Yanyu Zhu, Ashwin Balaji, and the Qi lab at Stanford University have recently made a transformative advance. To do this, they created an innovative imaging technology that enabled scientists to witness changes in genomes as they occurred. That was the news, published by the journal Cell on April 15, about a new innovative tool. This new technology holds promise for transforming gene regulation studies in normal cells and in diseases such as cancer.
The human genome is more like a knotted-up ball of yarn. It holds a stunning 3 billion molecular units all arranged in an exact order. Of these, only roughly 2% of these functional units have an influence on gene expression. This process in turn activates important genes to produce proteins that help health and development. The actual three-dimensional architecture of this genomic “string” is hugely influential on which genes are expressed and when. A breakdown in this metabolic machinery can set off a cascade that leads to a variety of diseases. This underscores the crucial importance of knowing what’s going on with genomes.
A New Perspective on DNA Functionality
This evolving imaging tool is a game changer for scientists. Friedland’s model completely upends their view of those noncoding regions of DNA, once written off as unimportant “junk DNA.” Zhu is excited by the enthusiasm surrounding the visualization of various DNA locations. That breakthrough happens not in the engineered cells but on primary cells such as neurons and immune cells.
“When we can see different sites of DNA in primary cells, like neurons and immune cells, that makes me very excited because it hasn’t been seen before,” – Yanyu Zhu.
Qi emphasizes the significance of this study. He is convinced that knowing what all the functions of the other 98% of DNA previously thought to be junk is really important.
“We are trying to learn the secret behind the 98% ‘junk’ DNA,” – Qi.
We hope this research will result in fundamental new understanding of mechanisms of gene regulation and their role in health and disease including precision management of disease.
“No one calls it junk anymore because we know it is very important, but we still lack so much information about what it does, and most importantly, how it plays a role in disease,” – Qi.
The display of chromatin DNA communication is enabled by this cutting-edge imaging tool employing Oligo-LiveFISH technology for dynamic imaging. By using super-resolution microscopy techniques, it detects light from single molecules, allowing for unprecedented visual clarity in observing genetic interactions. The Moerner lab led the development of some of the very first techniques to detect the light emitted by single fluorescent molecules. They were the lifeblood of this effort.
The Technology Behind the Tool
W. E. Moerner, who received the Nobel Prize in Chemistry in 2014 for his contributions to this field, describes the innovation:
This sophisticated new technique provides scientists a window into nanoscale interactions between different DNA locations during the process of gene expression. It provides a more profound understanding of how genes operate under their three-dimensional scenery.
“There are actually a lot of amazing things that can be done with light. What we did was add a special optical component that re-scrambles one spot of light into two spots, so that depth information is encoded in the angle between the two spots,” – Moerner.
The impacts of this exciting new imaging tool go well beyond basic science. By giving scientists a window into gene expression processes in real time, visualization becomes an exciting new avenue. This improves our understanding of many diseases, cancer among them. Balaji highlights the significance of these observations within biological research:
Implications for Gene Expression Research
The collaboration among the Qi lab, Moerner lab, and Andrew Spakowitz’s lab reflects a concerted effort to push the boundaries of genomic research. By elucidating the gene regulatory machinery, we will better understand how genes are turned on and off under varying conditions. This understanding will give us a new perspective on how cells act and react, in health, as well as in disease.
“Transcription itself is fundamental to biology, and we’ve got this nanoscale insight in a way that not many get the chance to see,” – Ashwin Balaji.
As scientists continue to explore the complexities of the genome with this innovative tool, new discoveries may emerge that could reshape current understanding of genetics and its role in human health.
As scientists continue to explore the complexities of the genome with this innovative tool, new discoveries may emerge that could reshape current understanding of genetics and its role in human health.