Impostorism: What does it mean?
The time I had with the Fred Hutch program was great. Despite not being able to perform in-person experiments and interact with my peers face-to-face, the Fred Hutch Virtual Explorers in Cancer Research program gave strong insight on the inner workings of the cell cycle and immune system, the processes of cancer development in the body, the hallmarks of cancer, and the discussion of the ethics of vaccine distribution based on various global disparities. However, the lesson that really stuck to me the most was the lesson on the Imposter Syndrome by Alicia Morales.
Fear that I might not be good enough. Endless questions of who my success should be attributed to rather than my own hard work. Anxiety that others would believe I really am not that competent. These are all factors correlated with the Imposter Syndrome.
The Imposter Syndrome is a psychological belief that one is overrated and fraudulent and undeserving of the position they hold despite tangible proof that shows that he or she is qualified. When hearing Mrs. Morales talk about the symptoms and tendencies of how people who have the Imposter Syndrome feel, think, and act, all of what she said resonated to me on an interpersonal level. There were definitely times where I felt exactly like how others with the Imposter Syndrome felt.
Furthermore, to confirm my belief that I was, in fact, affected by the Imposter Syndrome, we were given the Clance's Imposter Phenomenon Test, which was a short 20 question quiz that asks for the answer that indicates how true the statement given is to your life. When I took this test, some of the statements appalled to me how true they were. Such statements like “I sometimes think I obtained my present position or gained my present success because I happened to be in the right place at the right time or knew the right people”, “at times, I feel my success has been due to some kind of luck”, and “I'm disappointed at times in my present accomplishments and think I should have accomplished much more”, were some of the psychological thoughts that come up quite often when I do something successful or when I reflect upon something I did successful. My score was a 72, which indicates that I have “significant Impostorism” which ranges from 61-80.
The reason this lesson stood out to me so much was the fact that the lesson was able to publicize what my true feelings were. I never knew what the psychology of feeling like your successes were from luck was actually called, and I thought they were very few who experience it. However, the fact that nearly 74% of the Fred Hutch VECR cohort experienced severe to intense Impostor Phenomena was astounding, and it made me feel less excluded.
XKCD.com
“What happens if the coronavirus’s spikes mutate?”
From the Fred Hutch website, I read an article that talked about whether mutations to the receptor-binding domain (RBD) will affect its ability to bind with the ACE2 molecule in human cells.
The coronavirus has a certain spike protein that serves as a "lock pick" in that the RBD of the spike binds to the ACE2 and inputs the virus inside that cell. The scientists at Fred Hutchinson Cancer Research Center wanted to delve deep into understanding how mutations to the RBD would affect the virus's ability to bind to ACE2. In the team's experiment, most of the mutations to the RBDs negatively affected the virus's binding ability to ACE2. However, there were quite a few mutations that helped the virus bind to the ACE2 more tightly. These results allow for the scientists to be able to attribute the diversity in these experiments to the accumulated evolution of these types of viruses and potentially how it could evolve in the future.
This study’s purpose and importance is multifaceted: not only does it provide work that is important to understanding the virus's evolution and understanding whether it can evolve to evade immunity in the future, but the study’s focus on understanding how mutations can affect the RBD can help guide the development of vaccines, since all vaccines in creation include the RBD to trigger immune response against viruses.
However, how can the study of specifically RBD mutations lead to improved vaccine design? The researchers used the technique called "deep mutational scanning" which catalogues every possible mutation to get a wider scope for RBD mutations. The data from this technique can be compiled into heat maps and visualizations, which shows how the mutations affected the RBD's form and function. In fact, the maps have the ability to identify the most stable forms of the protein that could be mass produced for COVID-19 vaccines that rely on the RBD. Hence, it saves time and money as well as creating more effective vaccines, especially the development of treatments that target certain parts of the RBD.
This image is one of the heat maps that was used to catalogue the scope of various RBD mutations through “deep mutation scanning”.
I spoke to Dr. Tyler Starr, the lead researcher of the study, about the specifics of the cataloguing.
He clarified that in the top heat map with red and blue boxes, that is the main indicator of showing the effect of mutations on RBD binding with ACE2.
The table shows columns, which are individual sites in the RBD where the amino acid side chains form contacts with ACE2. Each row of this table is one of the 20 possible amino acids, represented by their standard one-letter codes. The effect of introducing a given amino acid at a given RBD site, then, is represented by the color gradient, with red reflecting amino acid changes that make the RBD bind ACE2 more poorly, white showing that amino acid changes have minimal effect on function, and blue reflecting mutations that strengthen the interaction with ACE2.
For instance, the dark red boxes in the column for site 502 indicate that every amino acid mutation at that position strongly decreases the strength of binding for ACE2. Comparatively, site 501 have many of the amino acids marked as white or blue.
In doing both the scanning and the heat maps and visualizations, the procedures can further help guide efforts to mitigating the spread of COVID-19 with the creation of more successful vaccines. However, it is important to consider that the article concedes that their data leaves a lot of questions unanswered and should be further interpreted by the scientific community.
For instance, patients who have recovered from the COVID-19 naturally produce neutralizing antibodies that target the RBD, and a stronger understanding to how these antibodies can bind to the virus’s RBD is important to creating an effective vaccine. The scientists also don’t know whether these antibodies are strong enough to prevent the coronavirus from evolving and worsening in the future.
I initially chose this study to learn more about the inner-workings of how the COVID-19 works. What I learned was far from what I anticipated: I learned that vaccines in response to the COVID-19 are focused on the receptor-binding domain and the COVID-19 shares its spread through connecting their RBD to the ACE2. Also, he studies of evaluating the virus’s evolution and potential evolution gives me insight into the many factors and possibilities that goes into developing vaccines for viruses.
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