A major focus of our research is neuronal morphology, because neuronal shape is a key determinant of function. To better understand the molecular mechanisms underlying neuronal development, we study the function of the mTOR kinase. However, neuronal architecture changes not only during development but also during aging and disease processes in the adult brain, including depression. For this reason, in recent years we have also focused on molecular mechanisms that stabilize dendrites and on how this stability is disrupted in the mature nervous system. 

Research Summary 

Since the establishment of the laboratory, we have studied the role of the mTOR kinase in neurons, particularly in nervous system development. Dysregulation of mTOR activity leads to neurodevelopmental disorders such as tuberous sclerosis complex. mTOR is a central regulator of cellular metabolism: it integrates information about cellular energy status, amino acid availability, and extracellular signals, including trophic factors. 

In recent years, our work has addressed mTOR-dependent processes such as translation, transcription, autophagy, and intracellular trafficking. All of these processes are important for proper neuronal development and function. We now focus particularly on mTOR functions in the cell nucleus - a non-canonical and still poorly characterized localization. We have shown that in neurons, mTOR accumulates in the nucleus in response to increased neuronal activity. 

In parallel, we study mechanisms responsible for the stability of mature neuronal morphology. In this area, we identified mTOR as one of the key regulators. We have also discovered new proteins involved in stabilizing neuronal architecture, including ITPKA, whose molecular functions in this context are now under investigation.

Scientific Impact 

• Demonstrating that inhibition of mTOR activity via activation of autophagy regulates lysosome transport along microtubules. 
• Identifying dilazep and penbutolol through screening approaches as candidate antidepressant compounds; a patent application is pending. 
• Advancing knowledge of non-canonical functions of mTOR in the neuronal cell nucleus. 
• Identifying new proteins involved in dendritic stabilization and destabilization in the adult nervous system

Future Goals

Our main goal for the coming years is the comprehensive characterization of nuclear mTOR in brain development, physiology, and pathology. We aim to determine how this non-canonical pool of mTOR affects neuronal function and how its disruption may contribute to diseases of the nervous system. 

In parallel, we will continue to investigate the molecular mechanisms controlling dendritic stability and destabilization in the adult nervous system, particularly in the context of depression and other disorders associated with altered neuronal architecture. 

Collaborations

Our key collaborators include Prof. Kathrin Thedieck, Prof. Sergiusz Jóźwiak, Prof. Katarzyna Kotulska, Prof. David Kwiatkowski, Prof. Eleonora Aronica, Prof. Leszek Kaczmarek, and Prof. Ewelina Knapska. Together, we work to understand how molecular mechanisms translate into clinical features of tuberous sclerosis complex and depression, and how this knowledge can be used to help patients. 

Awards and Recognition 

2020 - Polish Prime Minister Award for scientific achievement
2021 - 2nd Division (Biological Sciences) of Polish Academy of Sciences Award for a series of publications on mTOR and novel therapeutic targets in TSC
2023 - election to the European Molecular Biology Organization
2024 - Herbert Resner Award for research that demonstrated a potential new therapy for tuberous sclerosis.
2025 - election to the Polish Academy of Sciences 

Comment

"Our research focuses on the molecular basis of the development and stability of neuronal networks. In particular, we focus on the molecular functions of the mTOR protein, which may enable better diagnosis and potential therapy of mTORopathies, diseases caused by mTOR hyperactivity," says Prof. Jacek Jaworski.

Rat hippocampal neurons cultured in vitro. Immunofluorescence labeling shows GluA1 in green, Bassoon in red, and cell nuclei in blue. Illustration by Karolina Protokowicz.