Defining the Future of CRISPR
For food scientist Rodolphe Barrangou, good scientific research is like a gourmet meal.
“The way we do research at NC State essentially is enabling me to be a great chef,” he said. “I have a fantastic kitchen with my lab facilities. I have a fantastic cooking team with the students and staff that we have. Then we have great recipes that we can use to bring together all those ingredients and make a masterpiece.”
Barrangou’s masterpiece involves an emerging technology that’s one of the hottest buzzwords in science: CRISPR. The Todd R. Klaenhammer Distinguished Professor in Probiotics Research is among the world’s foremost experts in this field. For more than a decade, he and his team have been using different CRISPR sequences to vaccinate dairy bacteria against thousands of common dairy viruses.
In the process, the NC State graduate has co-founded a successful startup, won international awards, mentored the next generation of CRISPR researchers and helped advance genetic research across a wide range of fields. And he and his fellow scientists have only just begun to tap CRISPR’s potential.
What Is CRISPR?
This complex technology originated in nature. CRISPR (short for Clustered Regularly Interspaced Short Palindromic Repeats) is an adaptive immune system in bacteria that enables them to withstand invasive genetic elements like viruses. “Much like we have an immune system, bacteria have an immune system,” Barrangou said. “CRISPR is it.”
In recent years, scientists have harnessed this natural process to create tools that can edit genomes in everything from bacteria to humans. “This technology can be used to cut any piece of DNA that you want,” Barrangou said.
With CRISPR, enzymes generate different kinds of cuts in the DNA. The most common is Cas9, which acts as a kind of molecular scalpel, slicing out targeted DNA sequences that scientists want to remove. Then, endogenous DNA repair machinery comes in and rewrites the DNA sequence precisely at the site of the cut.
Barrangou likens the system to word-processing software. “You can do things like add a gene like you would add a word, remove a gene like you would remove a word, or even add a whole sentence or cut out a whole paragraph,” he said. “You can rewrite or correct the typos.”
In humans, that could mean correcting the genetic typos that lead to deadly illnesses. “If you have a genetic disease and a faulty gene sequence, you can come in, cut it, recognize it, cleave it and replace it with a healthy allele,” he said.
In a few short years it’s gone from being a niche novelty to a scientific craze — with applications in a wide range of fields. “CRISPR is one of those rare technologies that is transcending and altering research and development and genesis of next-generation products in medicine, in agriculture and in biotechnology,” Barrangou said.
The CRISPR Lab
Barrangou’s lab in NC State’s Department of Food, Bioprocessing and Nutrition Sciences has three goals: to understand CRISPR and how it works in bacteria; to use that understanding to develop CRISPR technologies, which use CRISPR in specific ways; and to use CRISPR technologies to generate better bacteria and probiotic strains for use in food.
A primary focus of the lab is improving cultured dairy products like yogurt and cheese. Barrangou and his team use CRISPR technologies to vaccinate the bacteria used to ferment those foods against phage viruses that can contaminate or even destroy the starter cultures. This process yields more consistently high-quality products that stay fresher for longer.
Their work also helps make the dairy products we eat healthier. “We use CRISPR-Cas in probiotic strains to enhance their features and their functional attributes, to drive their survival in the GI tract and enhance their ability to make us healthier and better and happier,” he said.
According to Barrangou, this process has been so successful that it’s now incorporated in every commercially produced dairy product. “That means if you’ve had one wedge of cheese, one nacho, one slice of pizza, one cheeseburger, one bite of yogurt, anywhere from China to Argentina, you’ve consumed a CRISPR-enhanced dairy product,” he said.
Since Barrangou published one of the earliest research papers on CRISPR in Science in 2007, his profile has risen along with CRISPR’s. He is widely recognized a leading authority on the technology, and the accolades are piling up.
This year, he’s been elected to the National Academy of Sciences and won the academy’s Prize in Food and Agriculture Sciences. And in 2016, he won a Canada Gairdner Award and the Warren Alpert Foundation Prize, two of the field’s most prestigious medical research prizes.
Out of the Lab
Barrangou has made it his mission to help inform the public about the importance of CRISPR. Breaking down this complex science — and helping people understand its relevance to their lives — isn’t easy.
“It’s a sizable challenge. It requires the ability to communicate much better, to educate the public about the great scientific revolution that’s before us,” he said.
One way he does this is by serving as the first editor-in-chief of the new CRISPR Journal, which aims to drive the field forward by sharing research from and with scientists around the globe. “It’s an exciting hat to wear, and it’s really opened up my mind as to what the boundaries of science are,” Barrangou said.
He also co-founded Locus Biosciences, a biotechnology company based in Research Triangle Park that develops next-generation precision antimicrobials using CRISPR technologies. The startup grew out of his lab’s work.
“One of the great things we do at NC State is not just making the next generation of successful alumni, not just coming up with the next generation of technologies, not just enhancing our scientific knowledge of the world — we want to be entrepreneurial,” Barrangou said. “We take it out of the lab and into the marketplace.”
The Future of CRISPR
Currently, the potential of CRISPR seems endless, and Barrangou is determined to keep pushing the boundaries.
Scientists are currently exploring how to harness the different functions of the various enzymes that can be used to generate cuts in the DNA. Cas9 has been the standard for years, but Barrangou’s team has also been working with Cas3, an enzyme that cuts the DNA of a bacterial cell and then essentially chews it up beyond repair, destroying the cell.
“Most people right now use a very small number of CRISPR-Cas systems that have been characterized,” he said. “There’s a gold mine that exists in nature that we’re continuing to unearth.”
This potential for improvement and discovery is what keeps Barrangou coming to the lab every day. He knows CRISPR is already helping the world, but he wants to keep making it even better.
“We’re working on enhancing and developing those CRISPR tools, to make next-generation tools that are better, that are leaner, that are faster, that are more affordable, that are more potent, to really go into the next phase of the CRISPR craze,” Barrangou said. “This is just the beginning.”