Overview
Title: Programming DNA to Encode Molecular Organization in Tissues
Abstract:
Massive improvements in DNA sequencing capacity over the past two decades have forced the field of molecular biology to continually reassess the role DNA itself ought to play in biological measurement. DNA and RNA are, on the one hand, biological machinery and, on the other, a vital laboratory medium for amplifying signal. We discuss one particularly powerful instance of these two roles coming together, showing how DNA can be engineered to encode large physical networks of molecules in biological tissue. Samples are first seeded with random, unique DNA sequences. A chemical reaction then pairs each sequence with its neighbors, so that the sequences self-assemble into a vast intermolecular network that encodes the geometry of the sample around it. A sufficiently dense map of these contacts allows relative positions to be reconstructed. We demonstrate this in whole zebrafish embryos and show that unsupervised likelihood maximization decodes the three-dimensional geometry of more than 1e7 molecules in individual specimens, down to length scales of 1-2 microns. Turning to the general problem of decoding geometry from this class of molecular networks, we close by surveying open problems at the interface between the engineering and the theory of reconstruction.
About the NITMB Seminar Series:
The NSF-Simons National Institute for Theory and Mathematics in Biology Seminar Series brings together a mix of mathematicians and biologists to foster discussion and collaboration between the two fields. The seminar series typically takes place on Fridays from 10am – 11am at NITMB. Talks are in-person with the ability to join remotely. Learn more at https://www.nitmb.org/nitmb-seminar-series
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