Meet Brendan Schmidt
Major: Biology and Microbiology, Double Major Graduation Year: 2018 Field of Study: Immunology Abstract: Aicardi-Goutierres Syndrome (AGS) is an autoimmune disease that is diagnosable in birth or early infancy. On a molecular basis, AGS is characterized by mutations in the genes encoding Three-Prime Repair Exonuclease 1 (TREX1), SAM and HD Domain 1 (SAMHD1), Adenosine Deaminase Acting on RNA 1 (ADAR1), Melanoma Differentiation-Associated Protein 5 (MDA5) –which is encoded by IFIH1-, and all three subunits of Ribonuclease H2 (RNASEH2). TREX1, RNASEH2 and SAMHD1 are believed to convey preventative measures against the type I interferon response by preventing the activation of the cGAS-STING pathway. In AGS patients, these mutations impair the function of the translated protein. This loss of function causes a vast overexpression of immunostimulatory genes (ISGs) which results in chronic inflammation and cell death. Malfunctions in the cGAS-STING pathway are implicated in cancer due to the chronic inflammation that is produced. This inflammation is believed to attract macrophages and induce apoptosis, naturally targeting malfunctioning cells. In our work, we examine the role of the proteins implicated in AGS (TREX1, SAMHD1, and RNASEH2A – the catalytic component of RNASEH2) as well as a protein directly implicated in the interferon response – Stimulator of Interferon Genes (STING) – in cancer migration and proliferation. Two types of murine cancer cells – B16 (melanoma) and E0771 (carcinoma) – are used for all assays. We determined the baseline gene expression of TREX1, SAMHD1, RNASEH2A, and STING in both cell lines using qPCR as well as metastasis ability through scratch-wound healing assays before and after knockdown. |
In most subject areas of research, your work will generate a lot of negative data and then eventually some positive data that supports what you were trying to test.
|
My Experience:
I think the Green Fellows program is a great program regardless of if you're pre-MD, pre-MD/PhD, or pre-PhD. With that being said, I think there are a few potentially negative things to note about the program. 1) If you have worked at a lab at UT Dallas, you may be used to the short walk to lab and being able to return to on-campus housing while you wait for your experiments to complete. At UT Southwestern, this isn't an option. There's normally a lot of waiting time where there's almost nothing for you to do. 2) The commute is pretty long if you take it during or near rush hour. The commute to UT Southwestern, without traffic, is about 30 minutes, but it took me almost two hours once when I had the great idea to leave the campus at 4:30pm. 3) The research is likely to become monotonous after the first month or month and a half. Most research is rinse-and-repeat. Remember that you're going to be there in the lab for 100% of that, something you may not be used to in a UTD lab where you work part-time. There are, however, many, many upsides to the program - more than I care to list. I cannot speak for the other Greens, but I was placed on a new R01 project - a giant NIH project typically left for graduate students to do their dissertations with - and got to helm the project alongside my graduate mentor. In this capacity, I was able to develop new protocols for the lab based on literature and perform some experiments that nobody in the lab had done before. That's a pretty neat feeling when you look at the work you're doing and think "I wrote this protocol and now the lab is going to use it after I'm gone." I should point out, though, that I've decided, definitively, that I abhor immunology. I wouldn't be caught dead working in another immunology lab. In most subject areas of research, your work will generate a lot of negative data and then eventually some positive data that supports what you were trying to test. Not immunology. Immunology simply decides to not work 90% of the time. Experiments fail back to back to back when they worked just fine last month. You don't generate negative data. You just simply don't generate anything. It's not "I learned 101 ways not to make a lightbulb" in immunology. Immunology is more like "I have the schematic for the lightbulb but none of this crap will go together even though the schematic tells me it does." This was kind of rough for me. I went more than a month trying to get shRNA to work in my cancer cell lines. After heavy selection and four attempts, we gave up and went to siRNA. Funny enough, this exact same shRNA worked a few months ago in non-cancer cells of the same type, and it worked incredibly well. We even ordered new shRNA with the same sequences in case the old shRNA had gone bad. And the siRNA? That worked great the first time, but it barely worked the second time, didn't work the third time, and killed all of our cells the fourth and fifth times. After Green, I still haven't cast away the possibility of applying to MD/PhD programs, but I've certainly decided that, if I do an MD/PhD, I won't be doing any work in an immunology lab. |
My Advice:
Try new things! You get one shot to work on the UT Southwestern campus as an undergraduate. Use that opportunity to get out of your comfort zone scientifically speaking. Work in a lab that has no relation to what you've done in the past but think you may have an interest in. Utilize the people on the campus - if you're planning to apply to graduate school, make sure Dr. Street knows you; if you're planning to apply to medical school, make sure to set up a metting with Anne McLane, the director of admissions to the medical school. You have one shot at being a Green Fellow. Make sure you get the most out of it. |
...get out of your comfort zone scientifically speaking. Work in a lab that has no relation to what you've done in the past but think you may have an interest in.
|