Living Creature/Medical Care

Hisashi Haga

Exploring the Mysteries of a “Cell”, the Smallest Unit of Life

Hisashi Haga , Professor

Faculty of Advanced Life Science, Graduate School of Life Science

High school : Hokkaido Asahikawa Higashi High School

Academic background : Graduate School of Science, Hokkaido University

Research areas
Cell Biology, Tumor Biology
Research keywords
Cell Biology, Protein, Cell Movement, Cancer Cell Invasion

What is Cell Biology?

What image comes to mind when you think of a cell? It is said that a single person is composed of approximately 60 trillion cells. All living creatures including animals such as dogs, cats, fish, insects, and plants as well as humans are composed of cells. In addition, a single cell can survive and exist on its own. A size of just 10 to 100 microns (one micron is equal to the size of one thousandth of a millimeter) is packed with a life support system as a “living creature.” If the cell is broken down, it becomes a “material” such as protein, gene, or lipid. This means that the smallest unit of life is a cell. The discipline that studies the mechanism and composition of the cell is Cell Biology.
At our laboratory, we grow cells of human, dogs, and mice to study the mechanisms by which cells move and also the mechanisms that make cells come together and take the form of tissue.


Do Cells Move?

Fig. 1
Fluorescently-Stained Image of Bowel Cancer Cells. 
A clump of cells which are cultivated after establishing
cancer cells metastasized to lung.

Yes. A cell can move by itself. For example, cells are known to move either by themselves or as a group toward the place of destination in the stage where fertilized eggs undergo cleavage (cell division in growth) and then, the form of living creature is made. In addition, it is known that when skin is damaged, the cells around the wound move to mend the wound. Immune cells, such as white blood cells and lymphocyte cells, move around our body day and night to protect us from foreign enemies.
On the other hand, the cell movement can threaten an individual life. Cancer is one example. It is known that once cancer develops, cancer cells acquire the ability to move and create new tumors by moving around all over the body (these phenomena are called invasion and metastasis). 80 to 90% of the patient deaths due to cancer are said to be caused by metastasis.


So Far What Has Been Learned?

Figure 2
Fluorescently-Stained Image of epithelial cell sheets.
The cell groups transform autonomously and take
three-dimensional shapes such as intestinal villi.

Ten thousands of kinds of proteins exist in cells. Among them, it is known that the proteins called actin and myosin, which combine into a fibrous form to generate a contractive force, provide the ability for the cells to be physically active.
Our laboratory revealed some of the mechanisms that control that force. We found that the force that cells exert changes depending on whether one or two phosphoric acid(s) is(are) bonded to the protein called the myosin regulatory light chain, which is bonded to myosin. The cells can control the strength of the force to move by regulating the number of phosphoric acids, similar to a person shifting gears in a car.
This force is also very effective when many cells come together to form a group. Many roles are shared in the group among the cells, such as those cells that exert power, those that don’t exert power, and those which determine the direction of movement. In this way, the groups take various three-dimensional shapes such as the tulip-hat like shape shown in Fig. 2 or a structure like blood vessels.
In addition, according to a new study, once cancer cells become malignant, the control of the force fails and the phenomena such as invasion and metastasis as mentioned above start appearing. We succeeded in stopping the movement of cancer cells by administering medication called calyculin A to the cells of lung cancer and thereby changing the number of phosphoric acids bonded to myosin regulatory light chain.


What Will be Your Next Goal?

 I would like to investigate how the external environment of cells impacts the cells. Recently, I am focusing particularly on the physical conditions (stiffness, dimension, temperature and radiation). For example, I am investigating how the stem cells like ES or iPS cells differentiate into nerves. I found that the cell types, into which the stem cells differentiate, depend on the stiffness of the culture environment. They differentiate into bone cells in a stiff environment and into nerves in a soft environment. By investigating these mechanisms, I hope to make various shapes of tissues through the differentiation of the stem cells into a given cell.


A Message for the Readers!

I majored in physics at university. At graduate school, I conducted research on the mechanisms by which the crystalline structures change depending on temperature. After receiving my doctoral degree, I went to the U.S.A. alone to study liquid crystals in the Department of Chemistry at Massachusetts Institute of Technology. However, I craved biology and ended up jumping into this area of research. In the world of cell biology where many unknowns exist, I continue to be fascinated every day. Even if one changes his or her research field, anything is possible as long as you have passion and curiosity! I encourage you to break into new subjects regardless of your previous experience and discipline.