Publications:
¹Real-time light-driven
temporal control of gene expression and protein concentration in S.
cerevisiae. Justin Melendez, Benjamin Oakes, Marcus Noyes, Megan N.
McClean. Lewis-Sigler Institute, Princeton University, Princeton, NJ., 2012
Yeast Genetics and Molecular Biology Meeting, August 3,
2012
Background
Biological
signaling networks, like electrical circuits, take specific inputs and convert
them into appropriate outputs.
Electrical engineers uncover the inner workings of such circuits by
measuring the transfer function between a specific input voltage signal and
output voltage. This transfer
function indicates how the electrical signal propagates through the network and
allows the engineer to formulate and refine a model of the network. Electrical input signals are created
using an electronic device called a signal generator. These devices are capable of creating
arbitrary voltage waveforms such as sines, ramps, and pulses. Additionally, signal generators can be
used to control electrical circuits to produce desired outputs.
Unlike electrical engineers, biologists are very limited in the
input signals they can generate to interrogate and control biological
networks. Typical experiments
perturb the network with a sudden step increase in ligand and assay downstream
gene expression. Such ¿step-shock¿
inputs stimulate the biological network at the receptor level, leaving many
unprobed signaling steps between input and output. When measurement or biological noise is
present, step-shocks have been theoretically shown to be inferior to
time-varying inputs, such as oscillations, for identifying network
components. Overexpression of a
protein of interest is often used to perturb or control a specific biological
pathway, however, the inability to dynamically control the protein concentration
limits the ability to adjust and control the pathway throughout
time.
Biologists are in need of a "signal generator" that can create
time-varying input at multiple points in a biological network. In addition to providing a device for
interrogating biological networks, a biological signal generator would allow for
control of natural and synthetic biological networks used in biomedical and
industrial applications.
The "Smart Stat" uses light-based induction and real-time feedback
control to produce waveforms of gene expression and protein concentration in
continuous or batch cell cultures.
Light as an
induction system has many advantages over chemical induction systems widely used
in industry drug production today. Light induction is inexpensive costing
considerably less than many chemical induction signals. Light as an induction
system can be added or removed instantaneously from a large bioreactor system
while chemical systems require complicated media changes or long periods for the
chemical systems to dilute out. Light intensity can be adjusted to increase,
decrease or change the rate of induction. In conjunction with the automated
sampling system and analysis system described above, light is used to maintain
protein concentration at specific levels or vary protein concentration over
time. Thus, the ¿Smart Stat¿
operates like a biological signal generator for interrogating and controlling
biological networks.
Intellectual Property
status
Patent protection is pending.
Commercialization
Strategy
Princeton University¿s Office of
Technology Licensing is looking to identify appropriate commercial partners for
the further development and commercialization of this technology.
Contact:
Laurie
Tzodikov
Princeton
University Office of Technology Licensing (609) 258-7256
tzodikov@princeton.edu
Princeton
docket # 13-2838