BIOL368/F20:Class Journal Week 6

Yaniv Maddahi Response

1. In addition to the scientific conclusion for your project, reflect on what you learned as a person by performing this research. Describe what you learned with your head (scientific knowledge), hands (technical skills), and heart (personal or teamwork qualities needed to succeed as a scientist).
   • I learned a lot about the variations among different organisms and their ACE2 sites and the variations among the amino acids found in certain positions. Through that I was able to predict how the organisms interacted with each other. Through working in a team I understood the importance of communication and dividing work evenly to ensure optimum group work. I learned to search for my own data based on our own research question and used my experience with previous softwares to create my results. As stated earlier, I learned the importance of communication when working in a team and how it’s all a matter of moving parts that work together to create the bigger picture.
2. What is still not clear to you after having concluded this project?
   • I’m still curious as to whether there are more components than just a few amino acids that go into the interactions, such as any cofactors or coenzymes, that impact binding strength. I am mostly curious about this because the Wan paper mentioned civets playing a role in acting as a host organism but after reviewing the sequence we noticed that civets are reasonably different from humans in the amino acids it has in the 353 and 31 positions. Thus, I am curious what factors go into the binding even more.
3. If you had more time (anywhere from a few more weeks to a couple of years, like, for example, a Master's thesis project), what future directions would you like to take for this project? You will have the opportunity to conduct a second, more in-depth research project in the latter part of the semester.
   • I would want to possibly create models of all of the ACE2 proteins for the animals and test them and their binding. Even possibly if I had a lab to create samples and see the different rates of infection, spreading, etc. For the next project, perhaps creating models to see if we can visualize the different interactions between organisms and SARS-CoV2.

Yaniv Maddahi (talk) 15:24, 14 October 2020 (PDT)

Aiden Burnett's Response

1. In addition to the scientific conclusion for your project, reflect on what you learned as a person by performing this research. Describe what you learned with your head (scientific knowledge), hands (technical skills), and heart (personal or teamwork qualities needed to succeed as a scientist).
   • Head: I learned that the word "residue" is simply used to describe amino acids in polypeptide chains. This was used frequently in the Wan et al. paper to my confusion as I have not taken biochemistry.
   • Hands: I gained more experience with the iCnD3 protein visualizer, as well as Microsoft excel and Google sheets which were used to generate tables.
   • Heart: I had already worked well with my partner Anna Horvath in the past but this assignment required much more collaboration than the previous individual journal assignments. We were easily able to divide labor fairly and provide useful feedback to each other. Cordial collaboration is a skill which I already had but any chance to practice it is welcome.
2. What is still not clear to you after having concluded this project?
   • I suppose I am unsure of how identifying SARS-CoV-2's lineage and intermediate host is useful to us in combatting the pandemic. I see that it is still useful to know in terms of preventing outbreaks of other coronaviruses but as far as I know we are looking for the intermediate host in the hopes that it will reveal useful lines of research. If there is already a plan for how this could combat the pandemic I am unaware of it.
3. If you had more time (anywhere from a few more weeks to a couple of years, like, for example, a Master's thesis project), what future directions would you like to take for this project? You will have the opportunity to conduct a second, more in-depth research project in the latter part of the semester.
   • We identified that Orangutans and Grivet Monkeys have the most similar ACE2 receptors of possible intermediate hosts. This could inform a study looking to identify the lineage of SARS-CoV-2. This would involve comparing the sequences of coronaviruses from these, and other, species to SARS-CoV-2.

Aiden Burnett (talk) 22:02, 14 October 2020 (PDT)

Owen Dailey's Response

1. In addition to the scientific conclusion for your project, reflect on what you learned as a person by performing this research. Describe what you learned with your head (scientific knowledge), hands (technical skills), and heart (personal or teamwork qualities needed to succeed as a scientist).
   • Head: I learned about a really cool mutation in the SARS-CoV-2 spike sequence that has arisen and gained prevalence in the last 9 months.
   • Hands: I gained a lot of experience with analyzing the sequence alignment and being able to compare the results of the phylogenetic tree to it.
   • Heart: My research partner, Ian Wright, and I would work on out work independedntly and then come together and discuss our progress results every few days. I really liked this technique as it allowed us to pace ourselves and also discuss the results on a consistent basis.
2. What is still not clear to you after having concluded this project?
   • I am still unsure as to how the D614G mutation in the spike protein has resulted in a more “dominant” SARS-CoV-2 strain.
3. If you had more time (anywhere from a few more weeks to a couple of years, like, for example, a Master's thesis project), what future directions would you like to take for this project? You will have the opportunity to conduct a second, more in-depth research project in the latter part of the semester.
   • If I had a long time and the resources, I would try to uncover the method by which a D614G leads to a more prevalent SARS-CoV-2 strain.

