Scientists at the Howard Hughes Medical Institute have created a powerful new tool called Perturb-Multimodal, or Perturb-Multi for short. This innovative method helps researchers explore how genes control the behavior and function of individual cells within complex tissues, like the liver.Every living organism, from tiny animals to humans, depends on thousands of genes working together in a highly organized way. Different cell types in our body perform unique roles because of which genes are active in them, and how these genes influence cell shape and behavior. Understanding these relationships is key to learning how organs function and how diseases develop.

Traditional genetic studies often look at many cells mixed together, which can hide the details of what happens in individual cells. Perturb-Multi changes that by combining two powerful techniques: imaging and RNA sequencing.

What does Perturb-Multi do?

First, the method uses imaging to look directly at cells inside tissues. Scientists can see how cells change shape and structure when specific genes are altered. At the same time, they use RNA sequencing, a process that reads the messages genes send inside the cell, to find out which genes are turned on or off.

What makes Perturb-Multi unique is that it pairs these two types of information together for the same individual cells. This means researchers can link exactly how a gene change affects both the cell’s appearance and its gene activity.

How did the researchers use this method?

The team applied Perturb-Multi to study hundreds of genetic changes in the mouse liver. The liver is a vital organ responsible for many functions including filtering toxins and managing metabolism. It has special zones where liver cells (called hepatocytes) perform different tasks.

The researchers discovered new insights about how genes control the organization of these zones, how cells respond to stress by managing unfolded proteins, and how fat builds up in the liver, a condition known as steatosis, which is related to liver diseases like fatty liver disease.

By mapping the detailed effects of genes on cell behavior in living tissues, Perturb-Multi helps scientists understand complex biological processes that were hard to study before. This knowledge can accelerate research into diseases that affect the liver and other organs, and support the development of new, more precise treatments tailored to the unique biology of patients’ cells.

Furthermore, the detailed data generated from Perturb-Multi can train advanced machine learning models to predict how cells function, which will help push the boundaries of biomedical research even further.

In summary, Perturb-Multi is a groundbreaking platform that combines the best of imaging and RNA sequencing to reveal the hidden genetic controls of tissue function, offering exciting possibilities for future discoveries in health and disease.