The effect of individual proteins never ceases to amaze Daria Siekhaus. In fruit flies, she searches for molecules whose counterparts in humans play a role in diseases such as cancer or Alzheimer’s.
“Energy production is the basis of everything,” says Daria Siekhaus. However, she is not talking regarding the gas crisis or renewable energies, but regarding our bodies and every single cell. The power plants in them are called mitochondria: the better these organelles and their cell respiration function, the more energy is available to the cells and the body.
“My interest in science was awakened when I was a baby,” says Siekhaus, who grew up in Berkeley, USA, as a child of German parents. Her father was a scientist, he inspired his daughter from an early age for the unsolved questions of the world. “My first words were: ‘What’s that?'” Siekhaus laughs in the interview. Shaped by a Catholic family, religion, spirituality and an interest in research are not contradictory for her: “Our experiments are like a conversation with God: If you want to get answers as to why the world is the way it is, you just have to get the right ones Ask questions. Every result is an answer.”
The Persian Queen Atossa
Mythology and ancient history also play a part in Siekhaus’ current work, which Institute of Science and Technology Austria (Ista) heads a group in the field of life sciences in Klosterneuburg. Your Iranian employee Shamsi Emtenani named the recently discovered protein, which provides more energy in the mitochondria, following the Persian queen Atossa. Herodotus wrote regarding Atossa: “She got everything she wanted.” That goes well with the protein that ignites a turbo in the cells – and practically gets his way.
“With the additional energy, immune cells manage to penetrate the tissue,” explains Siekhaus. The research takes place on macrophages, the large immune cells that travel long distances in the body to render invaders such as viruses and bacteria harmless.
Serve as a model organism fruit flies, Drosophila. “These are exactly the flies that buzz around the fruit in the kitchen. Their immune system is very simplified, we can use them to study a lot that also applies to us humans,” says Siekhaus.
While the human immune system is made up of dozens of cell types, 90 percent of the immune cells in a fruit fly are macrophages, whose molecular signaling pathways are very similar to ours. “One of the neglected questions regarding the movement of cells is how immune cells move three-dimensionally in the body and how they penetrate tissue,” says Siekhaus. Her team has now published in the journal EMBOthat the Atossa protein provides more energy in the macrophages in two ways: “First, Atossa steps on the gas pedal and supplies the mitochondria with more fuel. Secondly, this fuel, which is sugar and fat, can be better utilized.” So Atossa shifts up a gear in the production of proteins, which ensure that the fuel is converted into the energy substance ATP in the mitochondria. (explanatory video on Youtube)
That’s how it works in cancer cells
These findings are not only useful for immunology, but also for cancer research: “What we find in immune cells is often the same in cancer cells. Here, too, an increased function of the mitochondria plays a role in how cells can migrate and invade tissue,” says Siekhaus.
Her colleague Marko Roblek even discovered a protein that restricts the movement of cancer cells and can thus prevent the spread of metastases. This novelty was not given a royal name because the protein from fruit fly research already had its name: MFSD1. But the value of the finding should not be underestimated: in mice with breast, colon and skin cancer, MFSD1 was important in preventing the tumor from migrating and spreading. A lack of this protein led to more robust cancer cells that form more metastases.
A comparison with patient data published by research colleagues from St. Pölten shows that MFSD1 may be able to show how a cancer develops as a biomarker in the future. “Our goal is always the application in medicine. Of course it takes many years, but step by step we are getting closer,” says Siekhaus.
The Atossa research should also be relevant for the application: The equivalent proteins in humans might influence neurodegenerative diseases such as Alzheimer’s.
A mutation changes everything
In any case, every look into the microscope and into the laboratory dishes confirms the enthusiasm that Siekhaus felt even as a young student in the USA: “Ever since I heard that a single mutation in a protein led to a fly instead of an antenna As my leg grows, I also try to find out which proteins and mutations have such a big effect.” Her position at the Ista in Klosterneuburg will end next year, but Siekhaus will continue the search for the secrets of nature. Where? She doesn’t know that yet.
Dictionary
macrophages are white blood cells and part of the immune system. They are also called scavenger cells because they basically eat up unwanted cells in the body. The macrophages enclose the virus or bacteria and break down the pathogens.
mitochondria are organelles in our cells called power plants. Energy is produced in the mitochondria in the form of ATP (adenosine triphosphate). The high-energy molecule gives the cells the power to move and work.
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