Meet Jenny Jiou
Major: Chemistry, B.S.
Graduation Year: May 2016 Field of Study: Biophysics Abstract: With No Lysine(K) kinase 1 (WNK1) and its isoforms lead a short cascade that regulate cation-chloride cotransporters, and WNK1 overexpresses in the kidney to control salt reabsorption and ultimately blood pressure. Previously, the Goldsmith lab determined the inactive structure of WNK1 and proved WNK1 as a chloride sensor through x-ray crystallography and biophysical analysis. Crystals of WNK1 with a nonhydrolysable ATP analog (AMP-PNP) have been obtained, and the crystal structure WNK1-KD/S378/S382* has been determined. This new conformer gives more insight on how the kinase domain works molecularly and mechanistically. Understanding the mechanism becomes quite important because many diseases stem from mutated kinases. In this case, the WNKs are linked to the familial form of hypertension and cancers, such as glioma. Ultimately, we strive to cocrystallized inhibitors from the UTSW High Throughput Screens with the protein to understand how drug binding works to further drug design rationale |
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My Experience:
My research experience there can be described in one word. Transformative. When Green Fellows started, I was going through my mid-college life crisis, still flopping between the practical choice of medical school and the interest of graduate school. My first project started off with crystallizing WNK1, learning the techniques and the basis of nucleation. My mentor provided me a map and model of an unsolved protein structure to practice with. This structure really started it all for me. I was hooked. I started dreaming about how each amino acid would fit into the density in a certain trouble spot I was working on. Then I modified the model with what I saw in my dream. Dr. Goldsmith checked over that segment, smiled, and approved of it, which doesn’t happen often for this seasoned protein crystallographer. This was only the beginning. |
These dreams occurred more frequently; giving me ideas for a new project I started on my own. Dr. Goldsmith could not have been more proud. I began to probe the mechanism of autophorylation by making mutations on WNK3 at certain points of interest. Then proceeded by running assays to determine the differences between the wild type and the mutants. I also obtained very beautiful crystals of WNK1 that diffracted to 2.0 Å at the synchrotron. With this high-resolution diffraction pattern, I solved my first structure in the middle beginning of June. This structure gave insight to an intermediate conformer. Currently, I’m still working with understanding the mechanism of autophosphorylation. I also hope to crystalize an active WNK1 and my WNK3 mutant to understand where the structure plays in this mechanism.
Sure there were ups and downs in the lab, but the final result is what drives me to keep on going. Every bit of data accumulated satisfies my curiosity but also makes me hungry for more answers. This research experience helped me feel more confident in my abilities to think on my own and survive in graduate school. I am planning to apply for the top Biophysics programs in the US, and the Green Fellowship will help me get there.
My Advice:
My advice is to immerse yourself in the papers your lab has published that pertains to your future projects during winter break. Contact your PI either by phone or in person before the Green Fellowship because they will give tips in what kind of work you’d be performing in the lab. Also, I know from experience reading literature maybe overwhelming at first, but it will click one day. It took me a little over a month to adjust and start thinking on my own, but I promise you that your efforts will be rewarded. Within the 9 months of working in the Goldsmith lab, I have a co-authorship and a first authorship under my belt, and this is not the end for me. Lastly, do not be afraid to ask questions and speak your mind. A lot of you will be intimidated by your lab, especially your PI, but just know this is a learning process. They will be your support systems throughout your Green Fellow journey, so it will be worth your while to get to know them |