About

Proteins are remarkably fine-tuned molecular machines, precisely sensing and responding to their environment. Our lab aims to decipher the structural and functional mechanisms that enable this dynamic decision-making, with the broader goal of applying these insights to artificial protein design. To achieve this, we focus on two contrasting model systems: the highly flexible AAA+ ATPase from Mycobacteria, which drives protein degradation, and the structurally rigid iron-storage protein ferritin, along with the dynamic network of flexible and disordered proteins that regulate its fate in the cell. By integrating Cryo-EM with functional assays, we unravel how these molecular machines operate at atomic resolution. Our interdisciplinary team—bringing together biologists, chemists, and physicists—fosters a collaborative atmosphere where members develop both intellectually and technically. The lab is also a key contributor to advancing Cryo-EM as a major scientific resource for the Israeli research community.

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Model Systems

Our lab focuses on two complementary model systems that illustrate how proteins integrate environmental signals to make functional decisions:

AAA+ ATPases 
  We study Mpa, the proteasomal ATPase of Mycobacteria. Mpa is a highly dynamic molecular machine that orchestrates substrate identification, unfolding, and translocation into the 20S proteasome. This system exemplifies how proteins integrate mechanical, structural, and nucleotide-derived signals to regulate substrate processing—a key decision in proteostasis.
  Mpa is essential for the survival and virulence of M. tuberculosis, making it a promising target for novel antibacterial strategies.

Iron Homeostasis
  We investigate the iron-storage protein ferritin and its regulation by the adaptor protein NCOA4 and the E3 ubiquitin ligase HERC2, which together form the Ferritin–NCOA4–HERC2 iron regulatory circuit. This network controls ferritin degradation in response to fluctuations in intracellular iron levels and redox state, integrating metabolic, oxidative, and signaling cues to regulate iron availability.
  Dysregulation of this circuit is implicated in conditions such as neurodegeneration, anemia, and cancer, underscoring its importance in both cellular function and human health.