Recording of cellular physiological histories along optically readable self-assembling protein chains.

Area of Science:

• Molecular Biology
• Cellular Biology
• Neuroscience

Background:

• Understanding cellular physiological histories is crucial for deciphering normal biological processes and disease mechanisms.
• Current methods for observing cellular histories often lack the resolution or throughput required for comprehensive analysis.

Purpose of the Study:

• To develop a novel, fully genetically encoded system for continual digital recording of biological information within cells.
• To enable high-throughput readout of cellular physiological histories in fixed cells using conventional microscopy.

Main Methods:

• Expression recording islands (ERIs) were engineered using self-assembling protein subunits.
• Each subunit carries unique epitope tags corresponding to specific cellular states or functions (e.g., gene expression).
• Information is stored in growing intracellular protein chains, allowing temporal readout along the chain.

Main Results:

• The ERI system successfully recorded gene expression timecourses in response to pharmacological and physiological stimuli.
• Recordings were achieved in cultured neurons and in vivo within living mouse brains.
• The method demonstrated a time resolution of less than a day over periods spanning days to weeks.

Conclusions:

• Expression recording islands provide a powerful new tool for digital, high-throughput recording of cellular histories.
• This technology facilitates detailed analysis of dynamic cellular processes, including gene expression changes over extended periods.
• The findings have significant implications for understanding cellular dynamics in both normal physiology and disease states.