‘Clicked’ Sensors for Visualizing Bio-Analytes in Action

Prof. Ankona Datta
Department of Chemical Sciences
Tata Institute of Fundamental Research
Mumbai, India

ankona@tifr.res.in

https://www.tifr.res.in/~ankona/

Please note that Ankona will give a presentation of her research center (TIFR) and on the Indian research system on April 24th (announced here).

Small molecules and ions are key players in biological regulation and signaling processes. Dynamic changes in distributions of these bio-analytes are functionally relevant and hence essential for driving life. Chemical sensors that can track small molecules and ions in living systems help us record ‘molecular motion pictures’ revealing mechanistic insights into essential life processes and pathophysiological conditions. The challenge lies in developing molecular sensors that can non-invasively report on locations of bio-analytes, their temporal distribution fluctuations, and importantly provide quantification of these fluctuations within living systems. Key to the design of molecular sensors which consist of a receptor unit and a reporter unit, are considerations of selectivity, sensitivity, and importantly reversible response to track changes in molecular distribution. Importantly, sensor design needs to incorporate modular synthetic strategies to allow routes for rapid design variations based on the functional/biological context. For example, ease of changing the reporter unit, receptor unit, or cellular targeting unit in the sensor depending on the identity of the bio-analyte to be detected and its biological address or location.1-5

Toward this aim we have leveraged modular synthetic strategies like “Click” chemistry to develop chemical sensors for live tracking and quantification of bio-analytes. In this talk I will highlight our research in design, development, and applications of fluorescent sensors for tracking proton and metal ion levels in living cells.4,5 Finally, I will touch upon our recent efforts in applying these concepts to design Raman-responsive probes for multiplexed imaging

References

1. Kahali, S.; Baisya, R.; Das, S.; Datta, A., Simultaneous Live Mapping of pH and Hydrogen Peroxide Fluctuations in Autophagic Vesicles. JACS Au 2025.

2. Kundu, R.; Mondal, S.; Kapadia, A.; Banerjee, A. A.; Kucherak, O. A.; Klymchenko, A. S.; Koushika, S. P.; Venkatramani, R.; Vaidya, V. A.; Datta, A., A Cell-Permeable Fluorescent Probe Reveals Temporally Diverse PI(4,5)P2 Dynamics Evoked by Distinct GPCR Agonists in Neurons. bioRxiv 2024, 2024.06.17.599302.

3. Kundu, R.; Kumar, S.; Chandra, A.; Datta, A., Cell-Permeable Fluorescent Sensors Enable Rapid Live Cell Visualization of Plasma Membrane and Nuclear PIP3 Pools. JACS Au 2024, 4 (3), 1004-1017.

4. Kumar Das, S.; Kahali, S.; Kar, S.; Madhavan, N.; Datta, A., Naphthalimide-Based, Single-Chromophore, Emission Ratiometric Fluorescent Sensor for Tracking Intracellular pH. ChemBioChem 2024, 25 (21), e202400538.

5. Kahali, S.; Das, S. K.; Kumar, R.; Gupta, K.; Kundu, R.; Bhattacharya, B.; Nath, A.; Venkatramani, R.; Datta, A., A water-soluble, cell-permeable Mn(II) sensor enables visualization of manganese dynamics in live mammalian cells. Chemical Science 2024, 15 (28), 10753-10769.

Ankona Datta received her B.Sc. and M.Sc. degrees in chemistry from the Indian Institute of Technology, Kharagpur in 2000. She did her Ph.D. on chiral water-soluble porphyrins for catalysis and molecular recognition with Prof. John T. Groves at Princeton University (2006). After graduating from Princeton, she joined as a postdoctoral scholar in the laboratory of Prof. Ken Raymond at the University of California, Berkeley, where she worked on macromolecular MRI contrast agents. Since 2010 she is a faculty member in the Department of Chemical Sciences at the Tata Institute of Fundamental Research, India. Her current research interests are in the fields of Chemical Biology and Molecular Imaging.