Majors: Biological Sciences and Mathematics
“Simulated and Experimental Effects of RNA Interference on Cell Motility”
Cell migration is a critical and recurrent phenomenon in animal biology; migration is a key feature in wound healing, immune function, and embryo development. In particular, egg chamber developmental stages in Drosophila melanogaster, a model organism for human genetics, provide a suitable opportunity to investigate migratory regulation. An important process in oogenesis is when the epithelial border cells on the anterior end of the egg chamber move toward the oocyte. A key molecular pathway in this process involves the uptake of the ligand Unpaired by follicle cells, which causes the signaling molecule Signal Transducer and Activator of Transcription (STAT) to activate transcription of downstream targets that promote migration. In genetic analyses of D. melanogaster ovaries that had reduced STAT expression via RNA interference (RNAi), we reproduced phenotypes of partially delayed or completely inhibited migratory behaviors compared to sibling controls. To investigate this phenomenon mathematically, we used a previously derived system of differential equations that modeled the signaling pathway, reduced the system with simplifying assumptions, and introduced a parameter to account for the effect of RNAi on mRNA that encoded STAT. Through computational methods, we simulated time courses of select proteins and created a bifurcation diagram of their steady states. Moving forward, research into this process could examine the biological bases for temporal variation in RNAi-based effects on protein expression as predicted in our mathematical models. This research will help biologists obtain a better understanding of mechanisms for cell migration, which may itself lead to insights on migratory pathways for the metastasis of cancer and the occurrence of other developmental defects.
This work was funded in part through an Undergraduate Biology Mathematics (UBM) Research Award from the National Science Foundation under Grant No. DBI 1031420, PIs Drs. Leips and Neerchal.
What research have you been doing this summer?
This summer I work with Interdisciplinary Training for Undergraduates in Biological and Mathematical Sciences (UBM). The program pairs a biology student with a mathematics student to work at the intersection of the two disciplines for two years.
We study the underlying mechanisms of cell migration through experiments and simulations. Cell motility is a key aspect in animal biology because many processes (such as wound healing) involve cell migration, and the failure to migrate or inappropriate migration can lead to disease (such as developmental defects or the metastasis of cancer). Fruit flies provide a good model organism because many genes and pathways have been conserved from the fly-human common ancestor to both modern day species. In particular, we look at border cell migration in stages 9 and 10 of fruit fly egg chamber development and computationally examine the biochemical pathway that signals border cells to migrate.
During the summer, we dissected fruit fly ovaries, witnessed migratory phenotypes through fluorescent microscopy, reduced a previous mathematical system that models this pathway to seven differential equations, and used MATLAB and XPP to understand the dynamics of the proteins and messenger RNA (mRNA) involved in the pathway through time course simulations and bifurcation diagrams. Future research during the school year will be to study more genotypes in novel ways, to use qrtPCR to quantify mRNA levels in the cells, to continue to use MATLAB to investigate our biochemical model, and to expand our bifurcation diagrams in XPP to three dimensions. We hope to publish a paper by the end of next year.
How did you find out about this opportunity?
In my freshman year, the program director for UBM spoke to the Biology Council of Majors about this research opportunity, and – in a later semester – I took a class with Dr. Peercy who works with the program. I talked to him after class, he said that he would look at the application that I submitted online, and a few weeks later he invited me for an interview with him and Dr. Starz-Gaiano.
Who did you work with on this project?
My research partner, Pranjal Singh, is a senior majoring in mathematics with minors in chemistry and quantitative biology. Pranjal and I worked in the Starz-Gaiano lab, working with graduate students Lathiena Manning, Amanda Monahan, and Afsoon Saadin; post-doc Dr. Neus Sanchez-Alberola; and fellow undergraduate Roxana Rodriguez-Stewart from the University of Puerto Rico. Dr. Michelle Starz-Gaiano (Assistant Professor in the Department of Biological Sciences) and Dr. Bradford Peercy (Assistant Professor in the Department of Mathematics and Statistics) are our immediate supervisors, and we also work with the UBM team as a whole in occasional meetings.
