Quantitative Chemical Imaging in Live Cells

Friday, March 6, 2020 -
2:00pm to 3:00pm
The FUNG Auditorium
Yamuna Krishnan

Professor at the Department of Chemistry & Grossman Institute for Neuroscience

University of Chicago 

Quantitative Chemical Imaging in Live Cells

Abstract: 

The chemical milieu within an organelle has been evolutionarily optimized to enable the biochemistry that occurs within. My lab studies how organelle function impacts cell function by mapping chemicals within the organelle lumens using a new, quantitative chemical imaging technology based on DNA. DNA self-assembles into molecularly precise, synthetic assemblies, commonly referred to as DNA nanodevices. My lab creates DNA nanodevices that are chemically responsive, fluorescent probes that can be targeted to specific organelles(1). I will discuss how we get these probes to interface with cells in programmable and targeted ways to localize in specific organelles. I will show how we use these reporters to quantitatively image chemical messengers 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 two recent findings. One, 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 lysosomal Ca2+ importer in the animal kingdom (2). In the second, I will describe a DNA-based voltmeter using which, we have measured the membrane potentials of several organelles in situ in live cells, many of which were unknown till now (5).

References:

1.     Chakraborty, K., et. al. Nucleic acid based nanodevices in biological imaging. Ann. Rev. Biochem, 2016, 85, 349-373.

2.     Narayanaswamy, N. et. al. A pH-correctable, DNA-based fluorescent reporter for organellar Calcium. Nature Methods, 2019, 16, 95-102.

3.     Thekkan, S. et al. A DNA-based fluorescent reporter maps HOCl production in the maturing phagosome. Nature. Chem. Biol. 2019, in press.

4.     Leung, K., et al. A DNA nanomachine chemically resolves lysosomes in live cells. Nature Nanotechnology, 2019, in press.

5.     Saminathan A., et al. A DNA-based voltmeter for organelles. bioRxiv 523019.

Bio: 

Yamuna Krishnan is Professor at the Department of Chemistry at the University of Chicago since 2014. She received a PhD in Organic Chemistry in 2002 from the Indian Institute of Science, Bangalore and was an 1851 Research Fellow at the University of Cambridge, UK. Her research group pioneered the use of DNA-nanotechnology to study living cells and taking DNA-nanotechnology into the world of precision medicine. Selected honors include the Infosys Prize for Physical Sciences in 2017, the Shanti Swarup Bhatnagar Award, the Innovative Young Biotechnologist Award, the INSA Young Scientist Medal, the Wellcome-Trust DBT Senior Research Fellowship and the YIM Boston Young Scientist Award. She was featured on Cell’s top 40 under 40 of scientists that are shaping current and future trends in Biology and the LSDP’s Top 100.