Semi-synthetic, magneto-photonic circuit for non-invasive control of cellular function - PROJECT SUMMARY/ABSTRACT
Technological advances in molecular biology have led to the development of a variety of innovative tools to
control gene expression. Those tools are crucial for both interrogating complex biological questions and
developing the next generation of therapeutics. Yet, there are two main challenges that remain to be resolved.
One is remote controlling of transcription on demand with the utmost temporal and spatial resolution. The other
is to avoid crosstalk with existing signaling pathways.
In this study, we propose to develop a new genetic tool based on synthetic biology to better control gene
expression within cells. This novel tool is based on rewiring cellular networks and converting energy into
biological action. We intend to harness the power of electromagnetism and biophotonics to control gene
expression. Our goal is to devise multiplex gene arrangements, fusion proteins and transcription factors, that
can be controlled remotely by electromagnetic fields (EMF). This unique, artificial cellular machinery will use
biophotonic principles for activation of specific transcription factors and subsequently switch on gene
transcription with the utmost precision.
In the first Aim we will develop and evolve a genetically encoded biomagnetic switch that can convert EMF to
photons. In parallel, in the second Aim we will develop an orthogonal transcription machinery that interacts with
the biomagnetic switch and controls transcription without interacting with any endogenous signaling pathway.
Finally, in the third Aim we will test the synthetic circuit in vivo, in a relevant animal model.
This magneto-photonic circuit will by-pass the limitations of current chemical, optical, and magnetic approaches
by allowing genetically targeted, non-invasive remote control of gene expression in a highly precise and
physiologically relevant temporal manner. We anticipate that upon completion of the proposed research we will
create an innovative tool that will be immensely beneficial for basic research, drug development and developing
the next generation of synthetic biology-based therapeutics.
