Présentation
Date : 5th June 2025 10am
Speaker : Yamuna Krishnan (Department of Chemistry, University of Chicago)
Title : Intracellular Electrophysiology
Location : Room Jules Bordet (Metchnikoff)
Abstract :
The chemical milieu within an organelle has been evolutionarily optimized to enable the biochemistry that occurs within. We study how organelle function impacts cell function by mapping ions within the organelle lumens using a chemical imaging technology based on DNA. DNA self- assembles into molecularly precise, synthetic assemblies, commonly referred to as DNA nanodevices. Our DNA nanodevices are ion responsive, fluorescent probes that can be targeted to specific organelles(1). These reporters can then quantitatively image ions in organelles of cells in culture, in live multicellular organisms (2) as well as in cells obtained from blood draws (3) or skin biopsies from human patients (4). I will focus on a recent finding where we solved a thirty-year problem in molecular sensing by mapping lumenal calcium in acidic organelles and in doing so, identified the first example of a human lysosomal Ca2+ importer.
References:
1. Tinker, J., et. al. Quantitative chemical imaging of organelles. Acc. Chem. Res., 2024, 57, 1906-1917
2.Narayanaswamy, N. et. al. A pH-correctable, DNA-based fluorescent reporter for organellar Calcium. Nat. Methods, 2019, 16, 95-102
3. Cui, C. et al. A lysosome-targeted DNA nanodevice selectively targets macrophages to attenuate tumours. Nat. Nanotechnol., 2021, 16, 1394-1402.
4. Leung, K., et al. A DNA nanomachine chemically resolves lysosomes in live cells. Nat. Nanotechnol., 2019, 14, 176-183.
5. Zajac M., et al. A mechanism of lysosomal calcium entry. Sci. Adv. 2024, 10, eadk2317.