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A Sweet Spot For Chemistry

Chemistry is key to Dr. Karina Mariño’s research at the Instituto de Biología y Medicina Experimental, where she studies the role of glycans.

It all began with a chemistry set—a gift from her father when Dr. Karina Mariño was eight years old. He recognized and encouraged her curiosity, especially since he was unable to complete his own education. Juan Mariño Traba and his daughter were also avid readers. Their bounty of books opened her imagination to explorers, magicians and alchemists.

Dr. Mariño has vivid memories of mixing things and experimenting—laying the foundation for a future life in the lab. But her interest waned as she gravitated toward writing and archaeology. Then her high school chemistry teacher, noticing her fascination with formulas and lab experiments, re-ignited her interest. Now, chemistry is key to Dr. Mariño’s research at the Instituto de Biología y Medicina Experimental (IBYME) in Buenos Aires.

There’s Nothing Simple About Sugars

The road to research wasn’t a straight one. In fact, it took Dr. Mariño from Buenos Aires to Scotland and Ireland and back again. Along the way, she discovered the ubiquitous and complex role of sugars in biological processes.

Dr. Mariño studied carbohydrate chemistry as an undergraduate and PhD student. She was supervised by Dr. Rosa Lederkremer and Dr. Carla Marino at the University of Buenos Aires. But those years coincided with the 1998-2002 Argentine Great Depression. Her country suffered severe upheaval, collapsing from its height as Latin America’s third largest economy.

So, when it came time to seek postdoctoral training, Dr. Mariño looked northward. Her PhD supervisor, Dr. Lederkremer, had collaborated with Dr. Michael Ferguson at the University of Dundee in Scotland. Through that connection she found an enticing project in biological chemistry and dramatically different locale. She was cautioned about Dundee’s coastal summers (decidedly cooler) and size (a mere 1% of Buenos Aires’ 13 million residents). But she could learn more about glycobiology, looking for potential drug targets for African sleeping sickness.

Her next postdoctoral stop was Dublin, Ireland, with Dr. Pauline Rudd at the National Institute of Bioprocessing, Research and Training. Dr. Mariño continued her foray into glycobiology, addressing the role of carbohydrate-rich mucus in mediating bacterial interactions in the gut. Under Dr. Rudd’s mentorship, she also found passion and rationality intertwined in scientific research. She recalls Dr. Rudd’s maxim, “The head in the sky, the hands in the bench.”

New Beginnings, Big Ideas

Dr. Mariño presenting her research at our 2018 Innovations Symposium. Photo credit: Mitch Tobias

After six years, Dr. Mariño made the difficult decision to return to Argentina, leaving behind resources and opportunities. But the pull home was strong, not least of which was her family. She could also give back to the public education system that made her university and doctoral education possible.

Dr. Mariño landed at IBYME, a pioneering center founded by Bernardo Alberto Houssay. He was the first Latin American Nobel Laureate in the sciences and a champion of future researchers.

While she started her lab with little more than a desk, Dr. Mariño was full of ideas. She was particularly fascinated by the complex interplay of carbohydrates and immunity in the intestinal tract, and how it influenced development of Inflammatory Bowel Disease. She sought out Dr. Gabriel Rabinovich, who mentored her in the intricate world of immunopathology. And in 2015, they turned to the Kenneth Rainin Foundation with two big ideas.

Unlocking the Secrets of Sugars

Dr. Mariño’s idea centered on the role of glycans—complex sugars on cell surfaces—during the course of IBD. Glycosylation, a process where carbohydrates are attached to proteins, can be altered by inflammation. Dr. Rabinovich drew from his earlier work on Galectin-1, a protein that recognizes certain types of glycans. His findings indicated Galectin-1’s biological role as an anti-inflammatory agent in chronic diseases like rheumatoid arthritis.

They proposed a cross-disciplinary collaboration to investigate how altered glycosylation and Galectin-1 anti-inflammatory properties might influence intestinal inflammation. Could a protein’s ability to modulate inflammation, in combination with specific cell glycans as receptors, unlock new therapeutic approaches?

Funding from the Rainin Foundation was essential to the long, arduous work that began with their novel idea. Optimizing the experimental models to establish their line of research took nearly two years alone. And Argentina—its economy still struggling—is isolated from more concentrated sources of international funding in the north.

Even so, Dr. Mariño and Dr. Rabinovich’s collaborative ideas have borne fruit. They were able to show how Galectin-1 helps to promote resolution of the inflammatory process in the intestinal tract. But there are more secrets to unlock behind Galectin-glycan interactions. One project will examine the proinflammatory profile of Galectin-4 and its influence during Inflammatory Bowel Disease development. And deep within each new biological question, Dr. Mariño knows she’ll find chemistry.

The Kenneth Rainin Foundation is celebrating 10 years of formal grantmaking in 2019. To mark this milestone, we are sharing “10 Stories For 10 Years,” a series that pays tribute to the incredible work of our grantees and what we’ve learned along the way.

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