Exploring the Building Blocks of the Body

Similar to Vikings or other adventurers exploring undiscovered parts of the world, scientists study the body using special tools, to understand all the parts that make up this amazing structure. They can look at the body’s large “building blocks”—organs, like the heart, lungs, and brain that work together to keep us alive and healthy. However, the exploration does not stop there! Scientists can zoom in even further to study deeper levels of building blocks: tissues (Figure 1). Tissues are groups of cells working together to perform the vital functions of organs, like the lung tissues that absorb oxygen when we breathe, or the heart muscle tissue that pumps blood through our bodies.

Going deeper into the mysteries of the body, scientists can investigate cells, the tiny building blocks of tissues. Each cell contains a special guidebook, in the form of genes. The genes are together an “instruction manual”, telling the cells how to behave, what proteins to produce, and which functions to perform. The proteins then carry out many different functions depending on where in the body and in which tissue the cell is located (Figure 1).

Scientists in Sweden are building a huge collection of maps of the body called the Human Protein Atlas [1]. This online atlas is free for everyone to use, ensuring that anyone can join the expedition throughout the amazing human body. Like Vikings sailing unknown seas, researchers use the Atlas as a helpful map to find their way. By locating especially interesting proteins, scientists can discover the answers to important medical questions, like finding out what might be causing problems like cancer [2, 3].

The “Tissue” chapter of the Human Protein Atlas explores 44 different types of normal human tissues, helping scientists to understand the body’s construction [4]. But how do the Atlas creators generate these maps? They use various technologies to create vivid images, charting the locations of specific proteins within our organs and tissues.

Tools to Build the Human Protein Atlas

Scientists use several cool tools to explore the tissues and cells of the human body. Data gathered using some of these tools can be assembled into the “maps” of the Human Protein Atlas.

Gathering Tissues for the Tissue Chapter of the Human Protein Atlas

First, scientists gather real human tissues from hospitals. These tissues come from kind people who agree to help science by donating their tissues to research. Sometimes tissues are collected during surgeries performed when a patient needs treatment or to find out what is wrong. Donors’ personal details are kept secret to respect their privacy; thus, scientists only know a few things about the donors, like their age. Once scientists have the tissues, they keep them safe in a special wax block called a formalin-fixed paraffin-embedded (FFPE) block (Figure 2A). This block helps preserve the tissues for a long time, up to decades, without the proteins breaking down. Scientists can then cut thin slices of the tissue, like cutting a slice of cheese (Figure 2B), put the slices on glass slides (Figure 2C), and look at them under a microscope (Figure 2D).

Now that the tissues have been collected, let us explore how they can be used to create detailed maps of the human body and its organs.

Examining Tissues Using Tissue Microarrays

Instead of studying one tissue at a time, scientists can use a technique called tissue microarrays (TMA) to examine many tissue samples at once [5]. Imagine having many FFPE blocks, each one containing a preserved tissue sample from a different donor. To study many tissues efficiently, scientists punch tiny cores, like small cylinders, from these blocks—similar to how garlic comes out of each small hole in a garlic press. Each core represents a specific tissue or organ. Then, scientists place these cores into an empty wax block, arranging them in an organized grid pattern (Figure 2B). This block, now consisting of multiple tissue samples, is the TMA. Once the block is prepared, scientists can cut thin sections (like slices of cheese), and place them on glass slides for analysis under a microscope (Figure 2D). This approach lets scientists analyze many tissue samples at once, making their exploration more efficient and helping to save precious patient samples for other research projects.

Finding the Location of Proteins With Immunohistochemistry

Next, to see where specific proteins are located in tissue samples, scientists can use a technique called immunohistochemistry (IHC) [5]. IHC uses molecules called antibodies, which act like guided arrows, precisely designed to target and stick to the particular proteins the scientists want to find. All antibodies do not match all proteins—they are designed to each find a specific part of a specific protein, allowing scientists to pick and choose which protein they want to see under the microscope by using an antibody that fits that specific protein. When the antibodies find their protein targets, they stick strongly and leave behind a brown-colored stain (Figure 2C). This staining is crucial because it helps scientists to visualize where the proteins are found in the tissues [2], thus creating detailed maps showing where specific proteins are located in various organs. Moreover, IHC enables scientists to determine whether a protein is specific to a particular organ, tissue, or cell type, or if that protein is present in multiple locations and tissues.

