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Research Highlights

Geometric Viability Assay: Speeding up antibiotic discovery research

[video:https://www.youtube.com/watch?v=9tAIbpZ_uOw]

 

Using "Quantum-dot" based antibiotics to clear infection in mice

"Photoactivated antibiotics to treat intracellular infection of bacteria" on the use of Quatum dot based antibiotics to reduce intracellular infections in a bone-infection model.

Infrared-light activated Quatum dots kill MDR bacterial infection in a mouse model. The study shows that QD antibiotics are safe and effective in an abcess infection model.

Using "Quantum-dot" based antibiotics to clear biofilms in synergy with traditional antibiotics

Quantum dot antibiotics can treat biofilms of multi-drug resistant bacterial isolates of MRSA, Psuedomonas aeruginosa, and Escherichia coli.

Quantum dot antibiotic animal safety and efficacy study "Photoexcited quantum dots as efficacious and nontoxic antibiotics in an animal model" shows that specifically-engineered and light-activated Quantum dot antibiotics can treat infection of MDR bacteria in an in vivo model, and are safe and non-toxic. 

Near-infrared-active quantum dots (QDs) have been designed to generate therapeutic superoxide radicals within pathogens. The combination of activation using a deep-tissue-penetrating light source, and selective mechanism of action, produces an effective treatment.

Facile and Accelerated Specific Thaerpeutic (FAST) platform is used to develop antisense molecules that target genes of interest in non-model or genetically intractable spcies, such as MDR clinical isolates of bacteria. This allows us to identify which genes are important for antibtioic tolerance and/or resistance. This process can identify new gene targets in MDR bacteria in less than 5 days. 

Transcriptomic Response to Superoxide Generating Quantum Dots in Echerichia coli confirms mechanism of action of Quatum dot antibiotics. We identify genes demonstrate a consistent association with the DNA damage response and deactivation of iron–sulfur clusters.

Potentiating antibiotic efficacy via perturbation of non-essential gene expression shows that combining individually fitness-neutral perturbations can compound fitness impacts and sesitize bacteria to antibiotics.

CHAOS Therapy

We report novel CHAOS Therapy to Slow down bacterial evolution of antibiotic resistance in paper "Multiplexed deactivated CRISPR-Cas9 gene expression perturbations deter bacterial adaptation by inducing negative epistasis" published in Nature Communications Biology.

See media coverage

Superbug

We report using Quantum dot antibiotics to potentiate antibiotics in highly drug-resistant clinical isolates in paper "Potentiating clinical drug resistant bacteria via stimuli-activated superoxide generation" published in Science Advances.

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A lot of E. Coli petri dishes

We report a novel Light-Activated Nanotherapy that kills Clinically isolated Multi Drug Resistant Bacteria in manuscript led by Colleen and Sam, "Photoexcited Quantum Dots for Killing Multi-Drug Resistant Bacteria" in Nature Materials!

PO-biofuels

We report a CRISPR gene expression perturbation approach to increase bacterial tolerance to biofuels "CRISPR gene expression perturbations for enhancing bacterial tolerance to biofuels" in Frontiers in Bioengineering and Biotechnology!

TA-HCV

We report a new mathematical model fitted to experimental data for predicting intracellular HCV dynamics, "Intracellular hepatitis C modeling predicts infection dynamics and viral protein mechanisms" in Journal of Virology!

TA space

We report transcriptomic signature of E. coli adapted to antibiotics on the International Space Station, in "Spaceflight modifies Escherichia coli gene expression in response to antibiotic exposure and reveals role of oxidative stress." Frontiers of Microbiology!

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Tolerome

We report the first database that can mine gene expression data sets to identify key players of adaptive resistance in bacteria. "The Tolerome: A database of transcriptome-level contributions to diverse Escherichia coli resistance and tolerance phenotypes." published in ACS Synthetic Biology.

Link to database

Diagrams on the experiment

We are pleased to report a new systems bology approach to mine and identify key gene signatures in complex gene expression data sets in our publication "Transcriptome level signatures in gene expression and gene expression variability during bacterial adaptive evolution," in mSphere.

