| RESEARCH HIGHLIGHTS |
their individual application. The triple-killing mechanism of these ternary combinations, and the potential to rotate the three combinations during therapy, makes it much harder for microbes to develop resistance to them. Using other antibiotics in combination with colistin has the added advantage that it reduces the amount of colistin needed and the toxicity to the patient.
The antibiotics are easy to self-administer.
“Our formulations are designed to be delivered into the deep-lung region by a portable, easy- to-use dry-powder inhaler, which is faster, more direct and more convenient than other modes of treatment,” says Heng. The team intends to conduct in vivo studies in animals and then humans in
collaboration with hospital clinicians. The researchers note that the same strategy could be applied to fight other drug-resistant bacteria.
1. Lee, S. H., Teo, J., Heng, D., Ng, W. K., Zhao, Y. & Tan, R. B. H. Tailored antibiotic combination powders for inhaled rotational antibiotic therapy. Journal of Pharmaceutical Sciences 105, 1501–1512 (2016).
Neuroscience
DROPPING LIKE FLIES
LIGHT-SENSITIVE MOLECULE SILENCES NEURAL CIRCUITS FOR BRAIN RESEARCH
A*STAR researchers have made genetically modified flies that drop mid-flight when struck by light1. The optogenetic trick gives scientists an important new way to study the brain’s workings. The brain is abuzz with activity. Electrical
signals carried by ions move along busy neuronal circuits to enable activities as simple as breathing and as complex as recalling memories. When these circuits do not behave correctly, they can result in brain disorders like major depression. This is why researchers need flexible tools to see what happens when certain neurons are activated or suppressed. One such tool is optogenetics, which uses
light to control genetically modified cells. While a popular approach for studying what happens when certain neurons are excited or activated, optogenetic techniques for investi- gating neuronal inhibition — the silencing of brain activity — are more limited. To solve this puzzle, Adam Claridge-Chang from the A*STAR Institute of Molecular and
www.astar-research.com
Flies carrying the light-sensitive anion channelrhodopsin neuronal inhibitor in their sweet-tasting cells can’t resist licking sugar water under red light, but exposure to green or blue light blocks their normal drinking behavior.
Cell Biology looked into light-sensitive proteins called anion channelrhodopsins (ACRs) previously isolated from an algae. ACRs act like a gate: when illuminated by
a specific wavelength of light they let more neg- atively charged ions into the neurons. In 2015, this physiological activity had been shown to inhibit brain-cell activity in a Petri dish. So the team decided to test these proteins in a living animal — the vinegar fly, Drosophila, an important model for biomedical research. Choosing the right behavioral tests to vali-
date the ACRs, however, was not trivial. “With an activator, you have a wide range of choices, because when you activate those cells the animal should do something,” says Claridge-Chang. “It’s a bit harder when you’re trying to remove a function — you have to prove that the animal stopped doing something.” Movement was the obvious choice. When
flies carrying the ACR genes were illuminated with specific wavelengths while crawling on a vertical wall, they almost immediately dropped
to the ground, lying motionless. “The paralysis happens extremely fast, within tens of millisec- onds,” explains Claridge-Chang. Another test focused on the flies’ sweet
tooth. Flies typically cannot resist sugar, and so the team targeted taste receptors and sup- pressed their ability to detect sweetness. When illuminated, the flies did not lick sugar droplets placed in front of their mouths (see image). The team released their findings prior to
publication, and it exploded on social media within the Drosophila community. Since then, more than a dozen labs have started using the lab’s ACR flies to independently validate the team’s findings and analyze brain function. Moving forward, Claridge-Chang’s team
will use the flies to investigate how emotional behaviors are affected in disorders like anxiety and depression.
1. Mohammed, F., Stewart, J. C., Ott, S., Chlebikov, K., Chua, J. Y. et al. Optogenetic inhibition of behavior with anion channelrhodopsins. Nature Methods 14, 271–274 (2017).
A*STAR RESEARCH 47
© 2017 Katarina Chlebikova
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