Author Archives: Sam Shi

Before the program started, I set the goals of “practicing how to think and tackle problems like a researcher and figuring out whether doing basic science research is what I want.” As the program comes to an end, I’m starting to realize my most important takeaway is that I love being a student. Students learn the answers to questions. Scientists are but a special kind of student. They can’t find answers in a textbook or from a teacher, but they must seek answers from the natural world itself. Choosing a career in research would mean becoming a life-long student. It’s exciting, intellectually stimulating, and rewarding. Before BSURF, I often said that I’m interested in research. Now, I’m certain that research will be a part of what I do in the future. 

One other thing I would mention is that this program has provided numerous opportunities for practicing how to communicate science. How much communication is involved in a career in science is also something I didn’t understand before. In addition to doing research in the lab, I really enjoyed the seminars and workshop sessions that this program offered. Finally, I would like to thank Rachel, Dr. Ko, members of the Ko lab, Dr. Grunwald, Dr. Harrell, and Austin for making this wonderful experience possible.

Through a series of unexpected events, a young doctor who had just graduated from med school found himself in a prestigious program designed to train physician scientists. Dr. Lefkowitz, who had never thought about doing research before, experienced failure for the first time. The two-year training program was eventually successful, but he struggled in the process. Biomedical research proved to be more difficult than anything he had done before. During residency, Dr. Lefkowitz discovered that he actually missed the challenges of research, and he decided to dedicate a large part of his career to basic science research.

This faculty seminar from Tuesday given by Professor Lefkowitz made me think a lot about what I want to do with my life. His speech made me excited about doing research, and more importantly, his advice was valuable. Here are some of the talkaways I got from his talk. Building a career around scientific problems is better than building one with lab techniques. Learning new lab techniques takes a lot of time and effort, and it can be particularly difficult when one is already very comfortable with a set of techniques. However, as scientists, it’s more important to learn whatever that’s necessary for answering the scientific questions. Viewing work as play makes doing research fun. I resonate with Dr. Lefkowitz’s point of how intellectually stimulating the process of asking questions, forming hypotheses, and designing experiments is. Don’t talk oneself out of an experiment. Sometimes taking risks can provide surprising results, and a lot of scientific discoveries were made this way.

The innate immune system is highly complex with its intricate maps of signaling pathways and hard-to-remember, long protein names. It’s quite remarkable that this large network can detect pathogens, initiate a number of intracellular processes, and signal for a coordinated body-wide response. Lauren’s project in the Horner lab is particularly exciting because drawing a fuller picture of the RIG-I pathway would help us better understand how the innate immune system responds to an invasion of RNA viruses.  Lauren dived into a lot of the molecular biology details and did an amazing job of explaining her experimental design. More specifically, She’s testing whether 14-3-3e binds to the LIR motifs of RIG-I. Her project involves making plasmids that contain mutated versions of RIG-I, transfecting a RIG-I KO cell line with the plasmids, and seeing if there are changes in binding and downstream functions. After covering the relevant background information and giving an overview of the project, Lauren discussed the specific lab techniques she will be using, such as western blot and co-ip. Lauren not only demonstrated a great depth of knowledge of the system she’s studying but also gave a great explanation of the step-by-step approach of her methods. Studying pathways in the immune system has implications in infectious disease as well as rheumatology, and I look forward to seeing what Lauren will add to the important but incomplete map of the RIG-I pathway.

A morning in the lab usually starts with me going over past protocols and adjusting amounts/volumes of reagent based on experimental conditions and optimization guidelines. Most of what I have done during the past weeks was subcloning plasmids that had been designed during the first week. Depending on where I am in the process, a day in the lab could be filled with procedures like enzyme digestion, purification, ligation, or transformation. When I wait for a reaction to run to completion, I would read about the immune system, Yersinia pestis, or some primary literature that connects the two. I would also have time to discuss the scientific background and questions with my mentor almost everyday. This is something I enjoy a lot because it allows me to see the bigger picture of the work I’m doing. In the afternoon, in addition to the things I mentioned above, I would also observe how my mentor does some of her experiments, and I would practice cell culture techniques that aren’t used in cloning. This is important because after I create the plasmid coding for the mutant proteins, I will need to transfect human cells and infect them with Yersinia pestis. Every Tuesday, I meet with my PI to go over results, troubleshoot, and discuss future steps. Also on Tuesdays, during lab meetings, I learn about the projects that other researchers in the lab are working on.

