May 5

Climate Choices Deliberation Forum Reflection

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Climate Choices Deliberation Forum Reflection

Did any of the Options appeal to you more than the others?

Yes, option 1 appealed to me more than the others because, to me, it seemed like the only option that was guaranteed to make anything better. Scientifically, we know that human carbon emissions are contributing massively to the problem of global warming and if we reduce these emissions radically then we can tackle the problem. I feel like option 2 is kind of a cop-out that will not guarantee any positive outcomes, and option 3 would be a good idea if there could be actual guarantees. I think that even though radically reducing carbon emissions would mean some individual discomfort, I think it would be better in the long run.

Did you hear or think of any new way of addressing the issues associated with the warming of the climate?

I didn’t think about adapting our communities to deal with the consequences of climate change until the discussion. I don’t think it is a good idea, but I’d never considered it before.

What are your thoughts on the use of Public Deliberation in the classroom or the community? Is this something you would like to facilitate?

I really like the use of Public Deliberation in the classroom because I feel like it is an easy way to learn a lot of perspectives on the same issue very quickly. I think it works best with controversial issues after everyone has a basic understanding of the issue because it creates a free flow of ideas. I’ve never experienced Public Deliberation on a community level, but I imagine it would be good for increasing understanding between different groups, so I believe it to be a useful tool. I think if I had time it is something I would love to facilitate.

 

April 26

Final Abstract Writing and Research Wrap Up 4/24/19

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Final Abstract Writing and Research Wrap Up 4/24/19

Rationale

The rationale behind today in lab was to create a final abstract in preparation for our final presentation. In addition, when we were done with our abstract, we continued working on sequencing and protein folding in order to collect the necessary data.

Tools/Procedure

  1. Final abstract was submitted
  2. MEME Motif was used to find repeating motifs in the TMPs of selected proteins from each usable cluster
  3. The phylogenetic tree generated by ClustalOmega was used to examine if motifs appeared to be related

Results

The results above were generated using the MEME software to find motifs. The logo above represents a motif that was found in almost all 43 selected TMPs suggesting an area of conservation. In addition, when searching for other common motifs several appeared with much less frequency but much more similarity, which will require further research. This motif shows that there is less similarity in the actual amino acid sequences, but the color coding suggests that structure is more likely to be conserved as many of the amino acids at a location are color-coded the same, suggesting that the amino acids will behave very similarly. In addition, while analysis of the phylogenetic tree is incomplete, it appears that there are definite examples of motifs being related to each other.

***I made a mistake when I previously reported that the motifs were found in all 43 sequences, while some are, the biggest one I found was not and I now need to examine the implications of this***

Conclusion

The motifs I’ve found suggest that there areas of conserved amino acids, but maybe not one unifying motif that I wanted to find.

Future Plans

In the future, we will continue to look for similarities and difference in the amino acid while continuing our folding of proteins to try to figure out what to make of the conserved regions we’ve found in TMPs. We will also complete our final research presentation.

April 24

Forgotten Cure Assignment Part 3 4/23/19

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Forgotten Cure Assignment Part 3 4/23/19

2. One of the biggest problems in phage therapy has been in the approval process. Describe the trouble surrounding FDA approval and recommend some suggestions to improve the process of phage therapy approval.

One of the biggest issues that Sulakvelidze had was the FDA’s unrealistic expectations because phage do not work the same way antibiotics do, they cannot be tested or treated the same way during the approval process. Phage mutate and change so often that constantly sequencing every new phage in a cocktail is prohibitively expensive. Sulakvelidze and his company did not have the funding to do all of the necessary testings for FDA approval, so they had to put their VRE project on hold. A similar issue was faced by GangaGen so they, like Sulakvelidze, chose to focus on animal applications first. Many of these issues stem from an FDA approval system that does not understand bacteriophage and underfunded research.

I think that the easiest way to improve the process of phage therapy approval is to improve the basic research of phage first. When the author describes the conference held by GangaGen, Ry Young calls for a renaissance in phage research, and while this idea was initially not as well received at the conference, I think it would improve the process of phage therapy approval. I think if more were understood about phage in the first place it might make the FDA approval process easier because there would be less unanswered questions, and much of the research that small start-up companies do not have the funding to do could be done, at least conceptually, as part of the process of learning more about bacteriophage. In addition, I think that Sulakvelidze and GangaGen were smart to realize that it is easier to work with animals first. By focusing on making food products safe first, these companies were exposed to the approval process at less stringent standards and helped normalize phage. While this won’t directly improve the process of phage therapy approval in humans, I think that using phage in other industries first would help make phage product testing more uniform and easier to cross apply to people over time. I think that with a larger body of phage research, and phage usage in other industries the approval process would be improved and some of the concerns the FDA outlined when working with Sulakvelidze would be mitigated.

April 12

Progress Report and Continued Research 4/10/19

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Progress Report and Continued Research 4/10/19

Rationale

The rationale behind today in lab was to search the literature to have us submit a progress report so that we and our coaches could see where we are at and what still needs to be done. In addition, when we were done with our progress report, we continued working on sequencing and protein folding in order to collect the necessary data.

