Exploring Diseases through the “Alarm System” in Our Body
Akinori Takaoka , Professor
Division of Signaling in Cancer and Immunology, Institute for Genetic Medicine, and Graduate School of Chemical Science and Engineering.
High school : Hokkaido Prefectural Asahikawa East High School
Academic background : Medical Science Doctorate from Sapporo Medical University
- Research areas
- molecular immunology
- Research keywords
- infection, microorganisms, pattern recognition receptor, natural immunity, signaling, nucleic acid (DNA/RNA), virus infection
What do you study?
Looking back at our history (Figure 1), traces of tuberculosis have been discovered in ancient Egyptian mummies. It is believed that Alexander the Great of Macedonia died of malaria during an expedition to India. In the 14th century, plague claimed the lives of more than one third of the entire population of Europe. The right eye of Masamune Date, a Japanese warrior in the Sengoku period known as “Dokugan-ryu (one-eyed-dragon),” is believed to have been damaged due to smallpox suffered in childhood. All these diseases are referred to as infections, which are caused by pathogenic microbes invading the body. As such, small invisible creatures have had a sufficiently large impact on human activities for us to say that our history is to some extent one of fighting various microorganisms.
Our fight against microorganisms goes on and through recent measles and flu epidemics, as well as the arrival of new viruses such as SARS (severe acute respiratory syndrome), we are actually now witnesses to life-threatening situations. I wish to somehow control these infections. The first step of infection is when microorganisms cross the line and invade our body. How does our body recognize the invasion of such microorganisms? We will focus on our “alarm system.” In our daily lives, security measures are taken by sounding alarms through surveillance cameras, thereby immediately informing us of burglaries (Figure 2).
In fact, it is currently known that such an alarm system exists in our body as well, informing us of the invasion of pathogenic microbes. Of course, we do not have resident “dwarf” security guards that patrol our body. However, it has been revealed that multiple protein sensor molecules referred to as pattern recognition receptors exist. The alarm system goes off when these receptors recognize the lipid and protein molecules comprising the cell wall, outer membrane, and flagella of invading bacteria.
Oddly, we are born with a system that monitors the invasion of microorganisms including bacteria and viruses on a round-the-clock basis, awake or asleep, with the pattern recognition receptors playing the central role. This is the first step of our immune response (innate immunity). My research involves analyzing the mechanism of innate immunity at a molecular level. Turning ON the innate immunity switch also leads to the potent induction of more specific adaptive immunity activated thereafter, enabling the efficient elimination of invading pathogenic microbes. Therefore, I believe elucidating the activation mechanism of this innate immunity is research of great importance in controlling infections. Furthermore, in addition to detecting the invasion of microorganisms, pattern recognition receptors also detect other dangers and abnormalities in our body, revealing that they are associated with diseases such as inflammatory diseases, autoimmune diseases, and cancers.
What is the aim of your research?
While nucleic acids such as DNA and RNA make up the original so-called “blueprint of life” of genetic information, interestingly, nucleic acids derived from affected microorganisms (viruses and bacteria) become the target of pattern recognition receptors, leading to the activation of innate immunity. Our research group has identified a candidate protein sensor molecule which serves as the alarm system associated with DNA recognition in the cell. It was revealed that such nucleic acid recognition sensor molecules activate the signaling pathways in cells once they detect nucleic acids derived from invading microorganisms, leading to the production of a soluble factor with anti-viral activities referred to as interferons, thereby strengthening the resistance of cells to viruses (Figure 3). Through elucidating these mechanisms in detail, our goal is to contribute to the development of novel treatment drugs and prophylactics for virus infections such as colds and the flu (Figure 4). Furthermore, by advancing research from this new perspective of an internal “alarm system,” we aim to proceed with basic research which will be useful in saving many patients suffering from immune diseases and cancers.
About the Institute for Genetic Medicine
The Institute for Genetic Medicine, to which I belong, has more than 10 laboratories and auxiliary facilities; specifically, research contributing to the diagnosis, prevention, and treatment of diseases is carried out. If you are interested, I look forward to studying with you! Institute website: http://www.igm.hokudai.ac.jp/english/index.html
TAKAOKA Akinori and TANIGUCHI Tadatsugu. “Cytosolic DNA recognition for triggering innate immune responses.” Advanced Drug Delivery Reviews; 60:847-857 (2008)