Research Summary

Senior Fellowship research summary

All cells are constantly bombarded by diverse molecular signals. An organism’s or cell’s ability to sense and respond to these molecular signals from its environment is crucial to its survival. Many of these are small, diffusible molecules called second messengers. Cells are thus detecting multiple second messengers at various levels and locations and must therefore be able to instigate a range of responses. Unsurprisingly second messenger signaling pathways in cells are interlinked. Indeed several bacteria and viruses subvert the cell’s signaling machinery to infect the host. Thus understanding second messenger signaling has enormous implications in combating infection. The spatial aspect to the receipt and response of a signal by the cell is thus crucial to achieving this understanding.

Due to its nanoscale dimensions and ability to self-assemble via specific base pairing, DNA is rapidly taking on a new aspect where it is finding use as a construction element for architecture on the nanoscale. By and large, structural DNA nanotechnology has relied on Watson-Crick base pairing to build architectures of exquisite complexity. We have been interested in developing non-Watson-Crick based building blocks to make architecturally simple yet functional DNA-based molecular devices. We have recently created a DNA-based molecular device that functions as an excellent pH sensor and, when interfaced with proteins, is capable of providing spatiotemporal pH maps of their environments with unprecedented sensitivity within endosomes of living cells. We now seek to target this DNA sensor to other cellular locations, such as the cytoplasm, different cellular organelles etc. This would then open up a whole range of applications of DNA as a scaffold to enable second messenger sensing inside living cells.