Meet Tra Ngo
Major: Molecular Biology and Mathematics - Double Major
Graduation Year: December 2017
Field of Study: Molecular Biology
Spinal Muscular Atrophy (SMA) – an autosomal recessive neurodegenerative disease of motor neurons, is a leading genetic cause of infant mortality and results from homozygous loss of function of the Survival of Motor Neuron 1 (SMN1) gene. In humans, a nearly identical copy of SMN1 known as SMN2 can generate full-length functional SMN protein that can compensate for loss of SMN1. However, a single C to T difference in SMN2 causes skipping of exon 7 during splicing, generating the predominantly unstable protein SMN7 and very limited amounts of full-length functional protein. As such, understanding the mechanisms that regulate the splicing of exon 7 in SMN2 pre-mRNA could lead to the development of new therapeutic strategies that increase the amount of functional protein produced from the SMN2 gene. Previously, pre-mRNA splicing of SMN2 has been studied in the context of a minigene construct that does not fully recapitulate regulation of the endogenous gene. Using CRISPR/Cas9, we generated a cell line harboring a Green Fluorescent Protein (GFP) open reading frame integrated at the endogenous SMN2 locus that expresses GFP only when exon 7 is included in the mature mRNA. This new reporter cell line will facilitate future studies, including genome-wide screens, to interrogate mechanisms that regulate SMN2 splicing.
Before the Green Fellowship, I had had various research experiences, mostly in topics in mathematics and computational applications in biology. Entering the Mendell Lab, I was extremely excited to the challenge of working in an unfamiliar area. I learned deeply not only about my research subject but also about the current status of the post-transcriptional regulation field, through other projects and discussion in the lab. The lab was bigger than any that I had been in; and through great effort trying to adapt to this new environment, I learned a lot on how to conduct myself. My research project was stably progressing forwards with enough local maxima and minima to keep me interested and motivated.
At UTSW, outside of the lab, there were many fascinating talks, informative seminars, and inspiring lunchtime conversations that comprise the wonderful experience that Green Fellows Program offered. As a whole, the Green Fellowship at UTSW experience definitely matured my scientific thinking and professional manner.
Your five months of work may not yield any significant discoveries. But do not be discouraged. There is always some degree of uncertainty in scientific research. Embrace it!
Do not expect everything to work perfectly. Your experiments may fail. You may have to redo them multiple times or come up with different approaches. Your five months of work may not yield any significant discoveries. But do not be discouraged. There is always some degree of uncertainty in scientific research. Embrace it! Because those hardwork and times spent in the fog trying to find the light are what make the truth worth and the moment of discovery joyous. Just remember to tread carefully and think before you step. Tell your mentor your ideas. Better yet, if it is ok, discuss your science with your colleagues -- postdoc, graduate students, maybe even other Green Fellows. I cannot expect the other lab members to be my best friends, but I can certainly talk science with them.
There would most likely be time that things do not work and you feel frustrated. Try to lift your spirit up. Find happiness in the simple things. Your experiment did not work, but you poured a handsome gel. Good job! Be happy. And get ready to try again to improve your results. Go to seminars. The spring semester has many lectures by researchers all over the world, which can be found at http://www.utsouthwestern.edu/life-at/events/index.html. Get stuck? Take a break and attend the seminars. They may inspire you of a solution!
Many must have told you to not be afraid to ask questions. I agree. Let me add a bit of spice to that: do your homework before you ask. Respect other people's time and do a bit of thinking beforehand. You may even come up with a better question that would stem for an interesting story.
Read variously, relevantly, and vigorously.
Finally, write down your own thoughts, learning, and experiences along the way. You will certainly find valuable self-revelations towards the end of the fellowship. (And you will certainly be asked to give advice for subsequent generations of Green Fellows!)