Molecules and graphs

We are pleased to report four publications on novel single-molecule sequencing methods in 2017! These publications can be found in ACS Nano, JACS, and Small.

Description of an experiment along with pictures and diagrams of test tubes

We present a novel application of CRISPR-Cas9 technology for investigating how gene expression governs the adaptive pathways available to bacteria during the evolution of resistance in Peter's paper titled, "CRISPR perturbation of gene expression alters bacterial fitness under stress and reveals underlying epistatic constraints" in ACS Synthetic biology!

We report a novel tool for synthetic biology and metabolic engineering by investigating transcriptional interference mechanisms of antisense roadblock and RNA polymerase traffic in a set of convergent promoters, in paper led by Toni, "Transcriptional Interference in convergent promoters as a means for Tunable Gene Expression" in ACS Synthetic biology!

 

Description of how the antibiotic works

We report a novel gene expression variability based approach to identify important genes involved in bacterial adaptive resistance, in paper led by Keesha, "Gene expression variability underlies adaptive resistance in phenotypically heterogenous bacterial populations" in ACS Infectious Diseases!

Antisense Transcription

We report a new mathematical model that describes tunabilty of genetic switch behavior during antisense transcription, in a paper led by Toni, "cis-Antisense Transcription Gives Rise to a Tunable Genetic Switch Behavior: A Mathematical Modeling Approach" in PLoS ONE!

Some cell/molecule diagram in detail

We report a bet-hedging based mechanism of adaptive resistance to PNA based antimicrobials in a paper led by Colleen, "Sequence-specific peptide nucleic acid based antisense inhibitors of TEM-1 beta-lactamase and mechanism of adaptive resistance" in ACS Infectious Diseases!

CGTA

We reveal novel nanoelectronic fingerprints for DNA in paper led by Josep, "Measurements of Single nucleotide Electronic states as Nanoelectronic fingerprints for Identification of DNA Nucleobases, their Protonated and Unprotonated states, Isomers and Tautomers," in Journal of Physical Chemistry Letters B!

Constrictor molecule

New Metabolic Flux Analysis tool CONSTRICTOR is available on Opensource

Our lab designs and reports a new FBA tool called CONSTRICTOR, in a paper led by Keesha, "CONSTRICTOR: Constraint modification provides insight into design of biochemical networks" in PLoS ONE!

Sam's paper "Multiple Energy Exciton shelves in Quantum Dot-DNA Nano-bioelectronics" is published in The Journal of Physical Chemistry Letters!

Our mathematical modeling paper on "A pharmacokinetic/viral kinetic model to evaluate treatment of chronic hepatitis C virus with danoprevir" accepted in Antiviral Therapy!

Anushree's paper on "Antagonistic self-sensing and mate-sensing signaling controls antibiotic-resistance transfer" is published in PNAS!

Lab web 2

Welcome

Our research group uses a combination of interdisciplinary approaches including synthetic biology, systems biology, microbiology, synthetic chemistry, and nanoengineering to address the key global challenge involving antimicrobial resistance. We aim at developing strategies for rationally engineering next-generation smart antimicrobials that can eliminate multi-drug resistant superbugs, with the ultimate goal of creating therapies that can evade evolution of drug-resistance in microbes. To this end, we are also interested in investigating the non-genetic mechanisms responsible for antimicrobial tolerance/resistance to devise strategies that can one day prevent evolution of drug resistance. Using synthetic biology tools we are also interested in designing, constructing and engineering modular synthetic genetic devices based on less-explored naturally occurring mechanisms, for both understanding fundamentally how nature works as well as built devices for potential biotechnological applications.

