Katerina Naydenova

Cells are continuously challenged by a variety of dangerous cytosolic materials, including invading bacteria, misfolded proteins or damaged organelles. All of these need to be promptly detected, triaged and possibly cleared to ensure maintenance of physiological functions and cell survival. If these pathways fail, the consequences are catastrophic: accumulation of protein aggregates is associated with neurodegenerative diseases such as Alzheimer’s and Parkinson’s; impaired lipid turnover contributes to metabolic syndromes including type 2 diabetes and fatty liver disease; and defective organelle recycling can trigger inflammatory disorders and compromise immune responses. In my current work, I use bacterial infection models, combined with structural biology and biochemical methods, to understand how cells defend themselves against cytosol-invading bacteria. At the same time, it is becoming apparent that the same pathways that survey the cytosol for invading pathogens are also repurposed for danger sensing and resolution in many other physiological contexts. Therefore, I am interested in elucidating the universal and cell-type specific molecular principles that enable cells to detect diverse threats and decide their fate - destroy, recycle, or tolerate. Structural biology is a powerful tool to investigate these mechanisms, but putting protein structures into their cellular context remains challenging. Building on my background in physics and on my previous experience in methods development for electron microscopy (see my Publications page for more details), I continue to design new methods and instruments that extend the limits of what we can see inside cells, enabling experiments that are impossible with existing technologies.