Owen R. Dailey (talk) 19:26, 14 October 2020 (PDT)

Macie Duran

1. In addition to the scientific conclusion for your project, reflect on what you learned as a person by performing this research. Describe what you learned with your head (scientific knowledge), hands (technical skills), and heart (personal or teamwork qualities needed to succeed as a scientist).
   • I learned more about how the ACE2 receptor regularly functions in our bodies, and why it is so important. I was also able to learn more about how ACE2 varies in mammals, and how those variations connect with the way that SARS-CoV-2 recognizes and binds to ACE2. This project also got me a lot more interested in the development of COVID-19 vaccines and treatments that are occurring right now. I also became more skilled in using Phylogeny.fr, UniProt, NCBI GenBank, and the NCBI iCn3D structure database to conduct research of my own. Lastly, my partner and I were able to work together to efficiently complete our research on the ACE2 receptor. We were both able to complete our own work and then share with one another to come to our conclusion and consider future directions that could be taken.
2. What is still not clear to you after having concluded this project?
   • I would like to know more about how the ACE2 receptor can be targeted in treatments. While researching, I read a few articles that hypothesized that many of the symptoms of COVID-19 are due to the destruction of ACE2 receptors, and the impact that has on Angiotensin II levels. Of course I don’t have enough knowledge or skills to develop a treatment, but I would like to know if it would be possible to only target specific sequences of ACE2 receptors to disrupt the viral-binding hotspots without altering regular structure and function.
3. If you had more time (anywhere from a few more weeks to a couple of years, like, for example, a Master's thesis project), what future directions would you like to take for this project? You will have the opportunity to conduct a second, more in-depth research project in the latter part of the semester.
   • I would like to look into genetic variance in ACE2 within humans, and how that can impact its interaction with SARS-CoV-2. Are there certain key residues that can increase or decrease our susceptibility to the binding and entry of SARS-CoV-2?

(Macie Duran (talk) 20:29, 14 October 2020 (PDT))

Nathan Beshai

1. In addition to the scientific conclusion for your project, reflect on what you learned as a person by performing this research. Describe what you learned with your head (scientific knowledge), hands (technical skills), and heart (personal or teamwork qualities needed to succeed as a scientist).
   • I really enjoyed working with the 3-d proteins. This taught me a lot about protein structure, shape, and function. I wish this was employed in a general biology class so that students can learn about the folding and bonding of proteins while working with them. I also learned that viruses bind to receptors that function for a completely different purpose. The ACE2 protein is originally used in hypertension and blood clotting. This research also taught me how anybody can really study protein sequences and structure from home and for free. This is really cool because it shows that any aspiring scientist does not need the most expensive software or a huge lab but only access to a computer. I learned how to examine protein structures and was able to see stuff learned in other classes on an actual protein in the body. Lastly, my working with a partner allowed me to see how somebody looking at your work from a different perspective helps better the work and give another glance at it. My partner also taught me skills that I never knew and something I can take with me forward in different projects.
2. What is still not clear to you after having concluded this project?
   • Something that's still not clear for me is the type of bonding that the 2019-nCoV has with the ACE2. I was interested in the type of bonding because I wanted to know how strong the link is between them. Something that also confused me is how only 8 amino acids are necessary for the structure and function. A protein that has hundreds of amino acids, so I expected them all to be necessary for the structure and function.
3. If you had more time (anywhere from a few more weeks to a couple of years, like, for example, a Master's thesis project), what future directions would you like to take for this project? You will have the opportunity to conduct a second, more in-depth research project in the latter part of the semester.
   • In a lab, I would like to explore the ACE2 5 amino acid residues that bind to the 2019-nCoV spike protein structure. I would want to cause a mutation/s that causes the ACE2 to be completely incompatible with the virus and then test its structure and function. Since it is another research project from the computer I want to observe the bonding between the ACE2 of different species and the spike protein. This would allow finding a specific mutation that causes weaker bonding or no bonding.

