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When Yeongseo Son was initially invited to join the <\/span>Spranger Lab<\/span><\/a> as part of the<\/span> Bernard S. and Sophie G. Gould MIT Research Program in Biology<\/span><\/a>, she thought the email was spam. Having grown up in the South for most of her life, she had never pictured herself at MIT.<\/span><\/p>\r\n\r\n\r\n\r\n Back home at the University of Georgia, Son studies neutrophils, a kind of innate immune cell that serves as the body\u2019s first line of defense against foreign pathogens. After taking a graduate-level course on immunology last semester, Son realized she needed to increase her basic understanding of the broad discipline.<\/span><\/p>\r\n\r\n\r\n\r\n \u201cI knew that coming to work with Professor Spranger would give me a chance to work on cancer immunology and T cell biology, two really cool and important fields I haven\u2019t been exposed to,\u201d Son says.<\/span><\/p>\r\n\r\n\r\n\r\n It took several attempts from the Senior Lecturer and BSG-MSRP-Bio program coordinator Mandana Sassanfar to reach her before Son accepted. <\/span>\u00a0<\/span><\/p>\r\n\r\n\r\n\r\n \u201cBefore I arrived, I was worried it would be too intense or that I wouldn\u2019t fit in,\u201d Son says. \u201cI couldn\u2019t have been more wrong: yes, the work is challenging, but everyone is here because they truly love science.\u201d<\/span><\/p>\r\n\r\n\r\n\r\n In the lab of <\/span>Stefani Spranger, Associate Professor in the Department of Biology and Intramural Faculty of the Koch Institute for Integrative Cancer Research,<\/span><\/a>\u00a0Son was first tasked with a seemingly simple second project: growing a new strain of influenza to infect mice that had recently recovered from another strain.\u00a0<\/span><\/p>\r\n\r\n\r\n\r\n This quest involved multiple steps, such as culturing cells, infecting the cells with the virus, and measuring how lethal it is to host cells, working with a strain that her lab hadn\u2019t used before.\u00a0\u00a0\u00a0<\/span><\/p>\r\n\r\n\r\n\r\n To test the strength of the virus, the virus is mixed with host cells in order to infect them. Then the host cells are placed on a layer of agar, a gelatinous substance that provides nutrients for the host cells.<\/span> When a virus-infected cell dies, it creates a hole in the layer of cells called a plaque. The number of plaques is recorded to determine the virus’s titer, or frequency.\u00a0<\/span><\/p>\r\n\r\n\r\n\r\n Son excitedly executed her plaque assay after breezing through the first two steps. The next day, to her surprise and disappointment, all her cells \u2014 including the negative control \u2014 had died.\u00a0<\/span><\/p>\r\n\r\n\r\n\r\n \u201cThe first time it failed, I was crushed because I had written the protocol over and over,\u201d Son says.\u00a0<\/span><\/p>\r\n\r\n\r\n\r\n That initial disappointment, however, turned into excitement to solve the problem. She worked closely with her mentor, Postdoc Taylor Heim, who helped motivate her to keep trying to figure out what had gone wrong.<\/span><\/p>\r\n\r\n\r\n\r\n Son spent weeks designing a process to effectively titer the virus. She laid out a plan of action to assess what could be toxic to the cells and systematically tested each component of the protocol that could affect the growth of her strain of influenza.\u00a0<\/span><\/p>\r\n\r\n\r\n\r\n It took Son four attempts before she had a eureka moment: the success of her cell cultures depended on the precise measurement of just one reagent.\u00a0<\/span><\/p>\r\n\r\n\r\n\r\n Too much of the reagent meant the cells would all die on arrival, but just a little bit, and they would survive. It took Son three more attempts \u2014 seven experiments in total \u2014 to fully ensure the success of the assay.<\/span><\/p>\r\n\r\n\r\n\r\n Throughout this process, and despite her many failures, Son realized she finds troubleshooting very enjoyable. Each failure was unique and crucial for her eventual success.\u00a0<\/span>\u00a0<\/span><\/p>\r\n\r\n\r\n\r\n \u201cI\u2019m making a difference \u2014 I\u2019m figuring something out that can really help with future experiments,\u201d Son says. \u201cThat moment of success is why I gained such confidence in being a scientist.\u201d<\/span><\/p>\r\n\r\n\r\n\r\n In the Spranger Lab, Son\u2019s other summer project focused on the respiratory system. She was examining a type of specialized cell called resident memory CD8+ T cells in the lungs and lymph nodes of mice infected with influenza. These specialized T cells gain a kind of memory of how to fight off a virus and remain in the lungs and lung-draining lymph node tissues long after the tissues have overcome the immune challenge of something like influenza.\u00a0<\/span><\/p>\r\n\r\n\r\n\r\n Son\u2019s postdoctoral student mentor Taylor Heim is especially interested in the potential of these cells for cancer immunotherapy.<\/span><\/p>\r\n\r\n\r\n\r\n To better understand how the resident memory T cell populations change over time, Son and Heim conducted a time-point experiment in which mice were studied at different points after being infected with influenza. They do this by injecting antibodies into the mouse\u2019s bloodstream after infection, which mark any immune cells circulating in the blood, allowing the researchers to gauge if the cells are recruited to help fight a virus.<\/span><\/p>\r\n\r\n\r\n\r\n Son\u2019s work this summer goes deeper, examining proteins known as cytokines that enable the immune system to combat germs or other substances that can harm an organism.\u00a0<\/span><\/p>\r\n\r\n\r\n\r\n Son used a genetically modified mouse to track the production of interferon-gamma, IFN\u2010\u03b3. IFN\u2010\u03b3 is a cytokine that plays a key role in regulating immune responses, often helping fight off infection and cancer. Son found evidence that resident memory T cells produce this cytokine in both the lungs and lung-draining lymph nodes.\u00a0<\/span><\/p>\r\n\r\n\r\n\r\n The goal of this research is to one day use the information collected on resident memory CD8+ T cell populations and cytokine expression to help systematically target cancerous cells that appear in the body.<\/span><\/p>\r\n\r\n\r\n\r\n \u201cYeongseo has <\/span>helped us pioneer a system to track how these cells move within tissues of living mice,\u201d Spranger explains. \u201cBy using this approach, we will be able to understand how they are affecting cancer development and how cancer is affecting them, and that\u2019s pretty exciting.\u201d<\/span><\/p>\r\n\r\n\r\n\r\n The BSG-MSRP-Bio program also gave Son near-constant access to faculty from across the biology department, both through extracurricular offerings such as dinner seminars and journal clubs as well as departmental retreats.\u00a0<\/span><\/p>\r\n\r\n\r\n\r\n She\u2019s also sat down with professors individually and heard more about their stories and research as part of her podcast <\/span>Let\u2019s Talk Chemistry<\/span><\/i><\/a>. Nobel Laureate <\/span>Phil Sharp<\/span><\/a>, whose office is on the same floor as the Spranger Lab, joined the show after Son dropped by his office to introduce herself. Son learned more about his discoveries in RNA splicing and the behind-the-scenes details of his Nobel Prize ceremonies.\u00a0<\/span><\/p>\r\n\r\n\r\n\r\nVexing Viruses<\/b><\/h2>\r\n\r\n\r\n\r\n
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\r\nLighting Up the Lungs<\/h2>\r\n\r\n\r\n\r\n
Learning Outside the Lab<\/h2>\r\n\r\n\r\n\r\n