Tools/Procedure

  1. Progress report was submitted
  2. Clustal Omega was used to compare TMPs between individual Arthrobacter clusters and between different tail morphologies
    1. Sipho and myo family groups were compared
  3. MEME Motif was used to find repeating motifs in the TMPs of sipho and myo phage

Results

The results above were generated using the MEME software to find motifs, areas of similar sequences across several different sequences belonging to both sipho and myo phage. As can be seen in the motif location image, there are two motifs (shown in blue and in green) that are present in every TMP tested, creating intriguing information to look into.

Conclusion

While there is not enough data to make extensive conclusions yet, our data so far suggests that TMPs are highly conserved (based on amino acid sequences) in each cluster, and less conserved in the tail families. The amino acid sequences do however suggest certain structural elements being conserved among tail families even if the amino acid sequence is not strictly conserved. Also, protein folding between myo and sipho phage showed significant differences in the protein structure, which we will need to examine further. Finally the results that show there are certain motifs found in every TMP seem to suggest areas of conservation.

Future Plans

In the future, we will continue to look for similarities and difference in the amino acid while continuing our folding of proteins to try to figure out if there are key conserved regions in TMPs.

April 12

Literature Search Report 4/8/19

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Literature Search Report 4/8/19

Rationale

The rationale behind today in lab was to search the literature to help us better understand what we are researching and to see if we can find valuable insights. In addition, when we were done with our literature search, we continued working on sequencing and protein folding in order to collect the necessary data.

Tools/Procedure

  1. Five sources of primary literature were cited and submitted
  2. Clustal Omega was used to compare TMPs between individual Arthrobacter clusters and between different tail morphologies
    1. AK, AL, AM, and all F clusters were compared

Results

The clustal omega results shown above help illustrate the results that were found during this lab period. While there is an incredible similarity between TMPs of the same cluster, even TMPs from the same tail morphology, but different clusters show fairly significant differences in the amino acid sequences. However, there does seem to be more similarity between the types of amino acids (as seen by the color coding) suggesting that even if DNA or amino acid sequences are not highly conserved, the structure is more likely to be conserved.

Conclusion

While there is not enough data to make extensive conclusions yet, our data so far suggests that TMPs are highly conserved (based on amino acid sequences) in each cluster, and less conserved in the tail families. The amino acid sequences do however suggest certain structural elements being conserved even if the amino acid sequence is not strictly conserved.

Future Plans

In the future, we will continue to look for similarities and difference in the amino acid while continuing our folding of proteins to try to figure out if there are key conserved regions in TMPs.

April 5

Individual Project Final Outline 4/3/19

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Individual Project Final Outline 4/3/19

Rationale

The rationale behind today in lab was to create a final outline of our final project so that we have a good basis of information moving forward. This outline also served as a plan that we can use to accomplish our goals.

Tools/Procedure

  1. A final outline was created and submitted
  2. All 23 clusters of Arthrobacter phage were classified
  3. A random number generator was used to pick 3 phages from each cluster for further examination

Results

Our final outline can be seen above, it is on this that we will base the rest of our research. We also began the process of randomly picking the phage whose proteins we will analyze, and I will further detail that in future reports.

Conclusion

There is not much that can be said as a conclusion as this was a planning session, but we did discover that of the 4 podovirade phages that are on phages DB not one calls a tape measure proteins. This may be something interesting to look into in the future,

Future Plans

In the future, we will continue our research based on the plan we laid out above.

March 28

Individual Projects, Topic Generation 3/26/19

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Individual Projects, Topic Generation 3/26/19

Rationale

The rationale behind these procedures is to ensure that Rachel and I can come up with research topics for our individual project that can actually be answered in the time available while also providing a valuable amount of information.

Tools/Procedure

  1. Previously created groups brainstormed 4 potential research questions for the individual research projects
  2. Groups consulted with their assigned coaches in order to further develop their research questions and understand what elements must be present in their research questions
  3. Changes were made as necessary

Results

The image above shows the several questions Rachel and I generated as potential research topics and our responses to/ notes on coaching advice. These questions represent a rough draft of sorts that we will explore while trying to figure out what exactly we will be researching and how we will narrow down our topic further.

Conclusion

There is not much that can be said as a conclusion as this was a brainstorming day. I can say that Rachel and I will likely work with our potential question number three because Lathan and Dr. Adair seemed to like it most and think it was the most testable question that would still yield good information.

Future Plans

In the future, we will continue working to finalize a research topic and begin our individual research project once our topic has been fully determined.

March 18

Forgotten Cure Part Two

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Forgotten Cure Part Two

1. How did having a state health system influence the treatment of infectious disease in 1940s-50s Russia?

The state health system was underfunded, so while it tried to provide health care for all, it was often short on resources (like money and antibiotics). This was an embarrassment to the Soviet Union, so it relied on propaganda to discourage the use of antibiotics to treat infectious disease. This propaganda encouraged citizens to rely on alternative medicines like herbs, and because phage therapy was also considered alternative medicine, it became more popular as a treatment for infectious disease during that time.

