Published by the Students of Johns Hopkins since 1896
April 27, 2024

Big truths from small molecules

By ENOCH TOH | October 2, 2023

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ARGONNE NATIONAL LABORATORY  / CC BY-NC-SA 2.0

Toh shares his personal passion for molecular bioengineering research and reflects on his experience as an undergraduate researcher at Hopkins. 

Ever since I was young, I have been captivated by the intricacies of the small and unseen. While many are drawn to the grandeur of mountains, the vastness of oceans, or the breadth of the cosmos, I found myself enchanted by wonders that lay hidden to the naked eye. From gathering small stones that narrated tales from ages gone by, to admiring the intricate designs of a leaf's veins, these small spectacles have always held my fascination.

This interest in the minuscule wasn't just about their size, but the profound realization that the smallest of entities often hold secrets to the most expansive of phenomena. I began to grasp that understanding the tiny could lead to revelations about the vast.

My early childhood curiosity has shaped my present interest in molecular bioengineering, a field that aims to understand and manipulate biological systems at the molecular level. As a freshman last fall, I joined the Hai-Quan Mao Lab at the Institute for NanoBioTechnology. My lab works on engineering novel biomaterials for regeneration, therapeutic delivery and immune engineering. 

Specifically, I am part of the gene delivery subgroup that focuses on developing lipid nanoparticles (LNPs) as carriers for drug delivery. It is awe-inspiring to think that these minuscule carriers, often just tens of nanometers, have the potential to revolutionize how we deliver therapeutic agents to specific sites within the body. For example, mRNA COVID-19 vaccines utilize LNPs to protect their therapeutic cargo and facilitate uptake by cells. 

As an undergraduate researcher, every experiment I undertake reaffirms my childhood belief: Understanding the intricacies of the microscopic can have a profound impact on the broader scope of human health. 

Working closely with mentors and peers, I have gained hands-on experience in formulating and characterizing nanoparticles, performing downstream functional assessments and using screening platforms to optimize LNP composition. I am also fortunate to have been given the opportunity to incorporate my computational background into my projects. My current work focuses on developing machine-learning-guided automated high throughput screening platforms to inform the development of LNPs for blood-brain barrier penetration and T-cell transfection, which are historically challenging drug delivery targets. 

For me, research is more than just an academic pursuit — it is an embodiment of personal agency. Conducting wet lab research has presented me with the unique opportunity to place curiosity in the driver’s seat for steering my endeavors. In doing so, I have come to see that research is not solely about sterile facts or repetitive procedures. Rather, research is about leveraging precise methods to craft a story, to illuminate new and exciting ideas. I enjoy my research because I am permitted, even encouraged, to dive deeply into my interests, all the while working toward a practical goal with translational impact in the real world.  

Research also provides a robust framework that fosters meaningful teamwork. This collaborative spirit is evident in partnerships between labs, institutions and even among members within a single lab. The structured methodologies intrinsic to research serve as a unifying platform, bringing together individuals from diverse backgrounds and with distinct expertise. Together, they work toward shared objectives, producing outcomes that transcend what any single person or group can achieve independently. 

The collaborative ethos of research is palpable in the culture of my own lab. Many of our projects thrive on intergroup cooperation, and we often work with other labs. For instance, as we develop nanoparticles, we collaborate with labs specializing in specific disease models, leveraging their expertise to enhance the delivery of therapies. Associating research with just breakthrough papers and Nobel-prize-winning discoveries is insufficient because research is more about incremental advancements that accumulate to realize monumental change. 

Research is multifaceted not only in its objectives but also in its approach. Even with similar experimental skills, there is a vast difference between the conduct of foundational, discovery-driven research and applied engineering studies. The mindset and standards differ when comparing high throughput research to rigorous mechanistic studies. Moreover, there lies novelty in both the development of new platforms and techniques as well as in applying established systems for real-life purposes. To that end, one of the privileges of being an undergraduate is the opportunity to delve into these varied research avenues for exploration and self-discovery. My experiences now as an undergraduate will give me a firm foundation for my journey beyond college when I can focus on more specialized topics.

Undoubtedly, research is very challenging. A researcher is responsible for ensuring that every claim is substantiated with concrete evidence. This means that experiments must be conducted with meticulous attention to every detail. More often than not, plans do not unfold as anticipated, and we are forced to reassess and recalibrate our approach. An analogy that resonates with me likens the research process to farming. Much like farming, research involves painstakingly sowing seeds and patiently nurturing them over time, all in anticipation of a fruitful yield. The nonlinear trajectory of research can at times be frustrating, but it is these very hurdles and the eventual breakthroughs that make the journey worthwhile.

Forging ahead, I will continue to carry with me the enthusiasm and wonder that first set me on this path. As I look ahead to my future in research, I am driven by the deep-rooted desire to continuously explore, understand and never stop being amazed by the intricacies of an unseen microscopic world that so deeply captivates me.

Research on the Record spotlights undergraduate students involved in STEM research at Hopkins. The goal of the column is to share reflections on the highs and lows that Hopkins students experience in their contributions to undergraduate research. If you are an undergraduate researcher interested in being profiled, reach out to science@jhunewsletter.com. 


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