Was this your first independent research project?
This was my first research project of this scale (a two-year commitment), but I have performed research in prior positions in government, academia, medicine, and journalism. These include an internship with the Protein Chemistry Lab at the National Institutes of Health, another with the Lin lab at UMBC (studying the olfactory systems of mice), a program at Meritus Medical Hospital where I shadowed and interned for a cosmetic surgeon, and an editorship position with the UMBC Review: Journal of Undergraduate Research. Through past experiences, I gained experimental, computational, speaking, and writing skills that prepared me well for this project, just as I hope that this project will prepare me well for my future career.
Do you get course credit for this work or get paid?
I receive PRAC 098, BIOL 499, and BIOL 499L credit for this work. I am paid for ten weeks of full-time summer work and $8 hourly during the academic years. UBM offers an additional stipend for living expenses and provides us with free housing over the summer.
How much time do you put into it?
During the academic year, it can vary from two to 10 hours per week, depending on coursework and how much research we are doing at that point. Over the summer, I worked 35 hours per week, and I spent a full week in Columbus, OH for an undergraduate capstone conference with the Mathematical Biosciences Institute.
What academic background did you have before you started?
My academic background luckily is diverse in the sciences, which prepared me for this interdisciplinary research. My rudimentary computer science background proved crucial in being able to use MATLAB for this research, my knowledge from my genetics and cell biology courses were pivotal for me to grasp the concepts, and recently taking Partial Differential Equations and Biomathematics with Dr. Peercy helped me to know how to use mathematical modeling to understand biological phenomena. While those topics cover the bulk of knowledge necessary for this biomathematical research, even key concepts in chemistry and physics turned out to be handy, and my motto is that you can never learn too much.
How did you learn what you needed to know to be successful in this summer project?
Reading past literature, using an online database of fruit fly information, and asking lots of questions were the main ways in which I learned how to be successful in my research.
What was the most unexpected thing?
I did not realize how much I would love developmental and cell biology. When I began, I thought that I would enjoy the techniques (the experiments, the computations) more than I would enjoy the topic. The cellular level of biology used to confuse me and seem too riddled with exceptions for me to appreciate fully. Now that I understand many of the processes going on, how researchers discover those processes, and what it looks like to capture them both experimentally and mathematically, I truly enjoy working on the cellular level and find it amazing that similar processes are happening around (or inside) us all of the time. Cell research is groovy!
What is your advice to other students about getting involved in research?
Start early, talk to your professors, apply to a variety of research opportunities (not just the prestigious ones!), work hard, aspire to long-term goals (publishing a paper, attending a conference), make connections, and have fun. For early interns, this is the time to figure out what you like; for more accomplished interns, this is the time to build your career with a sturdy foundation. Find people that you enjoy and research that you love.
What are your career goals?
My career goal is to become a professional researcher in either a biological or medical field. I will pursue a doctorate degree, and then I hope to attain a teaching position at a university or medical school. Some topics that intrigue me are neuroscience, immunology, epidemiology, and genetics, and perhaps one of those will eventually become my main focus. I hope to incorporate mathematical or computational components into whatever research I eventually pursue as a profession. (Math is also groovy!)
What else are you involved in on campus?
I am an Honors College scholar who is heavily involved with the Honors College Council as well as in Honors Forum through a teaching position. I have been a member of many student organizations over the years (namely Astronomy, Linguistics, and Rocketry Clubs), and upon graduation I will have served on the executive board of the Biology Council of Majors for 3.5 years. I am also a member of the National Society of Collegiate Scholars and Pi Mu Epsilon (a national honor society for mathematics). Through these involvements, I have met and felt part of amazing communities as well as assisted those communities (such as through organizing events or improving logistics).