Curiosity that “protein is interesting” leads to the elimination of cancer!?

Proteins responsible for biological functions

Recently, cancer diagnosis using nematodes (C. elegans) has become a hot topic. It takes advantage of a phenomenon whereby nematodes detect a certain substance that cancer cells produce.

The detection probably involves proteins in the nematodes’ body, but it has not yet been clarified what proteins detect what substances.

In other words, we are now only using the phenomenon caused by nematodes, but if the mechanism is clarified, it will be a great advance for medical treatment and medicine. Structural biology is responsible for elucidating these mechanisms of organisms.

Structural biology is a research field that seeks to elucidate the functions of living organisms at the molecular level.

Specifically, these molecules of organisms refer to proteins and nucleic acids, which are present in all cells and involved in protein biosynthesis.

When it comes to proteins, many people would imagine nutrients which are the source of muscles, bones, and blood. That is true, but proteins are also very important molecules that are the major components of the protoplasm of all cells and involved in all the vital phenomena caused by cells.

In other words, breathing, walking, thinking, and inspiration all come down to the activities of molecules called proteins.

Proteins exist and are working in all organisms, including humans.

For example, coronaviruses make us sick because they attach to certain cells in our bodies and interfere with their function. At that time, coronaviruses generate a protein to attach to the cells of living organisms.

So, as humans, we want to make antibodies (also proteins) that interfere with the action of this protein. The first thing needed is to reveal the three-dimensional conformation of the protein made by a coronavirus.

Proteins are macromolecular compounds formed by linking a large number of 20 kinds of amino acids in a chain shape. The chain shape is complex and has various three-dimensional structures. such as spiral, folded, and spherical shapes.

In fact, if we know the three-dimensional conformation of the protein, we can elucidate the mechanism of its function.

In other words, if we know the three-dimensional conformation of the protein made by a coronavirus, we can make an effective antibody that interferes with its function.

The method that has long been used to analyze the three-dimensional conformation of proteins is X-ray diffraction. It is a method to analyze three-dimensional conformation using diffraction spots formed by X-rays.

Recently, methods have been developed such as electronmicroscopy and nuclear magnetic resonance (NMR), which uses electromagnetic waves, similar to MRI.

New technologies are being developed because it is very important to know the three-dimensional conformation of proteins.

Cancer treatment using a protein that stores iron

Humans have elucidated the three-dimensional conformations of proteins that enable the unique biology of various organisms, including microorganisms, and applied them to technologies that serve to human beings.

For example, the PCR test for the coronavirus, which is now actively conducted, is a method to check if there is coronavirus DNA in a sample taken from a human body.

However, it cannot be detected if the amount of DNA is small. Therefore, if there is at least a single piece of coronavirus DNA, we replicate it and increase it so that it can be detected.

The most effective way is as follows. First, the sample is heated to 90°C. This unwinds the double-helical DNA chain. In other words, one DNA chain becomes two. If an enzyme (also a protein) that replicates the DNA is used in this state, the DNA can be duplicated and multiplied effectively.

However, even the enzymes known to humans do not work at high temperatures, such as 90°C. The study of bacteria that live in hot environments, such as hot springs, has clarified how the enzymes of these bacteria work even at high temperatures. This has been applied in the PCR test.

Modern efficient PCR testing is made possible because the function of bacteria was elucidated at the molecular level.

This kind of research is being conducted by various researchers all over the world. For example, I am also studying a protein that stores iron. This protein, called ferritin, is found in various kinds of animals and produces tiny iron particles of about 7 nanometers.

What I am doing is basic research, but I believe it is applicable to medical treatment.

For example, it is known that cancer cells die when warmed to 42°C. As normal cells can tolerate temperatures of up to 45°C, hyperthermia is considered to be a cancer treatment that takes advantage of this property.

However, for humans, it is dangerous to raise the whole body to 42°C. Therefore, we use the function of ferritin.

The iron made by ferritin in natural does not stick to the magnet. First, we controled synthetic conditions in Vitro to make iron sticks to the magnet. The point is that we make it react to the magnetic field.

Next, the gene is modified to make the ferritin stick to cancer cells.

When a high-frequency magnetic field is applied with ferritin attached to cancer cells, iron particles, which have been modified to respond to the magnetic field, generate heat.

In other words, we can warm only the part where cancer cells are. By controlling the temperature to 42°C, we can effectively kill cancer cells.

What makes protein-based treatments better than others is that proteins, which are originally biological substances, are less likely to be harmful to the body than chemicals.

Also, when the protein is synthesized by human hands, it is possible to do so in a bioreactor in an aqueous solution at room temperature using the functions of living organisms. Therefore, it is environmentally friendly, which is also a great advantage.

Importance of expanding the base through basic research

Readers of this article may wonder if the practical use of hyperthermia using ferritin is imminent.

However, what I mentioned above has been confirmed in a test tube, and there are still many barriers to be cleared before it can be put into practical use. Actually, in terms of difficulty, basic research and applied research are somewhat different.

For example, sometimes research achievements, such as nanomachines, are reported and attract a lot of attention. However, it is obvious to researchers that proteins are nanomachines in the first place.

For instance, sperm have a flagellum, and swim on their own through the body by waving the flagellum. This flagellum is made up of proteins that act as motors and gears to vibrate it. Cilia, which are composed of the same proteins as flagella, are distributed in the brain and trachea.

Even though the functions of proteins as motors and gears have been elucidated, it is still necessary to study how to control them arbitrarily, and it is difficult to achieve results.

In that sense, I think it will be very important for various academic fields, such as physics, biology, medicine, and engineering, to cooperate across the board, as well as cooperation between industry and academia.

In fact, the research on ferritin mentioned earlier had been developed not only for cancer treatment, but also for efficient solar cells and very small memory devices with interested companies, but these were quite difficult to put into practical use.

However, new technologies and innovations emerge from the accumulation of such trials. In this sense, it is very important to broaden the base of basic research.

Nevertheless, in recent years, it is difficult to receive a research grant if you do not show a goal to be achieved. However, basic research is often triggered by researchers’ curiosity.

In fact, my research on ferritin was sparked by my questioning why proteins can make iron and accumulate it. It was not intended to treat cancer or develop solar cells from the beginning.

Even if we get to those achievements as a result, the beginning of research is curiosity.

That is why I think the starting point of research should be free. Actually, I was taught that way when I was a student. I want the students in my laboratory to feel that research is fun above all.

I understand that you may expect the achievements of basic research to be put into practical use as soon as they are reported, but I hope that you take a long-term view.

I am sure that before you know it, you will find that your life and society as a whole have changed because of new technologies.

* The information contained herein is current as of November 2022.
* The contents of articles on Meiji.net are based on the personal ideas and opinions of the author and do not indicate the official opinion of Meiji University.
* I work to achieve SDGs related to the educational and research themes that I am currently engaged in.

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