There are antibiotic-resistant bacteria causing serious illnesses. To stay alive, many of these bacteria require proteins entangled in nodes or “knots.” These knots, like a loop of line in mountain climbing, stabilize and reinforce the molecules. But Agata Perlińska, a laureate of the 2019 START competition of the Foundation for Polish Science awarded distinction for outstanding research achievement, wants to outsmart nature. What if a molecule could be created blocking the knot that is vital for the proper functioning of the protein? The protein would cease functioning and the bacteria would not survive. According to Perlińska, “That would be a dream antibiotic and a breakthrough in many diseases for which medicine has no cure!”
But before this progress can be achieved, it is essential to learn as much as possible about the knots. What forms can they take and what purpose do they serve? Does each type of knot have a different function in the cell? This is an area being explored by FNP stipend winner Agata Perlińska in her work at the Centre of New Technologies at the University of Warsaw. In this year’s START competition, she was awarded a distinction for outstanding research accomplishments.
Figure-eight knot and the dirty dozen
Knotted lines can stabilize sails and secure mountain climbers. The same mechanism used by children when they learn to tie their shoes also operates in nature. Scientists discovered this just 20 years ago, but have already identified over a thousand molecules with various types of nodes.
Recently the World Health Organization published a list of 12 dangerous bacteria resistant to antibiotics. All of them share a specific enzyme, the protein TrmD. Significantly, this enzyme contains a “knot.” A protein with the same function also occurs in humans, but our enzyme does not have this node.
Agata Perlińska’s research has shown that this “knot” is very active, assisting in reactions essential for the life of the bacteria. If scientists could create a molecule blocking the node, the reaction could not occur. Such a treatment would essentially disarm the bacteria.
The idea sounds simple, but requires many years of analysis and cooperation by scientists all over the world. The young Polish scientist is studying how these nodes affect the functions of the proteins, and the reason for their existence. It is known that they do not arise spontaneously, by accident, because successive generations of organisms also feature such entanglement. Evolution formed these knots and consistently maintains them.
This research requires not only knowledge of the life of the cell, but also fluency in computer programming. Agata Perlińska first studied biology, but when a new programme in bioinformatics and systems biology was created at the University of Warsaw, she began to study there as well, joining the small group of specialists known as “bioinformaticians.” She was fascinated by constructing computer models for molecules, cells and organisms.
Domestic menagerie and hanging gardens
Perlińska participates in scientific meetings and conferences, conducts calculations, and writes publications. With all this going on, it’s hard for her to find time to escape from the city. But the source of her scientific passion lies in her love for nature. Is it frustrating when nature is overshadowed by her work? No, because she has found a perfect solutions: she brought nature home.
Every morning she wakes to the conversation between her parrot and canaries. Two young terriers await their morning walk. They are lucky, and not just because one of them is a stray who was taken in. Mostly because they get plenty of exercise and companionship. They can develop properly because their owner can easily combine her duties as a bioinformatician with taking care of her animals.
“I do a lot research on the computer,” Perlińska explains. “I’m not tied to the lab, but can work at any time and place I choose. This allows me to walk the dogs when they need to go out, and for as long as they want. We like to run together in the park near home.”
Happy, healthy dogs radiate energy she can then put to use in many hours of bioinformatic analysis. She takes additional satisfaction in growing vegetables and grapevines. Living on the first floor of an apartment block is no hindrance. After all, what are balconies for?
“I enjoy urban gardening,” Perlińska said. “I cultivate edible plants: tomatoes, radishes, grapes…. I also encourage my family to try it. It’s enough to get them to sample the fruits and vegetables I raise. They’re especially tasty, and the garden in full bloom makes an impressive sight. A big balcony is convenient, but dwarf varieties of tomatoes can be grown even in pots on the window sill. You just have to water them, and later they provide a great treat.”
Will Agata Perlińska’s research also bear fruit? Will it help other scientists create new antibiotics? There’s a great chance that it will. After all, each of the “dirty dozen” most antibiotic-resistant bacteria share the same enzyme that the young researcher is closely examining.