Dr. Natalia Kononenko
Associate Professor and Group Leader at University Hospital Cologne, Germany
Postdoctoral fellow University of Berlin, Kavli Institute for Systems Neuroscience, Norway & Charité Medical School, Berlin
PhD Russian Academy of Science
Dr. Natalia Kononenko had a “love at first lecture” experience when she was introduced to the idea of synapses in a biophysics class at Kaliningrad State University in Russia. She was immediately fascinated by these structures that underlie so much of the brain's inner workings. To this day, Natalia remains just as passionate about synapses as she was during that first biophysics lecture. Now she is a principal investigator at the Cluster of Excellence in Aging Research at the University of Cologne and her lab studies the cellular and molecular mechanisms of neurodegeneration.
After that fateful lecture, Natalia maintained her fascination with the human brain. When she had to pick a specialization at the end of her third year of university, she chose to do research in the lab of the same biophysics professor who had introduced her to synapses, Dr. Valery Zhukov. It was the only lab working on synaptic physiology in Kaliningrad. Zhukov’s lab was using pond snails as a model to study synaptic transmission and neurotransmitter release, with one small caveat. The students in the lab had to collect their own snails from the ponds around Kaliningrad before starting experiments! In the lab, Natalia discovered she enjoyed many components of research, like analytical problem solving, writing, and performing experiments and thus decided to pursue a PhD.
Natalia continued working in the Zhukov lab for her PhD. At the time in Russia, PhD students received a stipend of about ten euros a month. To afford living expenses, Natalia had to wake up at four am every day to work a second job cleaning offices, and then afterwards would head to the lab. In the lab, she performed EMG recordings that allowed her to monitor the muscle responses in snails while pharmacologically manipulating different neurotransmitter receptors to determine which were involved in the defense reflex. Partway through her PhD, Natalia participated in a German DAAD exchange program in which she received a three-month grant to work in an electron microscopy lab in Göttingen. She was overjoyed when she saw synapses for the first time at the resolution offered by electron microscopy. Combining her EMG recordings and her electron microscopy data, Natalia determined that the defense reflex in snails is mediated by multiple neurotransmitters, which were unexpectedly often being released at the same synapses.
After her PhD, Natalia moved to western Europe to begin her postdoctoral training. First, with the support of a prestigious postdoctoral Alexander von Humboldt fellowship award, she moved to Berlin to work in the lab of Dr. Hans-Joachim Pflüger. When she moved to Germany, she was shocked to learn that graduate students got paid a living wage and didn’t have to work supplemental jobs, in stark contrast to her experience in Russia. This solidified her decision to permanently leave Russia to pursue an economically viable career in research.
After her first postdoc studying neuromodulation in the spinal cord and brain of locusts, Natalia decided she wanted to change research focus to study neurodegeneration. She found a second postdoctoral position in Trondheim, Norway in the lab of Dr. Menno Witter studying neuronal circuits involved in navigation in rats. While there was some technical overlap between this new line of work and her prior work in locusts, she was also exposed to several techniques that were brand new to her, including stereotactic surgeries and working with rats. In her research, Natalia found that cells from the ventral retrosplenial cortex provide input to the presubiculum. The presubiculum contains neurons that encode head direction (head-direction cells) and location (grid cells) and are critical to navigation. Given that the presubiculum is important to spatial learning and memory, Natalia and her co-authors argued that this pathway explains why manipulations of the retrosplenial cortex affect spatial navigation and memory. During this postdoc, Natalia became fascinated with the heterogeneity of cell types and regions in the brain, something she continues to study in her own lab.
Although Natalia immensely enjoyed the research in her second postdoc, she left after two years because she wasn't enjoying life outside the lab in Norway. She found her third postdoc back in Germany, in the lab of Dr. Volker Haucke at the Charité Medical School & Leibniz-Institute for Molecular Pharmacology. In this postdoc, she studied the process by which synaptic vesicles are recycled at the presynapse. Historically, it was postulated that this process was dependent on a protein called clathrin. Via its concertation at the plasma membrane, clathrin induces changes in membrane curvature, and then pinches off as a spherical vesicle. However, this process is quite slow and could potentially be rate-limiting in a quickly firing neuron. Natalia found that mammalian neurons have evolved a faster, clathrin-independent mechanism for uncoupling membrane retrieval and vesicle formation, allowing the cells to cope with membrane expansion without necessarily remaking synaptic vesicles at the same speed.
After her third post-doc, Natalia was offered and accepted a position as a research group leader at the CECAD cluster of Excellence at the University of Cologne, a major hub of aging research in the world. As an independent PI, she was entrusted with the task of setting up a brand new laboratory, including purchasing all the lab equipment and taking care of administrative matters such as employment contracts for hiring staff, which was quite a challenge for her management skills. Furthermore, although Natalia loves running a lab and enjoys science immensely, being a mother and running a lab is a balancing act. Having a job with long and often inflexible hours (due to her teaching load) is challenging, and she is often left without easy mechanisms to take a day off if her child is sick. While the process of starting a lab was an incredibly intense challenge, being so independent also comes with the advantage of having a lot of control over her research direction and experiments.
At the University of Cologne, Natalia’s research focuses on several different directions. First, her lab works on non-canonical functions of autophagy and endocytosis. Natalia’s lab has discovered that if you inhibit endocytosis in cerebellar Purkinje cells, you intriguingly end up with an overabundance of synapses and a misbalance of climbing and parallel fibers, causing massive disruption to the cerebellar network, and eventually cell death and ataxia. Her group has also been working on metabolic rewiring in neurodegenerative diseases, studying the impact of different diets during aging and assessing their impacts on autophagy.
If Natalia weren’t doing science, she likes to imagine that she would be a criminal investigator or a classical literature translator, solving puzzles and using her analytical skills. Although she certainly would have excelled in any of these fields, we’re glad that, at least for the moment, she has chosen to lend her analytical acuity to neuroscience research, and we are certain that Natalia and her research group will uncover many more fascinating connections and biological phenomena.
Find out more about Natalia and her lab’s research here.
Listen to Margarida’s full interview with Natalia on December 6, 2024 below!
