- You are interested in trying to determine if the bacterial microbiome is relevant in rheumatoid arthritis (you may want to read briefly about what rheumatoid arthritis is and how it is diagnosed). Outline at least two different experimental approaches for identifying relevant bacteria and then outline how you would test Koch’s postulates to demonstrate pathogenic relevance [See: Greiling et al. (2018)]. Please include details on how your approaches will be informative to the hypothesis.
- The efficacy of L-dopa treatment is hugely variable between individuals, depending on microbiome composition. For L-dopa to be efficacious, it must cross the blood brain barrier prior to decarboxylation to the active compound dopamine. In 2019, Rekdal (https://science.sciencemag.org/content/364/6445/eaau6323) and coworkers identified how the microbiome influences L-dopa treatment for Parkinson’s disease. Briefly, design a metabolomics centered experimental outline to identify the microbes responsible, validate their role in L-dopa metabolism, and development of an inhibitor of the microbial enzyme.
- Explain how influenza virus infection is enhanced in microbiota-depleted mice that are orally-administered broad-spectrum antibiotics but influenza virus transmission is inhibited when donor ferrets are nasally-administered mupirocin antibiotic ointment. Using knowledge gained from past publications (https://msystems.asm.org/content/5/5/e00762-20) regarding influenza virus-microbiota interactions, design one or more experiments to help clarify and rectify the divergence in these data. (It may help to design experiments first.)
- You have been tasked with determining whether there is or is not a microbial community associated with the lower lobes of the human lung. What criteria would you use to decide this question? How would a DNA sequencing approach (either 16S rRNA or shotgun metagenomics) help or be limited in answering this question? A comprehensive answer should include the following in order to receive full points:
- What criteria would you use to decide this question? How would you define a “community” vs “accidental tourists”? Explain your logic, not just the methodology.
- How would a DNA sequencing approach (either 16S rRNA or shotgun metagenomics) help or be limited in answering this question? When answering be sure to demonstrate a clear rationale for methods. And identify key benefits and limitations.
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