Mayo summer program trains high school researchers who get results  
 

When Kristi Biswas reached the end of 10th grade last year, she'd had about as much formal exposure to science as most high school students her age. "Just biology, chemistry and a little bit of physics," she says. She might not have anticipated she'd soon make meaningful contributions to Alzheimer's research.  

But last summer she spent 10 weeks as part of the SPARK Research Mentorship Program at Mayo Clinic in Florida. SPARK stands for Science Program for the Advancement of Research Knowledge. In the lab of neurologist and neuroscientist Nilufer Ertekin-Taner, M.D., Ph.D., Biswas learned benchwork and genome analysis techniques and conducted her own research project studying Alzheimer's disease.

"I learned about DNA replication, the different proteins associated with Alzheimer's disease, single nucleotide polymorphisms, the biology behind genotyping, and also about coding to do regression analyses," Biswas says. 

Biswas is one of three high school students from last year's SPARK program who produced laboratory research results and presented them in local, regional and state competitions, advancing all the way to the International Science and Engineering Fair in May. The U.S.-based competition was held this year in Atlanta and was attended by more than 1,500 students from 70 countries.  

SPARK student Emma Chirila presented her findings from working in the lab of cancer biologist Debabrata Mukhopadhyay, Ph.D., addressing drug resistance that occurs in pancreatic cancer treatment.  

Andrew Liu, who worked in the lab of hematologist-oncologist Hong Qin, M.D., Ph.D., presented the results of his project aimed to improve immune-stimulating chimeric antigen receptor-T cell therapy (CAR T cell therapy) for acute myeloid leukemia.

Biswas, who ultimately won second place in the Biomedicine and Life Sciences category at the international event, presented her finding of genetic variants associated with the build-up of proteins in the brain that occurs in Alzheimer's disease.  

Tackling Real-World Biomedical Questions 
The SPARK summer program, launched in 2017, introduces motivated, talented, science-minded high school students to rigorous thinking about real-world biomedical questions as they work in Mayo's world-class labs. Nearly 30 established scientists on Mayo Clinic's campus in Florida are on the roster as mentors, volunteering lab space and time to take on the fledgling researchers and get them up to speed.  

Students have gone on from SPARK, not only to compete in science fairs, but to pursue STEM majors in college and additional research opportunities.  

"The students start off with little knowledge about any particular field," says John Copland III, Ph.D., faculty director for the program. "Sometimes they're nervous and even a little shy. But these are extraordinary kids — very smart and very curious." 

Students apply by proposing a research experiment that aligns with a particular lab's expertise. Biswas chose to submit an application to Dr. Ertekin-Taner's lab for a personal reason — a family member who died from Alzheimer's Disease.

"I definitely wanted to pursue research in that area so that hopefully in the future, I might find a therapy target for Alzheimer's, so no one else has to go through losing a family member in the same way," she says. 

Chirila was drawn to research pancreatic cancer because of its poor prognosis and the few treatments available. Her project focused on altering the metabolism of pancreatic cancer cells after she came across an article that linked macropinocytosis — one way that cells scavenge nutrients — to a protein involved in pancreatic cancer.

"I had learned about macropinocytosis in my biology classes but had no idea that it could play a role in cancer," she says.  

From the Basics to Research Results 
Throughout the summer, SPARK students learn experimental techniques, weathering standard lab frustrations like bubbles that get into pipettes and samples that evaporate in the centrifuge. Stephanie Oatman, a Ph.D. student in molecular and cellular biology at Mayo Clinic Graduate School of Biomedical Sciences, jumped at the opportunity to be part of the intensive SPARK teaching. Her research in Dr. Ertekin-Taner's lab focuses on investigating a specific set of genes suspected to be involved in Alzheimer's disease.  
 
She and neuroscientist Mariet Allen Younkin Ph.D., mentored Biswas daily, helping to shape the experiments and teach new concepts.

"We started from basics, and I asked Kristi what she knew, so I could gauge where she was," Oatman says. "We looked at the big picture and worked down to smaller details, so DNA, RNA, proteins — how they're all interconnected and then how they cause disease."  

Biswas kept a binder of journal articles, marked up with her questions and notes. Using genotyping techniques she learned, she examined brain tissue samples from the Mayo Clinic Brain Bank to ascertain whether genetic variants previously discovered by the Ertekin-Taner lab also were responsible for influencing Alzheimer's disease pathology. Her investigation provided a view of the variants in 2,000 samples, and she compared her results to genetic information from publically available datasets. Oatman also taught her the R coding language that the lab uses to conduct genome analyses.  

Using the coding program, Biswas determined one genetic variant associated with brain levels of Alzheimer's disease-related proteins also was associated with disease-related features, like the amount and location of tau and amyloid deposits.

"I was so excited when I saw that association," Biswas says. "That was a really happy day."

"Her results provide additional information about the variants that contribute to Alzheimer's disease," says Dr. Ertekin-Taner. "They'll absolutely be the basis of further investigation and will help prioritize our future studies." The findings will be included in an upcoming journal article that the lab is developing, and Biswas will be listed as a co-author. 

Biswas is excited to attend this summer's SPARK program in another lab where she'll expand her knowledge of neurodegenerative diseases.

"I would definitely say SPARK is a life-changing experience. It gives you a chance to connect with people who have the same passion for science that you do," she says. "I wasn't really a basic science person, but once I got into research, I realized how fun it is and really limitless. There's no end to what you can learn." 

- Kate Ledger, June 2, 2022

• To read more about the SPARK program see their website.
• To learn about Dr. Ertekin-Taner's work, read about her team's recent publication.

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