A DNA nanomachine that maps spatial and temporal pH changes inside living cells, Nature Nanotechnology, 2009, 4(5),325-330.

DNA nanomachines are synthetic assemblies that switch between defined molecular conformations upon stimulation by external triggers. 

An autonomous DNA nanomachine maps spatiotemporal pH changes in a multicellular living organism, Nature Communications, 2011, 2:340.

DNA nanomachines are artifi cially designed assemblies that switch between defi ned conformations in response to an external cue.

Two DNA nanomachines map pH changes along intersecting endocytic pathways inside the same cell, Nature Nanotechnology, 2013, 8, 459-467.

DNA is a versatile scaffold for molecular sensing in living cells, and various cellular applications of DNA nanodevices have been demonstrated. 

A pH-independent DNA nanodevice for quantifying chloride transport in organelles of living cells. Nat Nanotechnol, 2015, 10, 645-651.

The concentration of chloride ions in the cytoplasm and subcellular organelles of living cells spans a wide range (5–130 mM), and is tightly regulated by intracellular chloride channels or transporters

High lumenal chloride in the lysosome is critical for lysosome function, eLife, 2017, 6:e28862.

Lysosomes are organelles responsible for the breakdown and recycling of cellular machinery.

Visualization of Calcium Ion Loss from Rotavirus during Cell Entry, Journal of Virology, 2018, 92(24), e01327-18.

Bound calcium ions stabilize many nonenveloped virions. Loss of Ca2 from these particles appears to be a regulated part of entry or uncoating.

A DNA nanomachine chemically resolves lysosomes in live cells, Nature Nanotechnology, 2019, 14, 176-183.

Lysosomes are multifunctional, subcellular organelles with roles in plasma membrane repair, autophagy, pathogen degradation and nutrient sensing. 

DNA nanodevices map enzymatic activity in organelles, Nature Nanotechnology, 2019, 14, 252-259.

Cellular reporters of enzyme activity are based on either fluorescent proteins or small molecules. 

A pH-correctable, DNA-based fluorescent reporter for organellar calcium, Nature Methods, 2019, 16, 95-102.

It is extremely challenging to quantitate lumenal Ca2+ in acidic Ca2+ stores of the cell because all Ca2+ indicators are pH sensitive, and Ca2+ transport is coupled to pH in acidic organelles. 

A DNA-based fluorescent reporter maps HOCl production in the maturing phagosome, Nature Chemical Biology, 2019, 15(12), 1165-1172.

Phagocytes destroy pathogens by trapping them in a transient organelle called the phagosome where they are bombarded with reactive oxygen (ROS) and reactive nitrogen species (RNS).

A DNA-based fluorescent probe maps NOS3 activity with sub-cellular spatial resolution, Nature Chemical Biology, 2020, 16, 660-666.

The newfound ability to spatially map NOS3 activity provides a platform to discover selective regulators of the distinct pools of NOS3.

DNA-based fluorescent probes of NOS2 activity in live brains, Proc. Natl. Acad. Sci. U.S.A. 2020, 117 (26) 14694-14702.

By mapping phagosomal NO produced in microglia of live zebrafish brains, we found that single-stranded RNA of bacterial origin acts as a PAMP and activates NOS2 by engaging TLR-7.

Tubular lysosomes harbor active ion gradients and poise macrophages for phagocytosis, Proc. Natl. Acad. Sci. U. S. A., 2021, 118 (41) e2113174118.

Tubular lysosomes are studied either by inducing autophagy or by activating immune cells, both of which lead to cell states where lysosomal gene expression differs from the resting state.

Organelle-level precision with next-generation targeting technologies, Nature Reviews Materials (2021)

Intracellular organelles are subsystems within a cell, whose activity and chemical composition reflect the metabolic state of live cells.

Tissue-specific targeting of DNA nanodevices in a multicellular living organism, eLife, 2021,10:e67830.

The amenability of DNA nanostructures to tissue-specific targeting in vivo significantly expands their utility in biomedical applications and discovery biology.

A DNA-based voltmeter for organelles, Nature Nanotechnology, 2021, 16, 96-103.

Voltair can potentially guide the rational design of biocompatible electronics and enhance our understanding of how membrane potential regulates organelle biology.


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