My Scientific Village

Below is my submission to the 2022 Lasker Essay Award Competition. This year's topic was on the importance of collaboration in science. For this essay, I reflected on my path to becoming a scientist and the people who've shaped me and my science for the better.

My Scientific Village

Only once a week did I experience the joy of science class. There, in my Bronx inner-city public school, I “met” renowned scientific luminaries, such as adventurer Charles Darwin charting the origin of species and the lab-based Robert Koch devising the germ theory of disease. These singular titans, I thought, tirelessly toiled alone, paying the unavoidable price for scientific discovery.

My early fascination with these scientific titans cemented into a passion for research and medicine that led me to pursue an MD-PhD degree at Harvard Medical School. Imitation is often said to be the sincerest form of flattery, and so I too started my PhD journey excited to put my head down and work solitarily to advance the boundary of knowledge. Over the course of my PhD, I learned the most important lessons of doing research: good-faith collaboration was fundamental; professional success often followed suit.

For my PhD thesis, I studied Mycobacterium abscessus (Mab), a bacterium that causes difficult to treat infections. Few antibiotics effectively treat Mab, thus there is a pressing need to develop new therapies against this pathogen. The goal of my project was to identify essential genes in Mab that would make great targets for antibiotics and pave the way for new medicines. As a microbiologist, I could with ease, design and conduct a genetic screen to identify essential genes. However, identifying the best drug targets from the large datasets generated by my screen required computational mining skills to analyze sequence data, detect patterns, and identify the best drug candidates. Embarking on my own expedition from Boston to College Station, for a week I worked alongside Dr. Tom Ioerger, a brilliant bioinformatician at Texas A&M University, to go further together than either of us could have gone alone.

As the trained microbiologist, I identified the genes and pathways most worth probing. I then relayed my insights to Tom, the bioinformatician, who nimbly employed his computational tools to produce captivating representations of our data and generate new, exciting insights for me to pursue. In short, our collaboration was an enriching symbiosis of bioinformatics and bacterial genetics. That week I discovered, finally, the joys of scientific collaboration. That discovery would manifest as one published joint manuscript and 2 joint manuscripts currently in review.

Unlocking the true accelerator capacity of collaboration also changed the trajectory of my PhD. By the end of my week with Tom, we identified a promising drug target called PBP-lipo, a cell-wall synthesis enzyme that was essential for growth in Mab. As a cell-wall enzyme, PBP-lipo represented an attractive target for blockbuster antibiotics like the penicillins. To characterize this never before studied enzyme, I established collaborations with structural biologists, biochemists, and microscopists. Together, we tackled characterizing PBP-lipo using different methods that shed new light into how the enzyme worked. With the structural biologist, we generated structures of PBP-lipo and highlighted unique features of the Mab enzyme. With the biochemist, we purified PBP-lipo to identify its protein binding partners. And with the microscopist, we visualized where and when PBP-lipo was expressed in the cell.

The information gathered from these collaborations led me to set up an exciting new collaboration with Dr. David Nyguen at the Cleveland Medical Center. Our joint mission is to identify molecules that directly bind and inhibit PBP-lipo. Getting to this point of my project was only possible because of the team of scientists who I collaborated with. Together, they helped me traverse several scientific milestones, from conducting a successful genetic screen, to characterizing a novel drug target, PBP-lipo, to eventually screening molecules that inhibit this enzyme and could potentially be used to treat Mab infections.

As an aspiring infectious disease physician-scientist, my career goal is to spearhead research that alleviates the burden of infectious diseases around the world. My PhD experience taught me the importance of collaboration in achieving that goal. Ultimately, my collaborators trained me to be a better scientist and by working together, imbued my science with a robustness that made our observations more exciting and importantly, translatable to the bedside.

Once I experienced the power of collaboration, the always-present thicket of diverse influences on my scientific idols became apparent. I learned Charles Darwin was influenced by geologists, zoologists, and economists whose ideas sharpened his ‘Origin of Species.’ Robert Koch worked with pathologists to develop the ‘Germ Theory of Disease.’ In truth, science back then and certainly science now is collaborative. For science at its core is a continual process of building upon people’s ideas. I cannot wait to take part in this process as a physician-scientist. The toil is more joyous in the presence of a scientific village. I’m just as excited for future discoveries as I am for the expanded circle of collaborators thrilled to study the world around us and make it a healthier place.