The researchers captured how genes fold and work with unprecedented resolution

A new imaging technique captures the structure of the human genome at unprecedented resolution, revealing how individual genes fold at the nucleosome level, the building blocks
that make up the three-dimensional structure of the genome.

Developed by researchers at the Center for Genomic Regulation (CRG) and the Institute of Biomedical Research (IRB Barcelona) in Barcelona, the technique combines high-resolution microscopy with advanced computational modeling
.
This is the most comprehensive method
ever created to study the shape of genes.

Researchers can use the new technique to create and virtually navigate three-dimensional models of genes, not only visualizing their structure, but also providing details
about how they move or how flexible they are.
Because almost every human disease has a genetic basis, understanding how they work can give us a deeper understanding of how they affect human health and disease
.

Ultimately, scientists can use this information to predict what happens when something goes wrong with a gene, for example, by classifying
changes in the shape of genes that cause disease.
The technology could also be used to test drugs that alter the shape of abnormal genes and help discover new treatments
for different types of diseases.

This technique is the next development in imaging techniques for graduate objects, which first began with the invention
of the microscope more than 400 years ago.
These have played a vital role in promoting medicine and human health, such as Robert Hooke first using it to describe cells, and later by Ramón y Cajal of Santiago to identify neurons
.
Despite the tremendous advances made by light microscopy, its limitations became apparent as early as 1873, when researchers stipulated that the maximum resolution of light microscopes could not exceed 0.
2 microns
.

This physiological limit was overcome in the 21st century with the invention of ^{the St}.
Super-Resolution Microscopy, a breakthrough that won the Nobel Prize
in Chemistry in 2014.
Using fluorescence, the researchers extended the limits of light microscopy, capturing events at 20 nanometers, a feat that revealed how life works on an unprecedented molecular scale
.

Super-resolution microscopy has changed the course of biomedical research, allowing scientists to track proteins
in a variety of diseases.
It also enables researchers to study molecular events
that regulate gene expression.
Scientists now hope to add more layers of information to the technology
.

The researchers hypothesize that employing a super-resolution microscope and combining it with advanced computational tools could be a way to image genes at the level of detail needed to
study their shape and function.
An interdisciplinary team of scientists shared their expertise to create a new technique
called immune modeling-oligostorm (MiOS).

The two research groups are part of the Ignite Call of the Barcelona Institute of Technology (BIST), a project that aims to promote the exchange of knowledge between different scientific fields and to explore new ways to
solve complex problems.

"Our computational modeling strategy integrates data from DNA sequencing technology and super-resolution microscopy to provide a basic picture (or film) of a gene's 3D shape at a resolution beyond the size of a nucleosome, reaching the scale needed to understand the interactions between chromatin and other cytokines in detail," said Juan Pablo Arcon, PhD, co-first author of the work and a postdoctoral researcher
at IRB Barcelona .

As a proof of concept, the research team used MiOS to provide new insights into the location, shape, and compression of key housekeeping and pluripotency genes, revealing new structures and details
that could not be captured with traditional techniques alone.
The results were published in Nature Structure and Molecular Biology.

"We show that MiOS provides unprecedented detail to help researchers virtually navigate the inside of genes, revealing how they are organized
on an entirely new scale.
" It's like upgrading from the Hubble Space Telescope to James Webb, but we're not going to explore distant stars, but the deepest places inside the human nucleus," said
study co-first author and co-corresponding author Dr.
Vicky Neguembor, a researcher at CRG.

While many genome-based studies have changed the way we diagnose, treat, or prevent disease, the effects of MiOS are more long-term
.
By revealing how genes work at the nanoscale and how they are modulated, the technology will enable new discoveries in science labs, some of which may eventually translate into clinical practice
.

The research team has taken advantage of MiOS
by exploring genes important for human development.
The team will also continue to further develop MiOS, adding additional capabilities, such as the ability to detect how transcription factors (proteins involved in the process of DNA conversion or transcription into RNA) bind
to DNA.