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CRISPR-Cas9 and the Brain: Commentary From a Symposium Speaker at the ASPET Annual Meeting

July 21, 2017
By Tamara Escajadillo

Whether or not you were able to attend the ASPET Annual Meeting at Experimental Biology 2017 (EB 2017) in Chicago, I have no doubt that you have heard of the CRISPR-Cas9 system and its potential applications in the field of biomedical research. In this interview, we will talk with newly minted PhD recipient and “CRISPR-Cas9 Revolution in Pharmacology” invited symposium speaker at ASPET’s 2017 annual meeting Alex Sandweiss, from the University of Arizona. 

How did you decide to attend the ASPET meeting? 

Alex: I was fortunate enough to give a short talk about our research in the Vanderah lab last summer at the International Narcotics Research Conference (INRC) in Bath, UK. Drs. Susan Ingram and Lakshmi Devi were at the meeting and recommended I participate in the “CRISPR-Cas9 in Pharmacology” symposium at EB 2017. I was absolutely honored to be invited to discuss our research at this incredible symposium, and it was a no-brainer for me to attend. 

Had you attended an ASPET meeting before? What was your experience at this year’s meeting? 

Alex: I had previously been to the ASPET Annual Meeting at EB 2013 in Boston. In fact, that was one of my first professional meetings, which as we all remember, is an incredibly overwhelming experience. This time around, I was much more comfortable with presenting and with absorbing all the new, fascinating research that’s happening across the globe. The ASPET meeting (and EB at large) also allows for the opportunity to see how other fields within biology—besides my own of neuroscience and opioids—are evolving. I had fantastic conversations with several undergraduates, graduates, post-docs, and med students alike about their research from other disciplines and about their career paths. I wish it was possible to stop at every poster, attend every talk, and discuss every detail, but unfortunately, we haven’t cloned adults yet…maybe at next year’s EB. 

What was your experience taking part in the “CRISPR-Cas9 Revolution in Pharmacology” symposium? 

Alex: First of all, what an amazing symposium Drs. Tonsfeldt and Devi put together. I was honored to be a part of the exceedingly relevant discussion about CRISPR, particularly in today’s scientific climate. Every biologist is aware of the potential for genetic engineering; all we’ve needed is an efficient, rapid, and reliable method to switch to the next gear in basic and clinical sciences, and the discovery of CRISPR and its subsequent application in the life sciences has provided that opportunity. This was brilliantly addressed by the other speakers at the session, who provided unequivocal evidence for CRISPR’s utility in treating genetic diseases such as Duchenne muscular dystrophy, manipulating the immune system, and altering the respiratory system! While listening to the other speakers, I often forgot I had to give a talk of my own. I was amazed listening to Dr. Gersbach discuss the characterization of CRISPR at the molecular level, and was constantly challenged with new ideas and questions I had never thought of. To me, that is the single greatest importance of attending meetings and presenting data—to spread the ideas of your lab out to the greater scientific community, and to gather ideas right back to bring home. It is clear after that symposium that there are unbelievably creative ideas out there to utilize CRISPR in new, interesting ways. 

Can you briefly describe your research project and what inspired you to make animations about your work? What kind of feedback have you gotten about your animations? 

Alex: The data I presented at the CRISPR-Cas9 symposium at ASPET’s 2017 annual meeting (and my main PhD project from my time in the lab of Dr. Todd Vanderah at the University of Arizona) enforced how the neurokinin system potentiates opiate reward. The neurokinin system includes the neurotransmitter substance P (SP), which we largely regard as a pro-nociceptive mediator activating NK1 receptors on the post synaptic (or second order) neuron in the dorsal horn of the spinal cord. Previous research over the decades has also shown that SP plays an integral role in activating dopaminergic neurotransmission in the ventral tegmental area (VTA), propagating reward signals in the nucleus accumbens (NAc). By utilizing CRISPR and pharmacologic tools, we demonstrated that opiates increase the release of SP in the VTA via disinhibition of GABAergic interneurons. This increase leads to activation of NK1 receptors on dopaminergic neurons, which potentiates the reward pathway in the limbic system. We used CRISPR to knock out the NK1 receptor gene in the VTAs of live adult rats, which was sufficient to block the chemical signature of reward (dopamine release in the NAc), and the behavioral correlate of addiction (conditioned place preference for morphine). 

I never want to be a boring speaker who loses their audience with a topic that not everyone finds as captivating. Additionally, I have an interest in relaying scientific concepts to broad audiences outside biology. Therefore, I decided to learn how to animate my dissertation. I tested my animations out on my lab-mates and friends, and I received constructive feedback from Dr. Vanderah and others, refined the animations, and then included them in my PhD oral defense. The end of my defense was one of my prouder moments when faculty prefaced every question with “wow, those animations.” I knew the animations were a unique aspect of the talk and may even make the talks memorable, which is important for any student or young investigator beginning the (hopeful) ascent through their career. 

Do you hope to run your own research laboratory in the future or remain on the clinical side only? Have you thought about how you will be able to use what you've learned from your research in the clinic? 

Alex: My goal is to one day run my own basic science lab and hopefully allow my research to translate into the clinic. I will be graduating medical school in 2018 and moving on to residency in pediatric neurology. There, I will be able to refine the clinical skills necessary to practice neurology in children while exploring my interests further and maintaining a presence in basic science and clinical research. At the end, I hope to begin my career as an independent physician-scientist studying the amazing things that happen in the brain—and the devastating ways they can fail—in order to contribute whatever I can to the ever-growing puzzle of the brain and positively affect patients’ lives. 

Thanks to Alex for his participation in this interview, as well as all those who participated in the “CRISPR-Cas9 Revolution in Pharmacology” symposium!

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Last Updated: September 6, 2017

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