Nathan R. Beshai (talk) 21:39, 14 October 2020 (PDT)

Anna Horvath

1. In addition to the scientific conclusion for your project, reflect on what you learned as a person by performing this research. Describe what you learned with your head (scientific knowledge), hands (technical skills), and heart (personal or teamwork qualities needed to succeed as a scientist).
   • Head: I learned about how to compare sequences to one another to find percent similarities. Previously, I had only worked with phylogenetic trees to compare sequences.
   • Hands: I gained more experience manipulating sequences, from the process of finding them, to creating an alignment, and analyzing this alignment in a fluent manner. I will be able to apply this to future research I will conduct.
   • Heart: I was able to work really efficiently with my partner Aiden Burnett. We had worked together well in the weeks prior, but we were able to complete this assignment in a very fluent manner together. I found that we worked very similarly and our styles of work complemented each other.
2. What is still not clear to you after having concluded this project?
   • I would like to know about how the ACE2 receptor can be used to develop potential vaccines. The ACE2 receptors we looked at were relatively conserved and I would like to know whether this knowledge could help us in the testing and development of such vaccines, as well as the identification of potential future intermediary hosts to viruses binding to ACE2.
3. If you had more time (anywhere from a few more weeks to a couple of years, like, for example, a Master's thesis project), what future directions would you like to take for this project? You will have the opportunity to conduct a second, more in-depth research project in the latter part of the semester.
   • I would like to look at other SARS viruses and observe their potential in binding to the different organisms we studied, more specifically in orangutans and monkeys, as they had the most similar receptors to humans.

Anna Horvath (talk) 21:45, 14 October 2020 (PDT)

Ian Wright

1. In addition to the scientific conclusion for your project, reflect on what you learned as a person by performing this research. Describe what you learned with your head (scientific knowledge), hands (technical skills), and heart (personal or teamwork qualities needed to succeed as a scientist).
   • I learned a lot about iCn3D with this project. I had to read through a lot of the help doc to figure out how to isolate a single protein subunit and then make edits to just this subunit. I also got really comfortable identifying domains using the 3d structure. After uncovering the D614G mutation, I was challenged to conduct some critical analysis toward the meaning of this mutation. It was really sweet seeing that this mutation was such a big deal in the research community. I learned a lot while working with Owen. We had a very clear and communicative dynamic that ended up working really well. We didn't double any efforts and the specialization we each had in our separate responsibilities provided some quality results. As for scientific knowledge, I'm really enjoying the amount of detail we can discover in analyzing specific amino acids. The analyses I read through to conduct my interaction figures gave me a deeper understanding for the meaning of a pinpointed mutation.
2. What is still not clear to you after having concluded this project?
   • Why the heck does our Indian strain have so many mutations?! Also, the concept of a dehydron backbone hydrogen bond is slightly confusing to me in how it interacts with solvent and how it facilitates the complexification of the S1/S2 subunits. These questions come from Fernandez 2020
3. If you had more time (anywhere from a few more weeks to a couple of years, like, for example, a Master's thesis project), what future directions would you like to take for this project? You will have the opportunity to conduct a second, more in-depth research project in the latter part of the semester.
   • What makes the Indian strain so mutable? Also, has the D614G mutation facilitated an increase in viral spread rate?

Ian R. Wright (talk) 23:06, 14 October 2020 (PDT)

Fatimah Alghanem

1. In addition to the scientific conclusion for your project, reflect on what you learned as a person by performing this research. Describe what you learned with your head (scientific knowledge), hands (technical skills), and heart (personal or teamwork qualities needed to succeed as a scientist).
   • personally this project taught me a lot about how to find data and make sense of it. Also, I learned how hard it is to actually obtain the data that a researcher needs. And working with my partner, I learned to communicate scientifically.
2. What is still not clear to you after having concluded this project?
   • it's not clear to me if there's an easy way to find a position in a sequence
3. If you had more time (anywhere from a few more weeks to a couple of years, like, for example, a Master's thesis project), what future directions would you like to take for this project? You will have the opportunity to conduct a second, more in-depth research project in the latter part of the semester.
   • I would look at much more sequences to see in-depth the difference between them.

