In the realm of biological research, visualization of entire bodies at a cellular level has been a long-standing challenge. However, a revolutionary method called WildDISCO, developed by researchers, is set to change this.
What Is It?
WildDISCO uses standard antibodies coupled with fluorescent markers to map the entire body of an animal, providing detailed 3D maps of structures and shedding new light on complex biological systems and diseases. This groundbreaking technique, recently introduced in Nature Biotechnology, has the potential to transform our understanding of intricate processes in health and disease, paving the way for exciting advancements in medical research.
The Method, aka How It Works?
Traditionally, scientists have relied on genetically modified animals or specialized labels to visualize specific structures and cells of interest in the entire body of an animal. However, these approaches are expensive and time-consuming to create, especially concerning body-wide systems such as the nervous system. WildDISCO, on the other hand, makes use of standard antibodies to map whole bodies of mice, enabling the creation of detailed three-dimensional maps of normal and diseased structures in mammalian bodies in an easy-to-use and cost-efficient way.
The workflow of WildDISCO includes the distribution of antibodies coupled with a fluorescence tag in the whole body of a no longer living animal by perfusion of the blood vasculature.
This is followed by optical clearing of the animal and light-sheet fluorescence microscopy. The scientists detect a fluorescence signal where a specific antibody is bound to the structure, molecule, or cell of interest. Advanced computational tools create body-wide maps of all the specific locations where a molecule of interest is present throughout the body.
If all that doesn't sounds like coming from the wildest of sci-fi movies, let me walk you through the mouse scan to really appreciate what degree of "inspection" you can do with this technology.
The Vision Behind WildDISCO
The vision (no pun!) behind WildDISCO is to develop a comprehensive understanding of how the body works and what goes wrong in complex diseases by knowing where each protein is expressed in the body.
A crucial factor for the success of this project was finding a way to uniformly distribute a fairly large antibody homogeneously throughout every cell of an animal. Prof. Ali Ertürk and his team identified a specific compound that enhances cell membrane permeability and facilitates deep and even penetration of standard antibodies without aggregation.
Computer vision is what gives "the sight" to any robotics application; what you can see on a computer screen can be "explained" in a chain of thoughts to an AI that drives actuators. This technology is not revolutionary in the context of medical practice and understanding, but it can also become the way an AGI can process your specific health information.
Mario Esposito
Impact on the Scientific Community
Using WildDISCO, the researchers created detailed maps of cellular structures leading to entire mouse body atlases, focusing on the nervous system, lymphatic vessels, blood vessels, and immune cells. With this approach, they already discovered that the gut microbiome plays a significant role in developing the enteric nervous system. They also mapped tumor-associated lymphoid structures (TLS) in relation to breast cancer spread which will provide insights into how these structures affect the immune response to tumors.
Furthermore, these atlases are not just in use at Helmholtz Munich but significantly impact the scientific community. Therefore, the high-resolution images are available on their website as online atlases. First authors Dr. Hongcheng Mai and Dr. Jie Luo from the Ertürk lab at Helmholtz Munich emphasize the benefits of whole-body atlases:
Our online atlases have already generated data for published papers. Other scientists have obtained critical data from our atlases, saving time, resources and reducing animal use.
Future of WildDISCO: AI Integration
The method can already facilitate modeling of complex biological systems and diseases by, for example, outlining the path of cancer metastasis and whether the designed treatments reach every single cancer micrometastasis.
Currently, the Helmholtz Munich team works on further enhancing WildDISCO's capabilities. The scientists envision that in the future, the technology allows, for instance, the simultaneous use of numerous antibodies to enable the modeling of multiple-complex systems together.
In addition, the high-quality, large-scale imaging data generated by this technology is what is needed to train artificial intelligence (AI) algorithms, which thrive on large data sets.
Now imagine what we can do with these maps when you combine them with the power of deep learning
says Ertürk. The team is committed to harnessing the power of AI to simulate complex biological systems, with the ultimate goal of understanding diseases and developing new treatments more efficiently via computational predictions without the need for further animal experiments.
Conclusion
WildDISCO is a revolutionary method that is set to transform the field of biological research. Providing detailed 3D maps of entire bodies at a cellular level offers unprecedented insights into complex biological systems and diseases. As the method continues to be refined and enhanced, it promises to drive significant advancements in medical research, ultimately leading to a deeper understanding of health and disease.
