Title: Intracellular Electrophysiology
Abstract: I have been interested in exploring how the ionic milieu within an organelle facilitates its lumenal biochemistry and thereby, organelle function. To map these lumenal chemistries, my lab developed a DNA-based, fluorescent reporter technology to quantitatively map ions such as H+, Cl- and Ca2+ within organelles (1). We can now interrogate organelles of cells in culture, in live organisms (2) and in human patient cells (3,4). Our most recent reporter for absolute membrane potential ended a previous misconception by showing that many organelles do in fact, have membrane potential (4). Today I will discuss two new reporters for organellar Na+ and K+ : the final pieces needed to build an electrochemical model for organelle membranes (5,6). The only existing electrochemical model of a biological membrane is that of the neuronal cell membrane, first developed by Hodgkin and Huxley in 1952 (7). To accomplish this for organelles we will need input from physicists, cell biologists and electrophysiologists.
References:
1. Krishnan, Y. et. al. “Quantitative imaging of biochemistry in situ and at the nanoscale.” ACS Cent. Sci., 2020, 6, 1938–1954.
2. Narayanaswamy, N. et. al. “A pH-correctable, DNA-based fluorescent reporter for organellar Calcium.” Nature Methods, 2019, 16, 95-102.
3. Leung, K., et. al. “A DNA Nanomachine chemically resolves lysosomes in live cells.” Nature Nanotechnology, 2019, 14, 176-183.
4. Saminathan, A., et. al. “A DNA-based voltmeter for organelles.” Nature Nanotechnology, 2021, 16, 96-103.
5. Anees, P. et al. “DNA nanodevices measure the organelle-specific activity of potassium channels.” Nature Biotechnology 2023, in press.
6. Zou, J. et al. “A DNA nanodevice maps sodium at single organelle resolution” Nature Biotechnology 2023, in press.
7. Hodgkin A.L., Huxley A.F. “A quantitative description of membrane current and its application to conduction and excitation in nerve”. J. Physiol. 1952, 117, 500–44.
Bio: Prof. Yamuna Krishnan is a professor at the Department of Chemistry, University of Chicago, since August 2014. She has pioneered the interface between DNA nanotechnology and cell biology. Her lab has developed a versatile chemical imaging technology to quantitatively image second messengers in real time, in living cells and genetic model organisms. While her lab is engaged in basic biology – discovering new organellar channels and transporters – she has co-founded two companies –Esya Inc & Macrologic Inc, that utilize her organelle-targeting technology for diagnostics and therapeutics respectively. She is a recipient of the NIH Director’s Pioneer Award, the Ono Pharma Breakthrough Science Award, the Infosys Prize for Physical Sciences, Shanti Swarup Bhatnagar Prize in the Chemical Sciences and the Sun Pharma Foundation Award for Basic Medical Research.
Host: Prof. Jeff Martell