Falghane (talk) 23:56, 14 October 2020 (PDT)

JT Correy

• I think that I learned a lot by completing this project. I certainly gained a significant amount of scientific knowledge. Prior to the past week the only biological/chemical understanding I had of COVID was from the Wan article, so this broaden my knowledge even more. I feel much more comfortable making models now. I struggled to make our 3D model but once I finally got it figured it sort of clicked and I think I could definitely do similar models. As a person I don’t think I really learned anything from this. While the topic was new for me, the process of presentation making is something I have done a lot.
• I think that there is still a massive amount of information regarding the Corona virus that I don’t understand. I do feel like I have a decent understanding of how it infiltrates cells at the chemical level. I would be interested to study the virus on a global scale and look at infection patterns and bigger aspects of the virus.
• I am very interested in the lingering effects of the virus. I have seen several articles that briefly talk about long term effects such as confusion and cardiovascular issues that can last for months. With the virus still being so new scientists don’t have a clear understanding of how these effects will impact people over time, so I think that investigating that would be a great step forward.

Jcorrey (talk) 23:22, 14 October 2020 (PDT)

Kam Taghizadeh

1. In addition to the scientific conclusion for your project, reflect on what you learned as a person by performing this research. Describe what you learned with your head (scientific knowledge), hands (technical skills), and heart (personal or teamwork qualities needed to succeed as a scientist).
   • I learned a lot about the various mutations that could alter the binding affinity of RBD to human ACE2. There were a lot of technical difficulties that got in the way of my learning however, and this was discussed with my partner. Teamwork is critical for a project like this.
2. What is still not clear to you after having concluded this project?
   • I'm still not entirely sure what the reason for increased binding affinity is when there is a mutation at position 501. Not enough research has been done, as I had gone through absolutely every article regarding position 501 in RBD on google scholar.
3. If you had more time (anywhere from a few more weeks to a couple of years, like, for example, a Master's thesis project), what future directions would you like to take for this project? You will have the opportunity to conduct a second, more in-depth research project in the latter part of the semester.
   • I would want to know exactly what leads to a higher binding affinity by testing substitutions at position 501.

Kam Taghizadeh (talk) 00:53, 15 October 2020 (PDT)

Taylor Makela

1. In addition to the scientific conclusion for your project, reflect on what you learned as a person by performing this research. Describe what you learned with your head (scientific knowledge), hands (technical skills), and heart (personal or teamwork qualities needed to succeed as a scientist).
   • Overall, I learned a lot by performing this research. For one, I learned a lot about sequencing, hotspots, receptors, and about how binding of proteins works for SARS-CoV and 2019-nCoV. As far as technical skills go, I really enjoyed working with the different tools and databases and I feel much more confident in working with them to hopefully conduct more research in the future!
2. What is still not clear to you after having concluded this project?
   • I am still not clear on exactly how conducting this type of research could lead to a vaccine (i.e. what additional steps would need to be taken?).
3. If you had more time (anywhere from a few more weeks to a couple of years, like, for example, a Master's thesis project), what future directions would you like to take for this project? You will have the opportunity to conduct a second, more in-depth research project in the latter part of the semester.
   • I would like to look more in depth into the 2019-nCoV specifically (rather than SARS-CoV) so that I could better understand our current coronavirus. We initially tried to this for our first project, but because 2019-nCoV is so new, there is not as much data for the species and therefore it would take more time to try to research and find the necessary data to then perform a similar analysis to our first project.

Taylor Makela (talk)

Nida Patel Response

1. In addition to the scientific conclusion for your project, reflect on what you learned as a person by performing this research. Describe what you learned with your head (scientific knowledge), hands (technical skills), and heart (personal or teamwork qualities needed to succeed as a scientist).
   • I learnt plenty about the binding of RBD and the ACE2 receptor, this information bettered my understanding of the difficulties of the SARS_CoV-2 pandemic as well as the mechanism of action of the virus. I also became familiar with the use of databases and scientific tools, now I am comfortable with creating phylogenetic trees and sequencing genomes of multiple species.
2. What is still not clear to you after having concluded this project?
   • I am still unclear on how antibodies play a part in successful viral curation, are antibodies included inside of vaccines?
3. If you had more time (anywhere from a few more weeks to a couple of years, like, for example, a Master's thesis project), what future directions would you like to take for this project? You will have the opportunity to conduct a second, more in-depth research project in the latter part of the semester.
   • I would like to look more in depth into the antibody competition between the ACE2 receptor and antibodies. I would like to familiarize myself with the curation process of antibodies and the process in isolating successful antibodies.