Superresolution Method Poised to Better Gene Function Understanding – Photonics.com

BARCELONA, Oct. 18, 2022 An interdisciplinary team from the Centre for Genomic Regulation (CRG) and the Institute for Research in Biomedicine (IRB Barcelona) has developed an imaging technique that captures the structure of the human genome to reveal how individual genes fold at the nucleosome level the fundamental units constituting the genomes three-dimensional architecture. The technique integrates superresolution imaging with advanced computational modeling.

According to the researchers, the method allowed them to image the structure of the human genome at unprecedented resolution. They believe the technique could have a long-term impact on scientific discovery.

Scientists used the technology, called Modeling immuno-OligoSTORM (MiOS), to create and virtually navigate 3D models of genes. Since almost every human disease has some basis in genes, the ability to visualize how genes work could lead scientists to a better understanding of how genes affect the health of the human body. The developers of MiOS hypothesized that taking superresolution microscopy and merging it with advanced computational tools could be a way to image genes at the level of detail necessary to study their shape and function, so as to fully understand their function and regulation.

MiOS showed the distribution of nucleosomes within specific genes in superresolution, through the simultaneous visualization of DNA and histones. It integrated this information with restraint-based and coarse-grained modeling approaches. It allowed quantitative modeling of genes with nucleosome resolution and provides information about chromatin accessibility for regulatory factors such as RNA polymerase II.

According to researcher Juan Pablo Arcon, the method provided a picture, or movie, of the 3D shape of genes at resolutions beyond the size of nucleosomes, reaching the scales that are needed to understand in detail the interaction between chromatin and other cell factors.

We show that MiOS provides unprecedented detail by helping researchers virtually navigate inside genes, revealing how they are organized at a completely new scale, researcher Vicky Neguembor said. It is like upgrading from the Hubble Space Telescope to the James Webb, but instead of seeing distant stars well be exploring the farthest reaches inside a human nucleus.

In the future, observations on genetic information obtained through MiOS could be used to catalog variations in the shape of genes that cause disease, for example. MiOS could also be used to test drugs that may be able to treat a disease by changing the shape of an aberrant gene.

The researchers intend to develop MiOS further, adding additional functionality that can, for example, detect how transcription factors (i.e., proteins involved in the process of transcribing DNA into RNA) bind to DNA.

The research was published in Nature: Structural & Molecular Biology (www.doi.org/10.1038/s41594-022-00839-y).

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Superresolution Method Poised to Better Gene Function Understanding - Photonics.com