May 10, 2016 - Current Issue
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What is CRISPR

What is CRISPR

In the Molecular Biology lab class of Christopher Phiel, PhD

Phiel connects undergrads with the very latest technology
Even if you aren't a biomedical researcher, you may already have a passing familiarity with the easy-to-remember acronym CRISPR from recent news reports:

"CRISPR'S unprecedented ability to edit genetic code will make possible a new generation of medical treatments."  The New Yorker, Nov. 16, 2015

"… the range of potential uses is so huge—everybody wants in."  The New York Times, Nov. 15, 2015

"CRISPR is turning everything on its head."  Nature, June 3, 2015

Read more extensively about CRISPR (pronounced "crisper") and you may also see references to the elimination of mosquitoes that carry the Zika virus, the editing of HIV-1 DNA out of the genome of human immune cells, and the possibility of CRISPR leading to a Nobel Prize.

Now this revolutionary gene-editing tool has arrived at CU Denver College of Liberal Arts and Sciences in the Molecular Biology lab class of Assistant Professor Christopher Phiel, where students are using CRISPR to edit the genome of a cell.

"This is definitely why I took the class," said senior Sam Altman. "To be learning about something that has the potential to eradicate disease, to take the principles we learn and apply them with real results, to conduct experiments like those being done by the best researchers in the world, this is so exciting."

Think of CRISPR (short for Clustered Regularly Interspaced Short Palindromic Repeats) as very sharp "molecular scissors" that allow researchers to target and precisely edit the genome of any cell in any organism—snipping out a piece of DNA.

Philippe Mukubi works on his CRISPR project

Philippe Mukubi works on his CRISPR project

In the past, editing one gene could take years. With CRISPR, it can take just days. The implications are staggering. CRISPR could turn off disease triggers, develop crops that are pest and drought resistant, eliminate malarial mosquitoes and speed up the creation of new drugs. While CRISPR can trace its beginnings to research done in the late 1980s, the technique has exploded on the scientific scene in the past two years.

Last year, Phiel, an NIH-funded investigator, took a look at how CRISPR was being used to manipulate DNA and realized that it was not much more difficult than what his students were already doing in his lab. He set aside three weeks for students to learn about CRISPR and quickly learned it wasn't enough time. This year, he turned those three weeks into a full semester lab, which his students are taking after a semester of preparatory lectures.

Walk into Phiel's lab and you see eight two-person teams, each working on a different gene they are trying to CRISPR. All the concepts they learn in a molecular biology lab—the unrelated tools in their toolbox—get put to use in CRISPR. The students are engaged, on task, collaborating and excited that they are working with a technique that has so much potential.

"No doubt there are other schools doing this, but I think we may have been among the first state universities in the country to have undergraduates CRISPRing as part of a course," Phiel said. "This takes the abstract concepts that students learn in a lecture and lab and gives them purpose and real-world application through hands-on experimentation."

"We learned all about this in class," said Ahmad Bedair, a senior headed to medical or graduate school. "Now the challenge is to think about it not just technically, but practically."

Harmony Matshik Dakafay and Ahmad Bedair discuss CRISPER

Harmony Matshik Dakafay and Ahmad Bedair discuss CRISPER

Harmony Matshik Dakafay, a CU Denver graduate taking courses to prepare for a Physician's Assistant program, explained Phiel's CRISPR experiment in a soft-spoken manner that belies the sophistication of the science. "We are trying to insert a mutation into a gene," she said. "If you want to know what a gene does, sometimes you have to knock it out."

Bedair, her lab partner, explained further. "The sequence of DNA determines the traits of an organism. Manipulate the DNA sequence—snip some of it out—and you can manipulate traits."

Matshik Dakafay is thrilled to have the opportunity to learn about CRISPR because the training will elevate her resume when she looks for jobs in research labs. "I love this class," she said. "It's such a good way to understand the mechanics behind a disease."

"As an undergraduate, being at the forefront of modern research is so cool," Bedair added.

Mohammed Alawami learned about CRISPR as a freshman working in the CU Anschutz lab of Randall Cohrs, PhD. Fascinated by the thought that CRISPR could cure viruses, Alawami is now working on a mathematical model that he hopes will increase the success of CRISPR targeting. He calls Phiel's class "a dream come true" and hopes that someday he will be setting up his own biotech company.
"This is what I want to spend my life doing," Alawami said. "When I found this class, the path to the future opened for me."

"Dr. Phiel has such an optimistic outlook on the future of medicine," Altman added. "We are talking about eradicating diseases. It's exciting, it's positive, and Dr. Phiel conveys that."

Phiel calls himself a "guide" and "troubleshooter" for students and acknowledges that his course is not for those who want easy, guaranteed answers. His students spend two entire lab periods just doing analysis and planning before they ask his approval to purchase materials. He believes this process gives them a sense of ownership because they have designed the experiment from step one. Ultimately, they will evaluate the effectiveness of their projects using additional techniques they have learned in the lab.

"Things may not go as smoothly as we hope, but you can also learn a lot from things that don't work," Phiel said. "This is true research."

Ask Phiel if CRISPR is an ambitious goal for undergraduates—a stretch for both the students and the teacher—and he has an emphatic answer. "All of us who teach are passionate," he said. "It makes things more interesting to incorporate the newest research in our areas of expertise and there is a huge benefit for students."

Phiel sees the immediate future of CRISPR to be the cure of diseases such as cystic fibrosis, which is caused by a mutation in a single gene. That is not a fantasy, thanks to the work on CRISPR being done by researchers around the world, and now by undergraduates at CU Denver.

Originally written by Vicki Hildner, University Communications, April 4, 2016

Note: Jennifer Doudna, PhD, one of the researchers credited with discovering CRISPR technology, will be the speaker at the CU Denver Chancellor's Distinguished Lecture Series, presented by the Damrauer Endowed Lectureship Fund, on Oct. 17, 2017. 

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