2. The Hirszfeld Institute is also intertwined with Russian history. A tragic quote is given on page 66 by Hirszfeld about the death of his daughter. Even so, the outcome of these 2 centers has been very different. Discuss why you think this is so. Contrast the Phage Therapy Center in Wroclaw with the Eliava Institute in Tbilisis.

The Phage Therapy Center might have succeeded where the Eliava Institute did not because of the differences in their founding, focus, and support. The Phage Therapy Center was supported by the Polish government after the end of World War 2 and became better established afterward. The Eliava Institute, by contrast, lost funding towards the end of world war 2 and focused more on phage. The two different political climates surrounding these institutions can account for the differences in what happened to them.

3. Research in the USA often differs from other countries because of regulations by the FDA and private investments. Describe the experimental design that Merril used to determine how to select for phages that were not removed by the liver and spleen. Review the Merril, Carlton, and Adhya PNAS paper, focusing on interpreting their figures.

For his experimental design, Merril injected lambda phage into mice and tested for the presence of phage in the blood after 7 hours. He then selected the remaining phage from the parent testing and used serial-passage techniques to select the phages Argo 1 and Argo 2 that survived longer than the original parent lambda phage (around 18 hours). This was done by selecting the remaining phage and reinjecting the mice 8 times. As can be seen in the figures below, Argo 1 and Argo 2 persisted in the blood longer that the wild type at high concentrations.

These passaged phages were then used in another experiment to demonstrate their effectiveness against E. coli. Four groups of mice were infected with a lethal dose of the bacteria and three were treated with phage (Argo 1, Argo 2, or wild-type phage) and one was left as a control. The ones treated with phage were more likely to survive, and Argo 1 and Argo 2 phage treatments seemed to lessen the disease severity.

4. The most convincing argument for using phage is tied to the increasing problem of antibiotic resistance. Even so, many still consider phage therapy an alternative therapy. Chapter 8 describes several start-up companies: Phage Therapy, Phage Biotics, GangaGen, Exponential Biotherapies. Research these companies and discuss the potential for phage therapy in modern Western medicine. What experiments need to be done?

Personally, I think that for phage therapy to lose the label of alternative medicine and be fully embraced by Western Medicine science alone will not be sufficient. I think that Phage Therapy in the west has been hurt by associations with eastern medicine and the soviet union. I think that double-blind experiments do need to be done and continued, but I also think prominent western scientists will need to lend their support to phage therapy. In addition to a bit of a PR campaign, more experimental data showing the use of phage and antibiotics together to combat antibiotic resistance would be beneficial. Finally, what I found to be most intriguing was mention in the book, the author said that many bacteria that developed a resistance to phage seemed to mutate into a harmless, avirulent form of the bacteria. If there could be experiments done that showed that bacteria tended to become avirulent when becoming resistant to phage not only would that revolutionize how we treat disease, but it would also help phage therapy.

March 8

Large Group Poster Creation 3/4/19

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Large Group Poster Creation 3/4/19

Rationale

The rationale behind these procedures is to ensure that poster creations for Scholar’s day follow the correct format and that basic poster requirements are understood. The procedures were also done to give practice for poster making and create a draft for Scholar’s Day.

Tools/Procedure

  1. Previously created groups were combined and worked together to create poster drafts based on previous instruction
    • Poster layout and design was created by blending the ideas of each group
    • Class data from last semester were examined and graphics were created based on these data
    • Methods were described in graphic format
    • Data from both semesters were compiled and results were reported
  2. The poster draft was submitted

Results

The above poster layout was designed by Rachel and I in conjunction with Cooper, Joseph, and Henry it is just a draft, but it demonstrates an understanding of scientific poster making and we did our best to include information that we would want to be included.

Conclusion

Lab period today was not used for any scientific research, but I can say that I demonstrated my understanding of poster making.

Future Plans

In the future, we will be working as a class to create a poster for Scholar’s day.

March 1

Small Group Poster Creation 2/27/18

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Small Group Poster Creation 2/27/18

Rationale

The rationale behind these procedures is to ensure that poster creations for Scholar’s day follow the correct format and that basic poster requirements are understood. The procedures were also done to give practice for poster making and create a draft for Scholar’s Day.

Tools/Procedure

  1. Previously created groups worked together to create poster drafts based on previous instruction
    • Poster layout and design was created based on previously created poster sketch
    • Class data from last semester were examined and graphics were created based on these data
    • Methods were described in graphic format
    • Data from both semesters were compiled and results were reported
  2. The poster draft was submitted

Results

The above poster layout was designed by Rachel and I, it is just a draft, but it demonstrates an understanding of scientific poster making.

Conclusion

Lab period today was not used for any scientific research, but I can say that I demonstrated my understanding of poster making.

Future Plans

In the future, I will continue working with Rachel and then with larger groups to create a poster for Scholar’s day.