Engineered endosymbiosis: what would be some amazing collaborations?
Image credit: National Institutes of Health (NIH)
- What are some microbial species with amazing superpowers that would be beneficial to our cells?
- How could we ensure symbiosis? The newly introduced symbiont should not turn on the host cell somewhere down the line.
- What are the obstacles to work on before something like this can become a reality?
Mimic endosymbiosis: models and example
- How do we make it?
- What are the side-effects, if any?
- What are the benefits, if any?
- Do the benefits outbalance the side-effects?
- How can we maintain a stable endosymbiotic situation? SNARE-like proteins may be an answer. May we look at our microbiota to understand which would be the key factors in terms of expressed genes that are amenable? To this extent models using Drosophila melanogaster are already available to study the host immune system control over gut microbiome .
- What kind of dependency should we install in the selected microorganism? Those will be GMO and we have to avoid a horizontal genetic transfer. So we should develop a control system not readily available in nature, to avoid an undesired "escape".
Engineering yeast endosymbionts as a step toward the evolution of mitochondria Angad P. Mehta, Lubica Supekova, Jian-Hua Chen, Kersi Pestonjamasp, PaulWebster, Yeonjin Ko, Scott C. Henderson, Gerry McDermott, FrantisekSupek, Peter G. Schultz
Ludington WB, Ja WW (2020) Drosophila as a model for the gut microbiome. PLoS Pathog 16(4): e1008398. https://doi.org/10.1371/journal.ppat.1008398
Nigro G, Hanson M, Fevre C, Lecuit M, Sansonetti PJ. Intestinal Organoids as a Novel Tool to Study Microbes-Epithelium Interactions. Methods Mol Biol. 2019;1576:183-194. doi: 10.1007/7651_2016_12. PMID: 27628134.
Chowdhury, S., Castro, S., Coker, C. et al. Programmable bacteria induce durable tumor regression and systemic antitumor immunity. Nat Med 25, 1057–1063 (2019). https://doi.org/10.1038/s41591-019-0498-z
Endosymbiosis engineering for containing anti-oxidant producing bacterial species
 Schieber M., Chandel N.S. ROS function in redox signaling and oxidative stress. Curr. Biol. 2014;24:R453–R462. doi: 10.1016/j.cub.2014.03.034
Luo D., Fang B. Structural identification of ginseng polysaccharides and testing of their antioxidant activities. Carbohydr. Polym. 2008;72:376–381. doi: 10.1016/j.carbpol.2007.09.006.
Lin, X., Xia, Y., Wang, G., Yang, Y., Xiong, Z., Lv, F., Zhou, W., & Ai, L. (2018). Lactic Acid Bacteria With Antioxidant Activities Alleviating Oxidized Oil Induced Hepatic Injury in Mice. Frontiers in Microbiology, 9, 1–17. https://doi.org/10.3389/fmicb.2018.02684
What causes parts of symbiont's DNA to move to the host cell's nucleus?
- What mechanism "decides" to cut out parts of a bacterial cell's DNA?
- Does the decision come from the bacteria or the host cell?
- What mechanism "decides" whether to incorporate the genes into the host cell's nucleus or throw them out?
Make the symbiont's DNA incomplete without the host cell's DNA
Nitrogen fixing bacteria within our skin cells
Deinococcus radiodurans as safe-keeper of the host cell's DNA
- Could it somehow be turned into an organelle that keeps our nuclear DNA safe and makes sure that the master copy is not damaged?
- Could it be repurposed to do the job of Mitochondria? If so, its function would not be prone to damage with age.
Minton KW. DNA repair in the extremely radioresistant bacterium Deinococcus radiodurans. Mol Microbiol. 1994 Jul;13(1):9-15. doi: 10.1111/j.1365-2958.1994.tb00397.x. PMID: 7984097.