A Molecular Chart Recorder

Type of Award: Catalyst
Date Awarded: January 2012
Award End Date: December 2013
Amount Awarded: $ 200,000.00
PI(s): Konrad Kording, PhD, NU; Keith Tyo, PhD, NU; Douglas Bishop, PhD, UChicago; Lucia Rothman-Denes,, UChicago;

Abstract: The interplay between millions of neurons allows us to perceive our environment and choose successful actions. Brain scientists, in an attempt to understand this interplay, need to record from progressively more neurons. Neuroscience relies on new developments in recording technology and thus far this progress is largely driven by physics -- thin wires and optical sensors are used to read out signals. We propose to shrink the size of a recording setup by orders of magnitude to produce a molecular tape recorder - that writes time-varying neural activities onto individual DNA molecules.

We will design a system so that it essentially copies just one long DNA molecule (template) during a neuroscience experiment. Some DNA polymerases (DNAP) are capable of copying roughly 1 base pair every millisecond. The position of a base-pair along this molecule thus corresponds to the time it was copied (our "chart"). We will engineer the DNAP so that it makes copying mistakes whenever Ca2+ is high (our "recorder"). If neurons are active, intracellular calcium concentrations increase. Consequently base pairs copied while Ca2+ concentrations were high will have many copying mistakes. Comparing with the template we can thus read out a chart of intracellular Ca2+ concentration. After the experiment, the animal will be killed, the brain will be cut into small pieces and the DNA in neurons will be sequenced and converted into a Calcium chart (our "read out"). This resulting calcium chart characterizes neural activities as a function of time.