Multiplex Immunofluorescence to see Multiple Proteins at Once

In the quest for a deeper understanding, scientists use methods that go beyond conventional IHC, allowing them to study multiple proteins simultaneously, generating an even more detailed map [3]. With one such technique, called multiplex immunofluorescence (mIF), scientists target several proteins at the same time using multiple antibodies, each with a different fluorescent color (Figure 2C). The fluorescent colors “light up” multiple proteins at the same time within cells and tissues, providing a richer understanding of their locations and functions (Figure 2E). By studying the complex interactions between proteins, scientists can understand how our cells and tissues function and what happens when things do not work properly. For example, cancerous tumors can express different proteins than healthy cells, making it possible for scientists to visualize cancer cells by targeting those specific proteins.

These techniques, all part of the scientist’s toolkit, helped to create the Human Protein Atlas—a guide to understand the body’s architecture, open for everyone to use (Figure 2F).

Exploring the Human Body: A Scientific Viking Voyage!

Let us set sail on an exciting journey, where scientists use their tools to explore the human body. These examples are studies made with the antibodies and techniques used to create the Human Protein Atlas.

Voyage 1: Cilia in the Fallopian Tube

The fallopian tubes connect the ovaries to the uterus in the female reproductive system. If you zoom in on the inside of the fallopian tube, there are special cells with tiny hair-like structures called cilia. Cilia help to move eggs from the ovaries to the uterus by pushing them forward. If a fertilized egg reaches the uterus, it can grow into a baby. Scientists use a viewing tool, like mIF, to study the proteins of the fallopian tube cells to understand how they collaborate to take care of the eggs. Each protein within the ciliated cells has its own color in this technique, allowing scientists to map the various parts of the cells to understand how they work together and thereby understanding the structure of the cells (Figure 3A).

Voyage 2: the Battle Against Ovarian Cancer

The ovaries are another part of the female reproductive system, located at the end of the fallopian tubes. Ovarian cancer is a serious form of cancer in which the cells in the ovary start to divide in an uncontrolled way. The symptoms are vague, making this cancer type hard to detect. Using tools like mIF, scientists can see cancer cells spreading like invaders (Figure 3B), but they can also spot cells of the immune system fighting back to protect the body from the cancer cells!

The Human Protein Atlas—A Way to Go Deeper

In conclusion, exploring the body’s construction at the microscopic level unveils its fascinating architecture. Scientists, acting as explorers, can use the Human Protein Atlas as a guide to decode health and disease mysteries, increasing the understanding of how cells and proteins work. Hopefully, the Human Protein Atlas will continue contributing to significant discoveries and paving the way for a healthier future.

Glossary

Proteins: ↑ Tiny building blocks of life that do many important jobs in our bodies, like helping us grow, stay healthy, and fight sickness.

Formalin-Fixed Paraffin-Embedded (FFPE) Block: ↑ A way to store tissue samples in “wax” and to keep their structure. They can be stored like this for decades.

Tissue Microarrays: ↑ A wax block containing many different samples. This allows for scientists to study many different samples and/or tissues at the same time.

Immunohisto-Chemistry: ↑ A technique scientists use to stain or color proteins using antibodies, allowing them to see the proteins under a special microscope.

Antibodies: ↑ Molecules that stick to specific proteins in tissues, helping scientists to find and study those proteins. Antibodies are a normal part of the immune system that scientists have learned how to use in their experiments.

Multiplex Immunofluore-Scence: ↑ This technique makes it possible to see many different proteins at the same time which allows scientists to get an even deeper understanding of the structure of cells and tissues.

Immune System: ↑ The body’s defense team, protecting us against bad germs and sickness.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.