Research & Development World

  • R&D World Home
  • Topics
    • Aerospace
    • Automotive
    • Biotech
    • Careers
    • Chemistry
    • Environment
    • Energy
    • Life Science
    • Material Science
    • R&D Management
    • Physics
  • Technology
    • 3D Printing
    • A.I./Robotics
    • Software
    • Battery Technology
    • Controlled Environments
      • Cleanrooms
      • Graphene
      • Lasers
      • Regulations/Standards
      • Sensors
    • Imaging
    • Nanotechnology
    • Scientific Computing
      • Big Data
      • HPC/Supercomputing
      • Informatics
      • Security
    • Semiconductors
  • R&D Market Pulse
  • R&D 100
    • Call for Nominations: The 2025 R&D 100 Awards
    • R&D 100 Awards Event
    • R&D 100 Submissions
    • Winner Archive
    • Explore the 2024 R&D 100 award winners and finalists
  • Resources
    • Research Reports
    • Digital Issues
    • R&D Index
    • Subscribe
    • Video
    • Webinars
  • Global Funding Forecast
  • Top Labs
  • Advertise
  • SUBSCRIBE

Biophysicists unravel secrets of genetic switch

By R&D Editors | August 31, 2012

GeneticSwitch2-250

Lysis plaques of lambda phage on E. coli bacteria.

When
an invading bacterium or virus starts rummaging through the contents of
a cell nucleus, using proteins like tiny hands to rearrange the host’s
DNA strands, it can alter the host’s biological course. The invading
proteins use specific binding, firmly grabbing onto particular sequences
of DNA, to bend, kink and twist the DNA strands. The invaders also use
non-specific binding to grasp any part of a DNA strand, but these
seemingly random bonds are weak.

Emory
University biophysicists have experimentally demonstrated, for the
first time, how the nonspecific binding of a protein known as the lambda
repressor, or C1 protein, bends DNA and helps it close a loop that
switches off virulence. The researchers also captured the first
measurements of that compaction.

Their
results, published in Physical Review E, support the idea that
nonspecific binding is not so random after all, and plays a critical
role in whether a pathogen remains dormant or turns virulent.

“Our
findings are the first direct and quantitative determination of
non-specific binding and compaction of DNA,” says Laura Finzi, an Emory
professor of biophysics whose lab led the study. “The data are relevant
for the understanding of DNA physiology, and the dynamic characteristics
of an on-off switch for the expression of genes.”

C1
is the repressor protein of the lambda bacteriophage, a virus that
infects the bacterial species E. coli, and a common laboratory model for
the study of gene transcription.

GeneticSwitch3

Transient-loop formation, left, occurs due to non-specific binding of proteins (small orange disks) to DNA (black line). DNA is attached at one end to the glass surface of a microscope flow-chamber and at the other end to a magnetic bead (large gray disk) that reacts to the pulling force of a pair of magnets. The weak, non-specific DNA-protein interactions are disrupted as the force increases. Graphic by Monica Fernandez

The
virus infects E. coli by injecting its DNA into the host cell. The
viral DNA is then incorporated in the bacterium’s chromosome. Shortly
afterwards, binding of the C1 protein to specific sequences on the viral
DNA induces the formation of a loop. As long as the loop is closed, the
virus remains dormant. If the loop opens, however, the machinery of the
bacteria gets hi-jacked: The virus switches off the bacteria’s genes
and switches on its own, turning virulent.

“The
loop basically acts as a molecular switch, and is very stable during
quiescence, yet it is highly sensitive to the external environment,”
Finzi says. “If the bacteria is starved or poisoned, for instance, the
viral DNA receives a signal that it’s time to get off the boat and
spread to a new host, and the loop is opened. We wanted to understand
how this C1-mediated, loop-based mechanism can be so stable during
quiescence, and yet so responsive to switching to virulence when it
receives the signal to do so.”

Finzi
runs one of a handful of physics labs using single-molecule techniques
to study the mechanics of gene expression. In 2009, her lab proved the
formation of the C1 loop. “We then analyzed the kinetics of loop
formation and gained evidence that non-specific binding played a role,”
Finzi says. “We wanted to build on that work by precisely characterizing
that role.”

