Background

All cells fine tune their metabolic activity to maintain homeostasis by sensing and responding to intra- and extracellular perturbations. This necessitates a dynamic regulation of signaling and trafficking networks.  Lysosomal function is one of the critical components for organismal homeostasis, and mutations in lysosomal genes cause severe diseases known as lysosomal storage diseases. Similarly, lysosomal dysfunction is emerging as a major hallmark in age-associated diseases including cancer, neurodegeneration and metabolic syndrome. Yet, it is unclear how lysosomal dysfunction affects other components of the cellular machinery and the general subcellular organization, as well as how the dynamic networks in cells compensate for the problems in one organelle.

Project

In this project, we aim to answer two fundamental questions to establish how cells integrate internal and external factors to respond to perturbations or stress; 1) How do the morphology and dynamic network of organelles change in response to stress? and 2) How does this change in organellar morphology reflect cellular response and subcellular organization? To achieve this, our labs will develop and apply new tools to understand how the communication between cellular compartments is altered under various metabolic states and disease conditions. We aim to create a catalog of these alterations in patient-derived cells and cell-based models of neurodegenerative diseases using next generation imaging approaches and omics tools by combining the expertise of the Abu-Remaileh Lab at Stanford and the Saka Group at EMBL Heidelberg.  

References:

^{1. Abu-Remaileh M., et al. “Lysosomal metabolomics reveals V-ATPase- and mTOR-dependent regulation of amino acid efflux from lysosomes.” Science (2017).}

^{2. Saka, Sinem K., et al. “Immuno-SABER enables highly multiplexed and amplified protein imaging in tissues.” Nature biotechnology 37.9 (2019): 1080-1090.}

^{3. Kishi, J.Y. et al. Light-Seq: light-directed in situ barcoding of biomolecules in fixed cells and tissues for spatially indexed sequencing. Nat Methods (2022).} 

^{3. Laqtom N.N. et al,. CLN3 is required for the clearance of glycerophosphodiesters from lysosomes. Nature (2022).}

Find out more:

Interested in finding out more about utilizing new methods to understand the organization and interactions of subcellular compartments? Get in touch, we would love to hear from you!