What I particularly enjoy about doing research during the summer is that the science is the only thing I worry about. Doing research during the school year means that I would need to set up an experiment, go to class, and then run back to the lab to end the reaction and set up for the next step. The process is very hectic. As my PI told me when I first joined the lab, “science is better when you have time to think about it”. I’ve frequently found myself coming up with ideas while taking walks during lunch breaks.

My mentor is Rachel Keener. She is a third-year Ph.D. student in the Ko lab in the MGM department. She went to the University of Georgia and majored in genetics. Her first interest in biology, particularly genetics, stemmed from her ninth-grade biology class, in which she learned about genetic diseases. She found it fascinating how one amino acid change/deletion can make someone so sick, yet people can have a whole extra chromosome and still be relatively healthy. Her interest in this field grew further when she took ap bio a few years later and learned about the impact of epigenetics and microorganisms on human health. By then, she had decided to pursue scientific research as a career. What she likes most about science is that she gets to be involved in the process of answering questions she’s curious about. Rachel especially likes studying the intersection between infectious disease and genetics. She has always loved genetics because it’s like problem-solving for her. She likes infectious diseases because it’s easy to see a direct impact by treating them. 

At the same time, Rachel also developed an interest in science policy and global health. She grew up in Atlanta, GA, where the CDC is headquartered. Her future goal is to work in an organization like the CDC, where she would mostly work on cases. She is enthusiastic about communicating science and contributing to policy-making, so she envisions her future career to be 60% research and 40% policy and communication. Her favorite part of the day-to-day as a scientist is the flexible nature of the work — she gets to manage her own time and project. 

The Ko lab studies how genotypic variations contribute to the severity of infectious diseases. By infecting almost a thousand different cell lines, the lab has identified a single-nucleotide polymorphism (SNP) associated with variations in infection phenotypes by Yersinia pestis, the causative agent of the bubonic plague. The SNP is on a gene that codes for a transmembrane immunoreceptor. My mentor Rachel’s project focuses on the specific interactions between Y. pestis and the protein product of this gene. One way of confirming the role of the protein in bacterial invasion is to see if the clustering of this protein around Y. pestis changes for cells overexpressing mutated versions of this gene. The extracellular portion of this protein contains several immunoglobulin (Ig)-like domains. Based on the preliminary data from an experiment comparing all proteins in the same family as the protein of interest, Rachel suspects that Ig-like domains 1, 2, and 3 affect bacterial attachment. 

My project for the summer is to help design and build mutants that exclude each of the three domains. Infection of cells expressing the mutants can then show whether and how these Ig-like domains affect bacterial attachment and invasion. To accomplish this goal, I’ll first remove the DNA sequence coding for Ig-like domains 1, 2, and 3 from a plasmid that codes for the protein of interest. I’ll then ligate, separately, three mutated DNA fragments into the plasmid. HeLa cells transfected with the new plasmids will then express the mutated versions. Finally, infecting these HeLa cells with Y.pestis will reveal the critical domains for bacterial ligand binding. This project will contribute to the overarching goal of understanding how Y. pestis utilizes this protein to accomplish cellular invasion and how different genotypes of the protein affect Y. pestis infection.

Ever since I started learning about molecular biology, I’ve found the approaches in this field interestingly creative. What always amazes me is how scientists were able to find elegant ways of quantifying and measuring big questions from different angles. In addition to learning about the science and the lab techniques, I expect to practice something that’s perhaps more essential — how to think and tackle problems like a researcher. 

An advantage of doing research during the summer is that I actually have time to slow down and just think. One thing I learned during the short time I’ve been in the lab is that a big part of research is planning. This includes asking questions, thinking of ways to operationalize those questions, and designing specific experiments that address different parts of a question. My mentor Rachel’s research is about the interaction between Yersinia pestis (aka the plague) and a transmembrane protein. For the summer, my goal is to help design and study mutants of that transmembrane protein and see how different domains of its extracellular portion contribute to its binding with Y. pestis. There’s a lot of preparation behind every experiment. During the past week, we’ve mostly just been planning for an experiment. To design the ideal protein mutants for the project, we had to first look through literature and see how people have mutated this kind of extracellular domain to study them on other proteins. After that, we had to design several plasmids that express mutated versions of the protein of interest. A lot of effort has gone into just the logistics and designing. I think this is a fun part of research because it involves a lot of brainstorming and discussion. It also makes me even more excited about carrying out the actual experiment next week, as I have a much deeper understanding of the experiment’s proximate and ultimate goals.

I’ve always found biology fascinating, and I’m sure what I do in the future will have something to do with this giant field of biomedical sciences. Therefore, another important goal for the summer, then, is to figure out whether doing basic science research in the academic setting is what I want. So far, I’ve really enjoyed my time at the lab.