Mistress of the Keys

Maria Fyta uses gold and diamonds to decipher genotypes.
[Photo: Universität Stuttgart/Uli Regenscheit]

Just one of approximately 10,500 woman professors in Germany: Dr. Maria Fyta, a Junior Professor since March 2012 at the University of Stuttgart’s Institute for computer Physics. That puts her among the approximately 23 percent of women professors recently counted by the Federal Office of Statistics. For her part, Fyta finds such questions of statistics and gender secondary. Rather, she has allowed herself from the very beginning to be guided by her own interests. And this has paid off: her research in deciphering DNA has led her and her team to a notable breakthrough with the help of gold and diamonds.

The DNA of the human body is more than just a little bit long; to be more precise, the DNA chain in only a single human cell is about three meters long. What’s more, this DNA contains millions of so-called nucleo-bases: adenine (A), guanine (G), Cytosine (C), and Thymine (T). How they are lined up in the DNA building blocks determines ‘Whether - to put it simply - we are talking about the genotype of a human being, a banana, or a daisy’, is how Maria Fyta explains it. Techniques for identifying such chains and thus deciphering DNA have been around for some time now - the human genotype was first identified in 2003. The technique for doing so, however, is still very time-consuming and expensive. This was one more reason for Fyta to tackle the issue. She is now part of a vast community of worldwide researchers who are analyzing DNA with one major goal: to read out the entire human genome in only a few hours. That would make it possible, for example, to personalize medical care and tailor it exactly to the needs of the respective patient.

One of the most promising methods for accelerating the analysis of DNA is precisely nanopore sequencing, a technique on which Fyta is presently at work with her research colleagues Prof. Ralph Scheicher (from Sweden), Prof. Rodrigo Amorim (Brazil) and doctoral student Ganesh Sivaraman at the University of Stuttgart.

Jun.-Prof. Maria Fyta
Jun.-Prof. Maria Fyta

„Tireless curiosity, a love of combining things to see what works best - those are character elements that must be firmly anchored in the DNA chain of every scientist.“

Junior Professor Maria Fyta

Threading the needle with DNA

The technique requires pulling a strand of DNA through a nearly infinitesimally small hole in an artificial membrane - much like threading a needle. For their part, the membranes consist of biological or synthetic materials and have a high level of electrical resistance. Fyta works with membranes of silicon nitride or graphene in an electrically charged salt solution. In contrast to normal ion channels, the nanopores are permanently open and allow a constant flow of molecules through the membranes. The ions move from one side of the membrane to the other, generating electrical current. The amperage changes measurably each time the four different DNA bases A, G, C and T move through the nanopores.

This can in turn be very quickly read out via gold electrodes positioned in the nanopores. But it wasn’t easy: ‘We were looking for a way to prevent a signal overlap from the nucleobases or from the salt solution which surrounds them, since that would have falsified the results,’ says Fyta. To give an idea of the overlap: it is as if individual letters of the alphabet were to merge into one another until the word is no longer decipherable. The solution, as Junior Professor Fyta explains, was: diamonds. ‘To keep the signals from getting mixed up, we modified the gold electrodes with an additional layer of diamonds. It turned out to be the breakthrough we were hoping for, because it changed the interaction between DNA and nanopores. We found that the signal changes radically, depending on which nucleobase is being pulled through the nanopores at any given moment.’

Nanoporen mit goldenen Elektroden und diamantenen Spitzen können möglicherweise den genetischen Code entschlüsseln.
Diamond-tipped nanopores with gold electrodes may have the capacity to decipher the genetic code.

It took physicist Fyta and her team a good three years of research to announce their first successful trials in June of 2016. ‘But we’re nowhere near the end of our research’, she says. ‘This discovery has remained purely theoretical in nature up to now. Now we must fine-tune our observations on the computer and then turn our ideas into practical reality. But that’s science, after all: always step by step!’ Step by step: that’s a good way of describing Fyta’s own per- sonal career after her birth in Germany and growing up in Greece. But no matter where she was, she always liked mathematics and physics; and so, after her school graduation she decided to get a university degree in physics. She herself has the very qualities she describes as part of every scientist’s DNA chain: tireless curiosity and a love of combining things to see what works best. Those are essential elements ‘in the DNA chain of every scientist,’ she says again, but now, as a 39-year-old mother of three children, with a gleam of humor in her eye. Her Master’s Degree was followed by a doctorate at the University of Crete, whence her studies took her to Boston in the U.S.A., where she began her research on nanopores in 2005. But success has spoiled neither Maria Fyta’s curiosity nor her interest in other issues. She is also fascinated by the sciences of solid body and material physics, where, for example, she is pursuing the question of how to determine the characteristics of materials and what happens when she changes their structure or their chemical features.

For Fyta, the exploration and discovery of new topic areas is part and parcel of her career: ‘Time and again they provide the inspiration for other projects.’ Just one example: her interest in research into small diamonds ultimately led her to experiment with the characteristics of nanopore sequencing. The upshot is that there’s no saying what new fields of science this Junior Professor will hit upon in future for herself. What does she herself say? ‘A true researcher dies in his boots. All my projects have the same general direction, but what comes next is always a surprise. And so I try to react flexibly.’ Isn’t that fatiguing and frustrating at times? ‘Not at all!’ says Fyta emphatically. ‘After all, there’s no fun in doing the same thing forever or always knowing what will happen!’ - Michaela Gnann

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