Learning from Insects
Department of Synthetic and Biological Chemistry, Graduate School of Engineering,
Kyoto University
Professor Masato Umeda[My basic science approach]I still remember my anxiety when I joined a university laboratory and started my first research.
Because already so many researchers have been studying biology by then, and even now, hundredsof thousands of excellent researchers worldwide are doing research, I wondered if there is anything
I can clarify. However, once I began my research, my fears were quickly resolved. We didn’t
understand so many things about living things, and the laboratory was full of questions that
couldn't be solved and experiments that didn't go as expected. It was well preserved in the headof my mentors who taught me the research and in the laboratory notebooks stored in the laboratory.
These unsuccessful experiments prevented us from repeating the same mistakes and served as astarting point for the subsequent investigation and clues to new discoveries.
Because living organisms are so complex and work in mechanisms beyond our imagination,even if we start a project with a certain hypothesis (goal) and spend a long time conducting a seriesof experiments, we often fail to prove the hypothesis. When we submit such research to so-called
top-notch scientific journals in the U.S. and Europe, most of them are rejected for publication
because the biological significance of the research results is not clear. However, if the research
direction is clear and describes solid facts, it can surely be published in some research journals.
If you have what is called a "fall but don't get up for free" mentality, you can still publish the facts
obtained from your experiments and preserve and share them as an intellectual property forever.
Even scientific journals such as PLOS ONE (Public Library of Science One), which anyone canread without paying a subscription fee and is widely shared by the community, are now publishingarticles as "Positively Negative" articles about the results of unsuccessful drug trials andepidemiological experiments.
Basic science takes time. Sometimes, you may feel discouraged. One of the reasons why we
can continue despite this is that there is a community of scientists who share the facts discovered
during their research as achievements. In this case, finding such a fact is itself an important result,and sharing it with other researchers in the same field can serve as a foundation for the subsequentdevelopment. It may also be true for companies to work hard for years until the results meet
expectations. In such cases, if the CTO and others create a culture in which failures are sharedas important facts, so to speak, and recognized as achievements, the same mistakes will not be
made, and aspiring people will be able to recover and continue their efforts even if they are about
to break.

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[About my research]
It is thought that there are more than 10 million species of organisms living on the earth today,
and we humans, as one of the animal species, live together with many other organisms. Recently,
many scientists were surprised to learn that a great variety of organisms, including bacteria, live
inside our bodies (e.g., in the large intestine) and on our body surfaces and that the number ofsuch organisms is more than ten times greater than the number of cells that make up our entirebodies.

It has also been shown that an imbalance of symbiotic bacteria can trigger various

diseases such as obesity, cancer, and neurological disorders.

This fact revealed by modern

biology indicates that we do not exist as a unique life form, the primate of all things, but as a
symbiosis of many organisms. In order for human beings to survive for a long time to come andlead healthy lives, it is essential to clarify the mechanisms and activities of humans and various
other organisms, which is one of the major challenges for basic biologists.
Insects are the most diversified and thriving animal species on earth, accounting for 60% of
all multicellular organisms. The reasons that insects have thrived in this way are 1) superior
environmental adaptability, 2) miniaturization and acquisition of flying ability, and 3) theachievement of high energy metabolic activity that supports flight. On the other hand, all livingorganisms are composed of molecules such as proteins and lipids created by the combination of alimited number of atoms such as carbon, hydrogen, and oxygen, and tens of thousands of different
chemical reaction systems come together to produce the energy necessary for vital activities. So
what mechanisms do insects have that are different from ours? For example, as shown in thefigure below, an insect less than 1 mm in length, almost the same as a unicellular animal, aparamecium, has the same internal organs, such as brain, heart, and intestines, as we have. How
are these microscopic insects formed? Using Drosophila as a material, our research aims to reveal
the secret of insect prosperity by unraveling its molecular mechanisms. Our research to date has
demonstrated the ingenious mechanisms of the organism, as shown in the figure below.
Learning from Insects
Ultra-small Insects

Factors contributing to insect prosperity
1. high adaptability to temperature: acquisition ofsuperior thermoregulatory mechanisms and systems tomaintain cellular functions over a wide temperaturerange
2. miniaturization and acquisition of flying ability:
acquisition of high cell deformability through uniquemembrane lipid mechanisms
3. high energy metabolism: energy metabolism via
multiple fatty acid transport pathways to mitochondria

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Below is a brief description of each study.
(1) Excellent temperature adaptability
Even insects regulate their body temperature by going to the sun or shade.

We created aheat-loving mutant (atsugari mutant) that always likes to be in the cold and investigated why it
prefers to be in the cold. As a result, we found that the atsugari mutant is highly metabolically
active and that Drosophila goes to cold places when its metabolic energy is high and goes to warm
places when its energy is low, thereby regulating its body temperature according to its body state(Science 323:1740, 2009). We mammals must constantly eat sufficient food (other organisms).
Otherwise, our body temperature will drop, and we will die. In this sense, we are highly flabby
creatures, but Drosophila can live in a wide range of temperatures from 0 to 30 degrees Celsius
and can be considered an energy-saving, environmentally friendly animal that changes its bodytemperature according to its physical condition.
(2) Secret of miniaturization
We perform an experiment in which we suck cells with a pipette about 1 micron in diameter
to measure the activity of ion channels on the cell membrane. What surprised us was that insect
cells were deformed and sucked into that pipette.

Mammalian cells are either not sucked intosuch a pipette at all, or the cell membrane is ruptured if sucked too hard. This observation
prompted us to analyze how the membranes of insect and mammalian cells differ in detail at themolecular level. First, we found that the tension of insect cell membranes is less than 1/10 thatof mammals, making them incredibly soft and viscoelastic.

Furthermore, we discovered that

insect cells have a unique protein that constantly flips the lipid molecules that make up the cell
membrane in and out of the membrane. It was also found that when this protein is deficient, thecells do not deform as rigidly as mammalian cells.

Since cells with this unique property areobserved only in small insects, we hypothesize that acquiring a viscoelastic cell membrane withexcellent deformability may be advantageous for producing the microscopic body tissues necessary
for miniaturization.
(3) High energy metabolic activity
We produce energy by burning lipids called fatty acids in intracellular organelles called
mitochondria. A protein called CPT1 functions as a gatekeeper to transport these fatty acids tothe mitochondria, and if this protein is deficient, the mammal will die. However, in Drosophila,
we found that the animal is completely healthy even without the CPT1 protein and shows noabnormalities in energy metabolism.

This observation implies that Drosophila has anothermechanism besides CPT1 to transport fatty acids to the mitochondria.

Therefore, weinvestigated a series of genes and found new candidate transport proteins. Insects produce morethan a hundred times more energy per unit weight than humans during flight. And the enzyme
CPT1 regulates fatty acid transport through a very complex reaction. Still, this pathway alone isCopyright © Ohsumi Frontier Science Foundation. All Rights Reserved.

not sufficient to provide energy during flight, and we believe that energy is efficiently produced
through the protein we have identified.

In fact, humans have a similar protein, but it has notbeen well studied yet, so we will also try to clarify its function in the future.

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