Unlocking the Secrets of Time: A New Method for Tracking Cellular Changes in the Body

Tuesday - January 30 2024, 18:02 UTC - 9 months ago

Researchers have developed a new technology called Zman-seq, which allows for tracking and measuring changes over time in single cells inside the body. This has revolutionized our understanding of the molecular and cellular changes that occur in diseases and sheds light on their sequence of events. By using a reversible chemical reaction between fluorescent small molecules and proteins found on cells, this technology can label up to four weeks of immune cell dynamics and has been validated in mouse models of diseases. Zman-seq will pave the way for future discoveries and advancements in the study of diseases.

"Time is an illusion." This famous quote by Albert Einstein has sparked countless debates among physicists for decades. But for biologists, there is no question about the importance of time in understanding life as a dynamic system. In fact, recent advancements in technology have allowed biologists to dive deeper into the intricacies of biological systems, uncovering the cellular networks responsible for diseases. However, these investigations have only provided snapshots of what happens inside our bodies, without considering the dimension of time. That is, until now. In a groundbreaking new study, researchers from the Weizmann Institute of Science have developed a method for tracking and measuring changes over time in single cells inside the body. This new technology, called Zman-seq, will revolutionize how we understand the molecular and cellular changes that occur within our tissues and shed light on the sequence of events that lead to diseases.

The concept for Zman-seq came from Dr. Daniel Kirschenbaum, a postdoctoral researcher from Prof. Ido Amit's lab. Kirschenbaum's research focused on glioblastoma, the most common and aggressive brain tumor. He explains, "We usually think of cancer as cells growing out of control, but in reality, it is also the loss of the body's ability, particularly the immune system, to control this growth. And when you look at tumors, a large portion of them are made up of dysfunctional immune cells, sometimes making up one-third or even half of all the cells in a tumor." .

Glioblastoma is a highly immune-suppressive type of tumor, making it difficult to treat. Kirschenbaum's previous research aimed to understand how the immune system fails to stop the growth of these tumors. In Amit's lab, he continued this work and together they made a significant scientific and technological breakthrough with Zman-seq. He explains, "Our goal was to develop a robust, flexible, scalable, and affordable way to label cells with different fluorophores, which are molecules that can absorb and emit light, sequentially over a long period of time." .

Their technology is based on a reversible chemical reaction between these fluorescent small molecules and proteins found on the cells of interest. As time passes, the activity of these proteins is tracked under a microscope, becoming brighter and allowing researchers to distinguish them from younger cells. Kirschenbaum compares it to invisible ink, slowly getting darker over time and allowing them to go backwards and determine when the cells emitted the signal. Their technology can label up to four weeks of immune cell dynamics and has been validated on twenty-five proteins present on all immune cells. In mouse models of autoimmune encephalomyelitis (a widely used experimental model of multiple sclerosis) and glioblastoma, the researchers were able to use Zman-seq to explore the behavior of these cells in real-time, providing a deeper understanding of how these diseases develop and progress.

Single-cell technologies, the tools that allow us to understand what happens inside individual cells, have significantly advanced in recent years thanks to the vibrant single-cell research community. These tools have enabled high-resolution images of diseases and the body's response to medications, identifying rare cell populations, and deciphering cell interactions in tissues. However, without taking into account the dimension of time, these insights are equivalent to getting still-frame images from a movie without understanding the plot. Amit states, "Knowing what happened before and after is not enough to deduce causality, and without this knowledge, we have no chance of understanding the cause and effect relationships." .

With Zman-seq, biologists now have a powerful tool to analyze cellular and molecular data over time and understand the dynamic nature of life in a new way. This groundbreaking technology will pave the way for future discoveries and advancements in our understanding of diseases and their treatment.