-leading open source software developed by Dundee’s Professor Jason Swedlow and his Open Microscopy Environment to integrate and share datasets, allowing the global scientific community to benefit from the centre’s work.
Formally called "Multiscale Analyses of 4D Nucleome Structure and Function by Comprehensive Multimodal Data Integration,” the five-year initiative will be led by Carnegie Mellon University and also include researchers from the University of California; the University of Illinois at Urbana-Champaign (UIUC); Harvard Medical School; San Diego Biomedical Research Institute; Brown University; the Allen Institute for Cell Science; and the National Cancer Institute. It is funded through the 4D Nucleome (4DN) program of the NIH's Common Fund, which sponsors research of broad relevance to the NIH's many specialised research institutes.
“We’re excited to work with a great team of US scientists to build an understanding of the human cell nucleus, which is often referred to as the ‘brain’ of the human cell,” said Professor Swedlow. “Our role will be, in collaboration with project leader Dr Jian Ma’s group at Carnegie Mellon University, to integrate and publish 4D Nucleome’s datasets for use by the global scientific community. The work will be based on tools developed by the Open Microscopy Environment, the project I founded and lead here at the University of Dundee. Everything we build in the 4D Nucleome project will be open source, ensuring that the world’s scientists can benefit from this work.”
A growing body of research shows that the cell nucleus is highly compartmentalised, and that this spatial phenomenon relates to cell function. But scientists do not yet understand how a type of structure in the nucleus called nuclear bodies tug and tether with the chromosomes that carry the genetic code, as well as other biomolecules such as RNA and proteins.
Jian Ma, the lead principal investigator of the new centre and an associate professor in Carnegie Mellon University’s Computational Biology Department, said researchers will be developing fundamental knowledge to provide new insights into the role that the three-dimensional organisation of cell nuclei plays in developmental disorders, aging and other cell processes. "The spatial organisation of the chromosomes in the nucleus, especially the dynamic interactions with nuclear bodies, is critical but we don't have a complete picture of it yet," Ma said. "Our plan is to generate multimodal data, such as imaging as well as genomic data, and develop advanced machine learning algorithms and integrative structure models to make sense of it."
The goal is to find causal relationships between the large-scale spatial genome structure and genome function, such as gene transcription and DNA replication.
Other principal investigators for the multidisciplinary centre are Frank Alber of UCLA, Andrew Belmont of UIUC and Chao-ting Wu of Harvard Medical School. Co-investigators include David Gilbert of San Diego Biomedical Research Institute, Nicola Neretti of Brown, and Susanne Rafelski of the Allen Institute for Cell Science. Tom Misteli, NIH Distinguished Investigator at the National Cancer Institute, is also part of the centre.
This work is supported by the NIH under award number 1UM1HG011593.