Emory
undergraduate student Chandler Fountain led the experimental part of
the study. He used magnetic tweezers, which can pull on DNA molecules
labeled with miniscule magnetic beads, to stretch DNA in a microscope
flow chamber. Gradually, the magnets are moved closer to the DNA,
pulling it further, so the length of the DNA extension can be plotted
against the applied force.

“You
get a curve,” Finzi explains. “It’s not linear, because DNA is a
spring. Then you put the same DNA in the presence of C1 protein and see
how the curve changes. Now, you need more force to get to the same
extension because the protein holds onto the DNA and bends it.”

GeneticSwitch4

Specifically-bound proteins are shown as orange ovals on a thicker part of the DNA sequence and non-specifically bound proteins are portrayed as gray ovals on regular DNA. Non-specific, transient loops facilitate the coming together of the specifically-bound proteins that mediate formation of the “switch loop”. Once this loop is formed, non-specifically bound protein further stabilize it by increasing the length of the closure in a zipper-like effect. Graphic by Monica Fernandez

An
analysis of the data suggests that, while the specific binding of the
C1 protein forms the loop, the non-specific binding acts like a kind of
zipper, facilitating the closure of the loop, and keeping it stable
until the signal comes to open it.

“The
zipper-like effect of the weaker binding sites also allows the genetic
switch to be more responsive to the environment, providing small
openings that allow it to breathe, in a sense,” Finzi explains. “So the
loop is never permanently closed.”

The information about how the C1 genetic switch works may provide insights into the workings of other genetic switches.

“Single-molecule
techniques have opened a new era in the mechanics of biological
processes,” Finzi says. “I hope this kind of experiment will lead to
better understanding of how our own DNA is compacted into chromosomes,
and how it unravels locally to become expressed.”

Other
authors on the paper include Sachin Goyal, formerly a post-doc in the
Finzi lab; Emory cell biologist David Dunlap; and Emory theoretical
physicist Fereydoon Family. The research was funded by the National
Institutes of Health.

Stretching DNA to quantify nonspecific protein binding

Source: Emory University

Related Articles Read More >

Floating solar mats clean polluted water — and generate power
New AI model offers faster, adaptive CO₂ retrieval from satellite data
8 major R&D moves this week: Samsung invests record $24B while Porsche cuts 3,900 jobs
Ex-Google AI team launches “Generation,” an AI-driven fragrance venture
rd newsletter
EXPAND YOUR KNOWLEDGE AND STAY CONNECTED
Get the latest info on technologies, trends, and strategies in Research & Development.
RD 25 Power Index

R&D World Digital Issues

Fall 2024 issue

Browse the most current issue of R&D World and back issues in an easy to use high quality format. Clip, share and download with the leading R&D magazine today.

Research & Development World
  • Subscribe to R&D World Magazine
  • Enews Sign Up
  • Contact Us
  • About Us
  • Drug Discovery & Development
  • Pharmaceutical Processing
  • Global Funding Forecast

Copyright © 2025 WTWH Media LLC. All Rights Reserved. The material on this site may not be reproduced, distributed, transmitted, cached or otherwise used, except with the prior written permission of WTWH Media
Privacy Policy | Advertising | About Us

Search R&D World

  • R&D World Home
  • Topics
    • Aerospace
    • Automotive
    • Biotech
    • Careers
    • Chemistry
    • Environment
    • Energy
    • Life Science
    • Material Science
    • R&D Management
    • Physics
  • Technology
    • 3D Printing
    • A.I./Robotics
    • Software
    • Battery Technology
    • Controlled Environments
      • Cleanrooms
      • Graphene
      • Lasers
      • Regulations/Standards
      • Sensors
    • Imaging
    • Nanotechnology
    • Scientific Computing
      • Big Data
      • HPC/Supercomputing
      • Informatics
      • Security
    • Semiconductors
  • R&D Market Pulse
  • R&D 100
    • Call for Nominations: The 2025 R&D 100 Awards
    • R&D 100 Awards Event
    • R&D 100 Submissions
    • Winner Archive
    • Explore the 2024 R&D 100 award winners and finalists
  • Resources
    • Research Reports
    • Digital Issues
    • R&D Index
    • Subscribe
    • Video
    • Webinars
  • Global Funding Forecast
  • Top Labs
  • Advertise
  • SUBSCRIBE