Triple play in science communication

We are highlighting Emory BCDB graduate student Emma D’Agostino, who is a rare triple play in the realm of science communication. Emma has her own blog, where she talks about what it’s like to have cystic fibrosis. Recent posts have discussed the science of the disease and how she makes complicated treatment decisions together with her doctors. She’s an advisor to the Cystic Fibrosis Foundation on patient safety, communicating research and including the CF community Read more

Deep brain stimulation for narcolepsy: proof of concept in mouse model

Emory neurosurgeon Jon Willie and colleagues recently published a paper on deep brain stimulation in a mouse model of narcolepsy with cataplexy. Nobody has ever tried treating narcolepsy in humans with deep brain stimulation (DBS), and the approach is still at the “proof of concept” stage, Willie says. People with the “classic” type 1 form of narcolepsy have persistent daytime sleepiness and disrupted nighttime sleep, along with cataplexy (a loss of muscle tone in response Read more

In current vaccine research, adjuvants are no secret

Visionary immunologist Charlie Janeway was known for calling adjuvants – vaccine additives that enhance the immune response – a “dirty little secret.” Janeway’s point was that foreign antigens, by themselves, were unable to stimulate the components of the adaptive immune system (T and B cells) without signals from the innate immune system. Adjuvants facilitate that help. By now, adjuvants are hardly a secret, looking at some of the research that has been coming out of Emory Read more

CRISPR/Cas9

Four hot projects at Emory in 2017

Once activated by cancer immunotherapy drugs, T cells still need fuel (CD28)

— Rafi Ahmed’s lab at Emory Vaccine Center. Also see T cell revival predicts lung cancer outcomes. At Thursday’s Winship symposium on cancer immunotherapy, Rafi said the name of the game is now combinations, with an especially good one being PD-1 inhibitors plus IL2.

Pilot study shows direct amygdala stimulation can enhance human memory

— Cory Inman, Joe Manns, Jon Willie. Effects being optimized, see SFN abstract.

Immune responses of five returning travelers infected by Zika virus

— Lilin Lai, Mark Mulligan. Covered here, Emory Hope Clinic and Baylor have data from more patients.

Frog slime kills flu virus

— Joshy Jacob’s lab at Emory Vaccine Center. A follow-up peptide with a name referencing Star Wars is coming.

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Manipulating mouse genes to order, CRISPR or old-school

Just a follow-up to last week’s announcement from the Emory Transgenic Mouse and Gene Targeting core that they are offering CRISPR/Cas9 gene editing for mice. Using CRISPR/Cas9 to produce genetically altered mice is a

Knockout_mice

Gene targeting – the 20th century way

substantial advance over the old way of doing knockouts and other manipulations (which itself won a Nobel Prize in 2007), mainly because it’s faster and easier.

To appreciate the difference, consider that the old way involves introducing DNA into mouse embryonic stem cells, and then selecting for the rare cells that take up and incorporate the DNA in the right way. Then the ES cells have to be injected into a blastocyst, followed by mouse breeding to “go germline.”

With CRISPR/Cas9, it’s possible to inject pieces of RNA that target the desired genetic changes, straight into a one-cell stage mouse embryo. Not every embryo has all the right changes, but the frequency is high enough to inject and screen. As this review explains, it’s possible to introduce mutations into three genes at once and get mice quickly, rather than make each one separately and then breed the mice together, which can take many months.

Also, because of the need for drug selection, the targeting construct in old-school gene targeting has to be a blunt instrument. That can make it hard to make subtle changes to a gene — like introduce point mutations corresponding to natural variations linked with human disease — without taking a sledgehammer to the entire gene locus. CRISPR/Cas9 takes care of that problem.

Despite the advantages of this technology, three things to keep in mind:

*Many genetically altered mice are already available “off the shelf” as part of the International Knockout Mouse/Mouse Phenotyping Consortium.

*Emory’s Mouse Core has been working with the company Ingenious Gene Targeting, and has been out-sourcing some of the tedious aspects of old-school gene targeting in mice to Ingenious, starting last year. Technicians there can generate a dazzling array of conditional knockouts. If you want your favorite gene to flip around and produce a fluorescent protein when you give the mice an antibiotic, but only in some cells — Ingenious can do that. Old school is actually still the way to go for fancy stuff like this.

*Jackson Labs in Maine also works with Emory, offering similar services, and offers a guarantee. Read more

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