What is your goal?

Our bodies are constantly fighting against foreign substances. Foreign substances include viruses and bacteria entering from outside to do harm to our body, or cancer cells which have developed inside our body. We have a protection system called “immunity” in our body to fight these foreign substances. “Receptors,” present on the surface of the cells controlling immunity, are at the forefront of this system (Figure 1). These receptors are made of proteins, the size of which is at an invisible level. For example, they are approximately 1 millionth of 1 mm in size. Thanks to these tiny receptor proteins, we are usually able to live without being affected by diseases. However, when the immune system loses the fight happening in this small space, diseases (infections such as colds and flus as well as various cancers) develop. At the same time, if the immune system is too strong, it leads to autoimmune diseases such as rheumatism. If we are able to observe these tiny proteins actually functioning and control their function, the possibility of preventing and curing diseases is anticipated. The idea of recent high-profile biologics is to insert these proteins into our body, thereby curing diseases. In order to do so, it is important to create a large amount of proteins, which are the biologics.

At the same time, proteins also exist on the surface of viruses and cancer cells that do harm to our body. For example, viral surface proteins take in viruses and work hard not to be caught by our immune system.

Figure 1. Immune cells and surface receptor proteins

Image 1. Protein creation using Escherichia coli (upper left), human cultured cells (upper right), and silkworms (bottom)

 

If their function can be stopped, this will also assist in preventing and curing these diseases. Thus, we "create" a lot of proteins and "observe the shape" of proteins in order to understand their actual function. By observing the shape, we add ingenuity to proteins as a drug or design molecules that control the function of proteins.

What kind of experiments are you conducting?

The general method of creating protein involves the use of Escherichia coli. In addition, we have established unique methods using silkworms and human cultured cells, to create proteins that are able to control immunity and infections (Image 1). Basically, proteins are created by incorporating genes, the blueprint of proteins, into cells, collecting the target proteins using the equipment shown in Image 2. With the development of gene engineering, blueprints can be freely rewritten, which enables the designing of better proteins suitable as drugs. This type of research is referred to as protein engineering.

It is impossible to view proteins that are only 1 millionth of 1 mm in size with normal microscopes. Therefore, it is necessary to create protein crystals and analyze them using X-rays (referred to as X-ray crystallography). Please refer to the website for details, but for example, crystals and the shape thereof (3D-conformation) for the surface proteins of measles are shown in Image 3. Some of the reasons why the measles vaccine is effective were revealed from the shape, leading to the possibility of further development of drugs.

Image 2. Protein refining equipment	Image 3. Crystals of the surface protein of measles (left: standard size 10 mm = 0.01 mm) and the 3D-conformation thereof (right)

 

What is your final goal?

The term protein encompasses a wide range of types (it is generally said that over 20,000 types exists in humans, but the actual number is believed to be far greater). I hope to create proteins that can assist in curing the autoimmune diseases such as rheumatism or infections such as AIDS, or molecules that can control them, together with students through our research.

References

(1) MAENAKA Katsumi. "Chapter 15. Biophysiography of the Immune System." Co-editor of "Pharmaceutical Immunology." Nankodo (2006)