Vilcek Prize for Creative Promise in Biomedical Science
Amit Choudhary has overturned stereotypes and defied expectations throughout his life. Growing up in a community where kids barely completed high school, Choudhary dreamed of becoming a scientist, despite his family’s hopes that he would carry on their farming tradition. Those dreams led Choudhary to become the first in his family to venture abroad and obtain a doctoral degree. Today, as a chemist and biophysicist, he has shattered conventional boundaries between disciplines with remarkable advances in biology. An assistant professor of medicine at Harvard Medical School, Choudhary has earned a place among today’s scientific vanguard, thanks to a rosary of technical feats with a range of potential applications, including improvements to genome editing and treatment of diseases like diabetes and malaria.
Choudhary grew up in a farming community in northeastern India. His father was a store manager, and his mother cared for the family. From an early age, Choudhary fed his scientific curiosity by tinkering with chemicals. When it came time to enroll in college, he chose to study chemistry at the University of Delhi and Indian Institute of Science in Bangalore. Embarking on a quest to widen his prospects, he set out for doctoral studies in the United States in 2006. There, he pursued graduate studies in biophysics with Ronald Raines at the University of Wisconsin–Madison, the move marking a turning point in his career.
In Raines’ lab, Choudhary unveiled the hallmarks of a fundamental force of nature that had largely eluded scientists. Dubbed “n to pi star interaction,” this force is similar to the hydrogen bond, which is crucial for the structural integrity of biomolecules like proteins and DNA. Choudhary predicted that the n to pi star interaction is widespread in proteins and supports their complex structures; experiments later confirmed his predictions. More intriguingly, his work suggests that that the force may have played a role in generating the building blocks of primordial RNA molecules, thought to have jump-started life on Earth. “If you invoke this force, you can explain the prebiotic origin of some of these building blocks,” says Choudhary.
The n to pi star interaction also has more mundane applications: Choudhary revealed that the force shields the negative charge in the common drug aspirin, enabling its entry into cells. (Because the membrane surrounding human cells bears negative charges, similarly charged drugs must overcome the charge barrier to gain entry into cells.) “By using this force, one can essentially shield the negative charge on drugs, and this opens avenues for new modes of drug design and delivery,” explains Choudhary.
Those early findings signaled Choudhary’s scientific promise, promptly securing him a position as a junior fellow in chemistry in the Harvard Society of Fellows in 2011. At Harvard, he set his sights on biology, working with chemical biologist Stuart Schreiber, at the Broad Institute, on pancreatic beta cells, which secrete the metabolic hormone insulin. Dysfunction or loss of pancreatic beta cells results in diabetes, a disease with a devastating toll.
Choudhary addressed beta cell biology from an oblique angle—by examining the extraordinary physiology of binge-eating snakes like Burmese pythons. Though the snakes eat in infrequent bouts, a single meal can deliver upward of 50,000 calories, turning the snakes’ blood into a nutrient-laden goo that resembles yogurt. A similar excess of nutrients would wreak havoc on human pancreatic beta cells, but the snakes have evolved adaptations to deal with the nutrient overload.
Exploring the snakes’ secret to surviving the nutrient glut, Choudhary and his team have found that the snakes’ pancreas nearly doubles in size after a large meal. More to the point, his experiments suggest factors in snake blood that not only protect the snakes’ beta cells but spur the cells to secrete more insulin and ramp up metabolism. Choudhary has shown that some of these factors have similarly protective effects on human beta cells. The hope is that isolating such factors—and unraveling how they protect snakes—will lead to drugs for diabetes.
Choudhary’s accomplishments were also rewarded with an assistant professorship at Harvard Medical School in 2015. While continuing to study beta-cell biology, he has used his training in chemistry and physics to develop technological solutions for diseases that plague the developing world. His current work is centered on an area of fervent scientific interest, CRISPR-Cas9, a tool that has enabled researchers to rapidly and precisely edit the genomes of living organisms. Choudhary has developed activators and inhibitors of the enzyme Cas9 that enhance the enzyme’s efficacy and specificity. The hope is that such modulators will minimize the enzyme’s tendency to make unintended edits to the genome. Eventually, his efforts could lead to ways to correct genetic mutations underlying diseases like monogenic diabetes and combat insect vectors that transmit malaria.
Coming to the United States allowed Choudhary to broaden his scientific purview. “The freedom to leverage one’s training in basic sciences and branch out into different areas is, I think, quite unique to the United States; that freedom allowed me to grow as a scientist,” he says. He adds that he is thrilled to join the roster of recipients of the Vilcek Prize for Creative Promise. “If you look at the list of past winners, it’s a veritable who’s who of biology. As a chemist who is sometimes seen as a biophysicist, I am little bit of an outsider. So I find the honor truly humbling.”
2019 Vilcek Prize in Biomedical Science
Angelika Amon, a leading geneticist and MIT professor, receives $100,000 Vilcek Prize for pursuing new options for the treatment of cancer. Read more about Angelika:
2019 Creative Promise Prizes in Biomedical Science
Congratulations to fellow winners of the 2019 Creative Promise Prizes! Read more about Jeanne T. Paz and Mikhail G. Shapiro:
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