The truths of life as described by analytical chemistry

Advances in analytical chemistry have pushed forward the frontiers of life sciences.
Now that the actors within the cell are becoming revealed, analytical chemistry will step into a new realm.

Analytical chemistry is the analysis of certain materials to gain an understanding of their chemical components and their quantities. Advances in analytical chemistry, such as gene analysis using a DNA sequencer and protein analysis by mass spectrometry, have brought significant breakthroughs to life sciences.

Professor Ozawa of the Analytical Chemistry Lab has devoted more than twenty years of research to in vivo molecular imaging to directly visualize the dynamics of biomolecules within the living cell. His first encounter with this research was in 1997 when he was a doctoral student.

“I was fascinated by the GFP imaging technique, a technique to label calcium ions with green fluorescent protein (GFP) to observe how the ions work spatiotemporally within the cell. I will never forget the excitement I felt when I first saw those cells glowing in green under the microscope. They looked like stars shining in the sky, and I could also clearly see the motions of the molecules.”

Ever since, fluorescent imaging using GFP has become an important part of his research. In addition, he has been working on developing a new visualization technique in recent years.

When light is radiated on a material, it interacts with the molecules and scatters as light with a different wavelength from the original incident light. This is called Raman scattering. Since each molecule has a unique vibrational frequency, analysis of the spectral information in the scattering light will allow us to identify what kinds of molecules are present in what amounts in a given space. Professor Ozawa is committed to the development of this Raman imaging technique.

“We have gained quite a lot of information about who the ‘actors’ are; that is, what molecules are active within the cell. Our next step is to learn more about how these actors interact with each other to be able to quantitatively describe the molecular network and reactions. The movements of proteins and calcium ions can be captured with fluorescent imaging, while lipids, hormones, and metabolic products within the cell can be identified with Raman imaging. I believe we will be able to elucidate the interactions between various molecules by using both techniques at the same time.”

Professor Ozawa is also working to develop new technologies by applying these intracellular visualization techniques. One such technology is a protein identification by library screening. Receptors on the cell membrane called G-protein coupled receptors (GPCR) are associated with various diseases and researchers are searching for chemicals that will inhibit their function as potential candidates for drug development. Building on intracellular visualization techniques, he has developed a unique technology to efficiently identify GPCR inhibitors.

Another example is a technology born from an innovative concept going far beyond the boundaries of conventional analytical chemistry. The basic idea is to control the activity of enzymes (proteins) in the cell by using light. By connecting the target enzyme with a plant-originated protein that responds to light, enzyme activity can be switched on or off in response to light stimulus. Using this technology, it will be possible to closely observe the reactions an enzyme induces in the cell.

“The technologies we have today will sooner or later be replaced with new technologies in the future,” Professor Ozawa said when looking back on his past work. “What really counts is to develop a new concept. A fundamental concept will be passed down, leaving a mark in history. This is the best part about science. The desire to understand the origins of natural phenomena is what led me to a career in science and what continues to fascinate me even now.”

Interview and text: Masatsugu Kayahara
Photography: Junichi Kaizuka

Originally published in The School of Science Brochure 2019

Takeaki Ozawa

Professor, Department of Chemistry
Professor, Department of Biological Sciences (joint appointment)

Graduated from the Department of Chemistry, Faculty of Science, The University of Tokyo in 1993. After completing his PhD at the Department of Chemistry, Graduate School of Science, The University of Tokyo in 1998, he served as a research associate (1998-2002) and lecturer (2002-2005) at the Department of Chemistry, School of Science, The University of Tokyo. In 2005, he was appointed as an associate professor at the Department of Molecular Structure, Institute of Molecular Science. He has held his current position as a professor at the Department of Chemistry, School of Science since 2007. In 2014, he was concurrently appointed as a professor of the Department of Biological Sciences, Graduate School of Science.