Understanding the real life of microorganisms and the dynamics ofcellular components
Division of Applied Life Sciences, Graduate School of Agriculture,
Kyoto University
Professor Yasuyoshi Sakai[My basic science approach]
Basic biological research, which explores the secrets of life, is slightly different fromengineering research where humans try to design and create something new that does not exist in
the world.
In other words, our research interests are living organisms that have survived over billions ofyears through evolution and have complex functions, shapes, and relationships with each other.
Animals, including humans, eat other living organisms and break down their biologicalcomponents into glucose and amino acids, which are then used as raw materials for the building
blocks of the body while at the same time obtaining energy. On the other hand, plants use photoenergy to synthesize all biomolecules from the lowest energy level compound, CO2.

This isphotosynthesis. Therefore, plants are at the top of the food chain, and other organisms on theearth live on them by consuming their carbon and energy resources. However, this does not meanusing it all at once; instead, our metabolic system can efficiently extract maximum energy step bystep. Even plants, which appear to be able to survive alone, need symbiotic microorganisms orsoil microorganisms to pass their lives on to the next generation.

As described in detail in the"About my research" section below, microorganisms that live in symbiosis with plants werethought to be found underground, like rhizobium bacteria. In reality, however, there aremicroorganisms on the leaves that have important interactions with plants, and they have been
symbiotic and helped plants grow from ancient times without our knowledge.
We need to be honest and humble when investigating these wonders of life.
Successes and failures are because of the assumptions and objectives that the researcher wants
the results to be. In fact, the results of any experiment are "facts," and there are no successes or
failures. In this sense, if the purpose or vision is too distinct, it may blur our instinct when wecome across an unexpected experimental result or discovery.
I think that the intuition needed for discovery is similar to what top jazz musicians feel whenplaying an ad-lib. May I say a "the ambiance" of the stage?
At the first-class ad-lib performance, often the musician utters a cry, feeling something thatexists only in that place and time. To reach such a feeling, I think that not only perfected playing
techniques but also other personal experiences that are seemingly unrelated have great influences.
So to speak, I believe that the process of converting everything, including successes, failures, andhard work, into personal experiences and cultivating sensitivity through them is what prepares usfor discovery in science.

Copyright © Ohsumi Frontier Science Foundation. All Rights Reserved.

[My research]
Although invisible to the naked eye, microorganisms perform various and significant
functions that we are unaware of.

Yeast supports our food culture by helping to produce

fermented foods such as alcohol and bread. Gut bacteria support our health. And the coordinatedmaterial cycle by various microorganisms protects the global environment.

Basic research toexplore their way of life and mechanism has led to many scientific discoveries and has continued
to provide solutions to various problems.
About 50 years ago, a yeast (C1 yeast) that grows by eating a compound called methanol,
which has only one carbon, was found in our laboratory.

Based on basic research on how

methanol is metabolized to obtain energy and assemble all cellular components from a single
carbon, C1 yeast is now indispensable for producing many valuable proteins, various
pharmaceuticals including vaccines, and other industrial enzymes.
Production of human proteins using E. coli cells sometimes fail because of misfolding of theexpressed proteins. On the other hand, since yeast is an eukaryote just like humans, they sharesimilar system of protein synthesis. When the process is set up appropriately, it can produce
proteins with the correct structure.
In the process of studying the "insides" of yeast, we have made several discoveries. When C1
yeast eats methanol, the number of tiny organelles called “peroxisomes” increases and becomessurprisingly large. When the methanol is gone, the peroxisomes are degraded by autophagy.
We have been studying how peroxisomes are formed, how they are enlarged, and conversely, how
they are degraded. Notably, microautophagy, in which vacuoles directly surround and degrade
intracellular organelles, has been found to be driven by a set of genes that are different from thoseso far found in autophagy.
C1 yeast proliferates in nature by feeding on methanol that exists on plant leaves. Methanol
concentration on leaves significantly fluctuates from day to night. C1 yeast regulates the rate ofmethanol intake by balancing the synthesis and degradation of peroxisomes and methanolmetabolizing enzymes in response to these fluctuations.

By investigating why they live go

through such a troublesome procedure in nature, we learn for the first time about the real life of
microorganisms. Such insights give us many hints for both basic and applied researches, such as
for protein production and for overcoming environmental problems.
C1 bacteria that can eat methane and methanol are also known.

C1 bacteria that live on

leaves also give benefits to the plants, such as promoting the plant growth. Many studies have been
conducted on microorganisms that live in the underground parts of plants, typically, rhizobacteria,Copyright © Ohsumi Frontier Science Foundation. All Rights Reserved.

But nothing is known about plant-microorganism interaction of the above-ground parts ofplants, which are greatly affected by diurnal variations in sunlight and temperature.

Although

we are not sure yet where such research will lead us, I enjoy science every day, expecting newexperimental results that will provoke us to new ideas and break-through technologies inincreasing crop yields or in reducing greenhouse gases.
The central theme of our laboratory is to learn from the real life of microorganisms, toessentially understand their functions, to gain hints from them, and to make use of them. This
is not an easy task by any means, but we would like to continue our dialogue with microorganisms.

Dynamics ofReal Life

Cellular Components
C1 Microorganism

C1 Yeast

Peroxisome and C1 YeastDay
Night

C1 Bacteria

Plant and C1 Bacteria

Microautophagy

Elucidation of Mechanism

Tips to Make it UsefulMetabolism
Synthesis & Decomposition

Biological Production

Movement of Intracellular Organelles

Energy and Natural Resources Issues

Plant-Microorganism Interaction

Copyright © Ohsumi Frontier Science Foundation. All Rights Reserved.