For my practicum, I decided to do undergraduate research with Dr. Kluada, of Chemical & Biomolecular Engineering. I was introduced to this lab through my department. In the Clark School of Engineering, students are assigned a faculty mentor. We meet with these mentors every semester for guidance on how to navigate the major, aligning with our interests and career intentions. I expressed my interest in Dr. Klauda’s research through my connection as his faculty mentee.
In Dr. Kluada’s lab, we simulate biological lipid environments (like cell and organelle membranes) via computational tools. To begin, we have to determine what environment we are modeling. Membranes around the body all vary in complexity and composition, so we have to tailor our systems to represent what exactly is being modeled. The key component is the lipid distribution. There are thousands of individual lipid structures in the human body, and they fall into dozens of categories: sphingolipids, sterols, phospholipids, and glycerolipids, just to name a few. Properly selecting these lipids is critical for the accuracy of the modeled membranes' structure and behavior. Simulations are also dependent on additional parameters, including what ions are present and in what concentration, as well as how hydrated the system is. After assembling the system through the CHARMM membrane builder, I export these files to the UMD Zaratan high-performance cluster, a collection of hundreds of powerful computational nodes. Then, I write scripts to define how the simulation should run. Most importantly, how many iterations per dynamic simulation, or how ‘long’ we run the sim. Each iteration performs thousands to millions of calculations (depending on system size), with each time step equating to 2 femtoseconds of real time (2*10^-15 seconds).
My job at this lab is to investigate beryllium toxicity. Before I get into that, I’ll talk a bit about the role of calcium in membranes. Calcium ions are found in essentially all eukaryotic cells, contributing to the function of the plasma membrane and endoplasmic reticulum. In these membranes, calcium binds to negative phosphate and carboxyl groups, which facilitates packing density and lipid order, giving structure to the membrane. Additionally, calcium regulates signaling and transport in membranes by maintaining the potential differences inside/outside the cell. So, calcium is critical for the proper function of fundamental processes in membranes, and this is where beryllium interferes. Be and Ca belong to the same chemical family, alkaline Earth metals. This means they exhibit similar properties, thus bonding affinities. However, beryllium is a much smaller atom than calcium, so it forms much tighter, stronger bonds. When Be atoms contact membranes, they can kick off the Ca ions in favor of the stronger bond. In turn, beryllium discoordinates the membrane and shifts the chemical gradient produced by calcium, altering the potential difference. My job was to analyze the extent to which beryllium intrudes on calcium bonding over various membrane structures and in various chemical environments. One of my discoveries was membranes of higher PS and CL content. PS, with both phosphate and carboxylic groups, bonds uniquely well with Ca. CL has multiple phosphate groups that coordinate with Ca to form a strong bond that prevents Be intrusion. Both of these lipids are found in neurons and cardiac tissue. My experiences in this lab were quite eye-opening, seeing the immense computational effort required to emulate the smallest fragment of biology for mere nanoseconds. It is truly incredible how billions or trillions of atomic interactions underlie every biological process.
I always associated Chemical Engineering with materials; oil & gas, plastics, food products, and consumer products like hand wash or shampoo. Coming into my studies at UMD, my expectation was to be working with something physical. Originally, I was most interested in electrochemistry, and I planned to focus my research on battery and semiconductor chemistry. However, incredible advancements in instrument precision and computing power in the past decade have introduced entirely new fields to ChemE. Molecular biology is fundamentally macro-chemistry. As I’ve been exposed to this novel work, I’ve developed a strong interest and appreciation for the biological applications of ChemE work. My experience has encouraged me to shift my prospects and pursue a more medical-focused future, like pharmaceuticals.