The Microbiome and Drug Delivery: Cross-species Communication in Health and Disease

Readings

WEEK #	TOPICS	READINGS
1	Introduction to the human microbiome See the Lecture Summary	No Readings
Small-molecule Signals, Microfluidics and Synthetic Biology
2	Microbes use small molecules to communicate See the Lecture Summary	Seed, Patrick C., Luciano Passador, et al. “Activation of the Pseudomonas Aeruginosa LasI Gene by LasR and the Pseudomonas Autoinducer PAI: An Autoinduction Regulatory Hierarchy.” Journal of Bacteriology 177, no. 3 (1995): 654–9. Passador, Luciano, Kenneth D. Tucker, et al. “Functional Analysis of the Pseudomonas Aeruginosa Autoinducer PAI.” Journal of Bacteriology 178, no. 20 (1996): 5995–6000.
3	Microfluidics technology to study the human microbiome See the Lecture Summary	Hong, Seok Hoon, Manjunath Hegde, et al. “Synthetic Quorum-sensing Circuit to Control Consortial Biofilm Formation and Dispersal in a Microfluidic Device.” Nature Communications 3, no. 613 (2012). Luo, Xiaolong, Chen-Yu Tsao, et al. “Distal Modulation of Bacterial Cell-cell Signalling in a Synthetic Ecosystem Using Partitioned Microfluidics.” Lab on a Chip 15, no. 8 (2015): 1842–51.
4	Field trip to Ginkgo Bioworks, the organism company See the Lecture Summary	Endy, Drew. “Foundations for Engineering Biology.” Nature 438 (2005): 449–53. Kwok, Roberta. “Five Hard Truths for Synthetic Biology.” Nature 463 (2010): 288–90.
5	Microbes engineered to detect and potentially kill pathogens See the Lecture Summary	Danino, Tal, Arthur Prindle, et al. “Programmable Probiotics for Detection of Cancer in Urine.” Science Translational Medicine 7, no. 289 (2015): 289ra84. Saeidi, Nazanin, Choon Kit Wong, et al. “Engineering Microbes to Sense and Eradicate Pseudomonas Aeruginosa, a Human Pathogen.” Molecular Systems Biology 7, no. 521 (2011).
Peptide Signals for Defense, Therapeutics and Competence
6	Microbes use peptides as a defense and as signals See the Lecture Summary	Brötz, Heike, Michaele Josten, et al. “Role of Lipid-bound Peptidoglycan Precursors in the Formation of Pores by Nisin, Epidermin and Other Lantibiotics.” Molecular Microbiology 30, no. 2 (1998): 317–27. de Ruyter, Pascalle G., Oscar P. Kuipers, et al. “Controlled Gene Expression Systems for Lactococcus Lactis with the Food-grade Inducer Nisin.” Applied and Environmental Microbiology 62, no. 10 (1996): 3662–7.
7	Drug delivery using microbes engineered to secrete peptides See the Lecture Summary	Rao, Srinivas, Stella Hu, et al. “Toward a Live Microbial Microbicide for HIV: Commensal Bacteria Secreting an HIV Fusion Inhibitor Peptide.” Proceedings of the National Academy of Sciences of the United States of America 102, no. 34 (2005): 11993–8. Blanquet, Stéphanie, Richard Antonelli, et al. “Living Recombinant Saccharomyces Cerevisiae Secreting Proteins or Peptides as a New Drug Delivery System in the Gut.” Journal of Biotechnology 110, no. 1 (2004): 37–49.
8	Competence-stimulating peptides as cross-species signals See the Lecture Summary	Håvarstein, Leiv Sigve, Gowri Coomaraswamy, et al. “An Unmodified Heptadecapeptide Pheromone Induces Competence for Genetic Transformation in Streptococcus Pneumoniae.” Proceedings of the National Academy of Sciences of the United States of America 92, no. 24 (1995): 11140–4. Jarosz, Lucja M., Dong Mei Deng, et al. “Streptococcus Mutans Competence-stimulating Peptide Inhibits Candida Albicans Hypha Formation.” Eukaryotic Cell 8, no. 11 (2009): 1658–64.
The Future of the Microbiome for Human Health
9	Using seminars and talks for sharing scientific discoveries See the Lecture Summary	View video and prepare for discussion: Chris Voigt. “Genetic Circuits: Programming Living Bacteria.” July, 2015. iBiology.
10	Advance culturing techniques to study microbiomes See the Lecture Summary	Samuel, Buck S. & Jeffery Gordon. “A Humanized Gnotobiotic Mouse Model of Host-archaeal-bacterial Mutualism.” Proceedings of the National Academy of Sciences of the United States of America 103, no. 26 (2016): 10011–6. Kim, Hyun Jung, Hu Li, et al. “Contributions of Microbiome and Mechanical Deformation to Intestinal Bacterial Overgrowth and Inflammation in a Human Gut-on-a-chip.” Proceedings of the National Academy of Sciences of the United States of America 113, no. 1 (2016): E7–E15 .
11	Host-generated peptides shape their microbiomes See the Lecture Summary	Ghosh, Dipankar, Edith Porter, et al. “Paneth Cell Trypsin is the Processing Enzyme for Human Defensin-5.” Nature Immunology 3, no. 6 (2002): 583–90. Cullen, T. W., W. B. Schofield, et al. “Antimicrobial Peptide Resistance Mediates Resilience of Prominent Gut Commensals During Inflammation.” Science 347, no. 6218 (2015): 170–5.
12	Microbes as neuromodulators See the Lecture Summary	Heijtz, Rochellys Diaz, Shugui Wang, et al. “Normal Gut Microbiota Modulates Brain Development and Behavior.” Proceedings of the National Academy of Sciences of the United States of America 108, no. 7 (2011): 3047–52. Thaiss, Christoph A., David Zeevi, et al. “Transkingdom Control of Microbiota Diurnal Oscillations Promotes Metabolic Homeostasis.” Cell 159, no. 3 (2014): 514–29.
13	Microbes as cancer therapeutics See the Lecture Summary	Zhao, Ming, Jack Geller, et al. “Monotherapy with a Tumor-targeting Mutant of Salmonella Typhimurium Cures Orthotopic Metastatic Mouse Models of Human Prostate Cancer.” Proceedings of the National Academy of Sciences of the United States of America 104, no. 24 (2007): 10170–4. Anderson, J. Christopher, Elizabeth J. Clarke, et al. “Environmentally Controlled Invasion of Cancer Cells by Engineered Bacteria.” Journal of Molecular Biology 355, no. 4 (2006): 619–27.
14	Oral presentations, conclusion and closing remarks See the Lecture Summary	No Readings