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A new optogenetics system can stimulate neurons in an entire population of moving worms simultaneously, exquisitely controlling when they dash forward, back up, or turn around.
The "optogenetic illumination system" delivers light to specific regions on each worm's body, such as its head or tail, and can even be programmed to deliver pulses of light in response to a worm’s behavior.
The study, by Liu et al., appeared in PLOS Biology in January.
At a basic level, optogenetics works like this: Neurons are engineered to express channelrhodopsins, or opsins, that dot the cell’s extremities. These proteins morph their shape when struck by light, forming pores that usher sodium ions into the cell to trigger an action potential. In fruit flies and worms, optogenetics has already been used to study the neural circuits underlying chemotaxis, olfaction, learning, memory and movements.
Worms were engineered to express an optogenetic protein, called "Chrimson," in just six of their neurons. About 40 worms were placed in a small petri dish. A projector, overhead, split red light (630 nm) and cast it, like Broadway spotlights, down on the worms. A camera, placed beneath the petri dish, tracked each worm's movement in real-time and fed that data to the computer. The projector moved around the light, stimulating neurons in each worm's head or butt as desired.
A few things. The computer vision software, which tracks both the 'pose' and behavior of each animal, was custom-made. The hardware setup is fast and flexible. It can deliver pulses of light 25-fold faster than a prior method and, in the future, it could deliver red and blue light simultaneously, the researchers say, "to independently activate 2 different opsins such as the excitatory red opsin Chrimson and the inhibitory blue opsin gtACR2."
C. elegans is a useful model to study the link between neurons and motor coordination because they have exactly 959 somatic cells, 302 of which make up the ganglia, or primitive brains, within their head and tail. The lineage of each cell has been mapped, which means we know where it came from and, in most cases, what it does.
These worms are also transparent. This makes them ideal for optogenetics experiments, because the light can penetrate their outer layer and stimulate neurons non-invasively.
What are the findings?
More than 43,000 optogenetic stimuli were delivered to the worms and recorded. From that data, the researchers found:
- By activating neurons in both the head and tail, at the same time, the worms were more likely to 'sprint' forward.
- The probability of a worm reversal was mainly driven by activating neurons in the head.
- Excitatory signals delivered as a worm turns appear to get partially blocked. Activating neurons in the head, for example, was less likely to make a worm reverse if the animal was already turning.
The optogenetics illumination system can track at least 40 worms at once. If a worm moved 200 microns per second, the system's spatial resolution was about 40 microns.
Ten Years of CAR-T
More than ten years ago, Doug Olson was one of three patients to receive CAR-T therapy for his leukemia. For the treatment, a patient’s T cells are removed from their blood, and those cells and are genetically engineered to detect and fight cancer.
You’ve heard the story by now: About 10 million tons of plastic sift into the oceans each year. Engineered microbes can help break apart that plastic. Now there’s an addendum to the story: In areas with a lot of plastic pollution, microbes are more likely to have plastic-eating enzymes. And a French company, called Carbios, launched a pilot plant for recycling PET with microbes in September last year.
Read more in The Guardian.
Palm Oil Replacement
Palm oil — which makes up a third of all oils produced from oil crops each year — is basically destroying the planet. Farming it drives deforestation, including of orangutan and pygmy elephant habitats.
Zero Acre Farms (love the name), based in California, just raised $37 million to produce palm oil from fermentation. Other companies, like C16 Biosciences and Xylome, are trying to do the same. More money in this space should, we hope, lead to some viable, palm oil replacements.
Read more in Tech Crunch.
Cell Squeezing Paper Gets Expression of Concern
There are (at least) two ways to jam new proteins into a cell: electric shocks or by pinching the cell membranes. The latter method, according to a 2018 study in PNAS, caused “dramatically fewer side effects than electroporation and gene expression profiles similar to those of unmanipulated cells” in human T cells.
An expression of concern was issued for the work last week because of concerns “about the reproducibility of some of the results reported in Fig. 2D and Fig. 3.”
Read more in Retraction Watch.