Biology of restriction-modification systems at the single-cell and population level

M. Pleska, Biology of Restriction-Modification Systems at the Single-Cell and Population Level, IST Austria, 2017.

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Thesis | Published | English
Department
Series Title
IST Austria Thesis
Abstract
Restriction-modification (RM) represents the simplest and possibly the most widespread mechanism of self/non-self discrimination in nature. In order to provide bacteria with immunity against bacteriophages and other parasitic genetic elements, RM systems rely on a balance between two enzymes: the restriction enzyme, which cleaves non-self DNA at specific restriction sites, and the modification enzyme, which tags the host’s DNA as self and thus protects it from cleavage. In this thesis, I use population and single-cell level experiments in combination with mathematical modeling to study different aspects of the interplay between RM systems, bacteria and bacteriophages. First, I analyze how mutations in phage restriction sites affect the probability of phage escape – an inherently stochastic process, during which phages accidently get modified instead of restricted. Next, I use single-cell experiments to show that RM systems can, with a low probability, attack the genome of their bacterial host and that this primitive form of autoimmunity leads to a tradeoff between the evolutionary cost and benefit of RM systems. Finally, I investigate the nature of interactions between bacteria, RM systems and temperate bacteriophages to find that, as a consequence of phage escape and its impact on population dynamics, RM systems can promote acquisition of symbiotic bacteriophages, rather than limit it. The results presented here uncover new fundamental biological properties of RM systems and highlight their importance in the ecology and evolution of bacteria, bacteriophages and their interactions.
Publishing Year
Date Published
2017-10-01
Acknowledgement
During my PhD studies, I received help from many people, all of which unfortunately cannot be listed here. I thank them deeply and hope that I never made them regret their kindness. I would like to express my deepest gratitude to Călin Guet, who went far beyond his responsibilities as an advisor and was to me also a great mentor and a friend. Călin never questioned my potential or lacked compassion and I cannot thank him enough for cultivating in me an independent scientist. I was amazed by his ability to recognize the most fascinating scientific problems in objects of study that others would find mundane. I hope I adopted at least a fraction of this ability. I will be forever grateful to Bruce Levin for all his support and especially for giving me the best possible example of how one can practice excellent science with humor and style. Working with Bruce was a true privilege. I thank Jonathan Bollback and Gašper Tkačik for serving in my PhD committee and the Austrian Academy of Science for funding my PhD research via the DOC fellowship. I thank all our lab members: Tobias Bergmiller for his guidance, especially in the first years of my research, and for being a good friend throughout; Remy Chait for staying in the lab at unreasonable hours and for the good laughs at bad jokes we shared; Anna Staron for supportively listening to my whines whenever I had to run a gel; Magdalena Steinrück for her pioneering work in the lab; Kathrin Tomasek for keeping the entropic forces in check and for her FACS virtuosity; Isabella Tomanek for always being nice to me, no matter how much bench space I took from her. I thank all my collaborators: Reiko Okura and Yuichi Wakamoto for performing and analyzing the microfluidic experiments; Long Qian and Edo Kussell for their bioinformatics analysis; Dominik Refardt for the λ kan phage; Moritz for his help with the mathematical modeling. I thank Fabienne Jesse for her tireless editorial work on all our manuscripts. Finally, I would like to thank my family and especially my wife Edita, who sacrificed a lot so that I can pursue my goals and dreams.
Page
126
IST-REx-ID

Cite this

Pleska M. Biology of Restriction-Modification Systems at the Single-Cell and Population Level. IST Austria; 2017. doi:10.15479/AT:ISTA:th_916
Pleska, M. (2017). Biology of restriction-modification systems at the single-cell and population level. IST Austria. https://doi.org/10.15479/AT:ISTA:th_916
Pleska, Maros. Biology of Restriction-Modification Systems at the Single-Cell and Population Level. IST Austria, 2017. https://doi.org/10.15479/AT:ISTA:th_916.
M. Pleska, Biology of restriction-modification systems at the single-cell and population level. IST Austria, 2017.
Pleska M. 2017. Biology of restriction-modification systems at the single-cell and population level, IST Austria, 126p.
Pleska, Maros. Biology of Restriction-Modification Systems at the Single-Cell and Population Level. IST Austria, 2017, doi:10.15479/AT:ISTA:th_916.
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