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Kinetic Tools to Combat Zika Virus and Advance Biotech Careers




Christal Sohl (San Diego State University, 2016 New Investigator, 2017 Travel Grant) leads a research group that uses "kinetic, structural, and cellular tools to address how altered enzyme activity impacts human health, especially in diseases like cancer." She says, “Right now a major focus of the lab is understanding how metabolic enzyme activity is altered by mutation or environmental stress in the context of cancer.”

“ For me, [CSUPERB] funds allowed us to pursue an interesting problem in genome infidelity that would not have been funded by traditional grant mechanisms. This project was in its infancy, and the CSUPERB New Investigator funds allowed us to generate preliminary data."  In addition, the CSUPERB funding supported a master's student, Anna Uvarova, who used the experience gained in the Sohl lab to land a job at Novartis, a pharmaceutical company. "The CSUPERB Travel Grant provided me…happenstance events – we were able to get some important cell lines from a new collaborator and received exciting feedback on some of our work. These opportunities to make our science more impactful are priceless." 

"The feedback received from the [CSUPERB] study sections is also enormously helpful. Even if one doesn’t get funded, I advise other CSUPERB PIs to think of this as an opportunity for a room full of intelligent scientists to critically assess your ideas…A reviewer on an NIH study section was pleased to see that we were successfully competing for grant opportunities at the university, local, and state levels.” 

Dr. Sohl trained at Vanderbilt University and Yale University, but says “SDSU is a special place for a variety of reasons…Our student population is rich in traditionally underrepresented groups in STEM, perhaps most obviously through our Hispanic-serving institution designation, but we are also recognized for supporting first-in-family students and LGBTQ students. We have a real opportunity to diversify the local workforce by training and mentoring these students in STEM fields. I’ve launched a new cross-university mentoring program, MINDSET (Maximizing INclusion and Diversity in Science, Engineering, and Technology) that has at its heart this very goal. And I’d like to add that the students in my lab are just as talented and just as hardworking as any as I’ve seen at my previous (including higher-ranked) institutions.”

Research pulls open-minded investigators in unforeseen directions, leading to unexpected collaborations and impactful outcomes. Dr. Sohl explains, “Our CSUPERB funding was focused on the kinetic features of human polymerases, but partway through the project, a really exciting collaborative opportunity emerged. We were fortunate that CSUPERB funding allowed us to switch gears a little bit to study the catalytic features of the viral polymerase found in Zika.” Working with SDSU chemist Prof. Byron Purse and UCSD pharmaceutical scientist Prof. Jair Siqueira-Neto, the interdisciplinary team developed Zika polymerase inhibitors and tested the most promising inhibitors in a high-throughput assay in Zika-infected cells and animal models. Dr. Sohl says, “This is directly preparing our students for the types of challenges and opportunities they may face in future industry careers.”

Bernatchez, JA, Yang, Z, Coste, M.,  Li, J, Beck, S, Liu, Y, Clark, AE, Zhu, Z, Luna, LA, Sohl, CD,  Purse, BW, Li, R & Siqueira-Neto, JL. (2018) Development and validation of a phenotypic high-content imaging assay for assessing the antiviral activity of small-molecule inhibitors targeting the Zika virus. Antimicrobial Agents and Chemotherapy.

Captions for photos below:

1) Left to right: Undergraduates Stacy Anselmo, Madison Kennedy, and graduate student Diego Avellaneda Matteo monitor the rate at which a metabolic enzyme binds to its substrate at the millisecond timescale using a stopped-flow spectrophotometer.

2) Christal Sohl trains graduate student Anna Uvarova (now employed at Novartis in Cambridge, MA) to use a rapid quench to measure how quickly polymerases replicate DNA. 
This story is one in a series of PI profiles published in concert with the AY 17-18 CSUPERB Annual Report. Read the report here and find other profiles here.