Featured by CU Engineering

[video:https://youtu.be/VcXuTGNphPY]

 

Scientists are using chaos to try and beat E. coli

--by Chase Purdy, Quartz

For years, scientists at the University of Colorado have sought to defuse the destructive powers of a pernicious bacteria that often sneaks into the human body through tainted food. Turns out, one of the most effective ways to beat E. coli is to sow chaos. (Read more)

Lab invents CHAOS Therapy to Slow down the bacterial evolution of antibiotic resistance

CHAOS Therapy

How to stop an antibiotic-resistant superbug

-- By Trent Knoss, University of Colorado press release

A genetic disruption strategy developed by University of Colorado Boulder researchers effectively stymies the evolution of antibiotic-resistant bacteria such as E. coli, giving scientists a crucial leg up in the ongoing battle against deadly superbugs. (Read more)

Research led by CU Boulder could block E.coli, other superbugs

-by CHARLIE BRENNAN, Denver Post and Boulder Daily Camera

Kryptonite for superbugs could be on the horizon, as a result of research led by University of Colorado researchers that hinders the progress of antibiotic-resistant superbugs such as E.coli... (Read more)

Anushree speaks at the Institute of Systems Biology's Future of Health Symposium

[video:https://youtu.be/wB5Q9gqMMcw]

Session 3: Prevention and Therapy Anushree Chatterjee, PhD | University of Colorado at Boulder "From Synthetic Biology to Nanobiotechnology: Rational Antimicrobial Engineering Approaches for Combating Multidrug-Resistant Pathogens"

BBC features our Quantum dot antibiotic research!

Lots of medicine

CGTN America features our lab's research

[video:https://youtu.be/VSE2RRv4JEc]

 

Battling Bacteria: Back to Square 1?

--Lab Research Featured by Hamodia

A WATERSHED IN RESEARCH STUDIES

Trailblazing research studies of diverse approaches, recently published in peer-reviewed science journals, are poised to combat antibiotic resistance. Hamodia interviewed these leading researchers, each at the helm of his study. Assistant Professors Prashant Nagpal and Anushree Chatterjee of the Department of Chemical and Biological Engineering in the University of Colorado Boulder, whose studies were published in the science journals Nature Materials and Science Advances. “Our approach is a two-pronged strategy to fight antibiotic-drug resistance..... (Read more)

MSN, Newsweek, Science News, CIDRAP features our work on potentiating drug-resistant clinical bacteria to antibiotics

[video:https://youtu.be/qBCrZCmgZos]

Boulder, Colorado —Light-activated nanoparticles, also known as quantum dots, can provide a crucial boost in effectiveness for antibiotic treatments used to combat drug-resistant superbugs such as E. coli and Salmonella, new CU Boulder research shows......

UC Health features our research on combating antibiotic resistance

Todd Neff for UC Health- DENVER, CO. Science can border on science fiction. Designing swarms of infinitesimal semiconductors that, shined with green light, turn standard oxygen into a superoxide that makes life hell for drug-resistant bacteria – that qualifies.....

Voice of America features our Quantum dot based Antibiotic research

[video:https://youtu.be/6xGn-z6B_uM]

Boulder, Colorado — Scientists have been creating antibiotics to kill deadly bacteria for nearly 80 years. Unfortunately, the bacteria that cause disease can adapt so quickly, some have evolved into superbugs that are resistant to all antibiotics, and making new drugs is a long, expensive, involved process....

ABC Channel News Features our Light-activated nanotherapy against antibiotic-resistant “superbugs”!

ABC News

[video: https://www.thedenverchannel.com/news/local-news/cu-researchers-use-light-activated-nanoparticles-used-to-kill-antibiotic-resistant-superbugs]

In the ever-escalating evolutionary battle with drug-resistant bacteria, humans may soon have a leg up thanks to adaptive, light-activated nanotherapy developed by researchers at the University of Colorado Boulder.

Antibiotic-resistant bacteria such as Salmonella, E. Coli and Staphylococcus infect some 2 million people and kill at least 23,000 people in the United States each year. Efforts to thwart these so-called “superbugs” have consistently fallen short due to the bacteria’s ability to rapidly adapt and develop immunity to common antibiotics such as penicillin.  

New research from CU-Boulder, however, suggests that the solution to this big global problem might be to think small—very small.

In findings published today in the journal Nature Materials, researchers at the Department of Chemical and Biological Engineering and the BioFrontiers Institute describe new light-activated therapeutic nanoparticles known as “quantum dots.” The dots, which are about 20,000 times smaller than a human hair and resemble the tiny semiconductors used in consumer electronics, successfully killed 92 percent of drug-resistant bacterial cells in a lab-grown culture.....

News