26.9.2020 Research shows how CRISPR-Cas protects a fish pathogen against phages (Hoikkala)

CRISPR-Cas is a molecular toolbox that has enabled gene editing with unprecedented efficiency. In nature, CRISPR-Cas protects bacteria by recognizing and destroying previously encountered bacterial viruses, phages. As the DNA-encoded phage memories are inherited by daughter cells, CRISPR-Cas provides a unique window into phage-bacterium coevolution. The details of this coevolution, however, are still largely unknown, especially in less-studied species. In his PhD dissertation that will be examined in the Ģֱ, Ville Hoikkala studied how CRISPR-Cas functions in the fish pathogen Flavobacterium columnare.
Published
26.9.2020

F. columnare is the causative agent of the columnaris fish disease. The bacterium’s genome contains two CRISPR-Cas systems, one of which targets DNA and while the other targets RNA. To understand how these mysterious memory systems work, Ville Hoikkala studied them in both natural communities and in the laboratory.

Natural coevolution between phages and bacteria were tracked from a seven-year sample collection. The CRISPR-arrays were found to acquire new memories over time, while phages were found to alter their genome, possibly in response to these memories. Laboratory experiments revealed more details, showing how these CRISPR-Cas arrays cooperate and how a fish chemical signal may intensify their activity.

Understanding CRISPR-Cas systems may provide new molecular tools

Less-known CRISPR-Cas systems may provide new innovations for biotechnology. In addition to gene editing, RNA-targeting CRISPR-Cas systems were recently harnessed for diagnostic use with COVID-19.

“Molecular tools found in bacteria and viruses are essential in modern laboratory work and medicine, with new innovations being constantly discovered from less-known species”, says Ville Hoikkala

The work also benefits phage therapy – a treatment where bacterial disease is treated with phages.

“To prevent the rise of phage resistance in bacteria, we must obtain a thorough understanding of how bacteria immunize themselves against phages” Ville Hoikkala emphasizes.

The study also show that F. columnare uses a multitude of defenses other than CRISPR-Cas against phages infections.

The study has been published in the Ģֱ dissertation series JYU Dissertations 276, Jyväskylä 2020, ISSN 2489-9003, ISBN 978-951-39-8264-5 (PDF). The publication can be found in the JYX publication archive

Ville Hoikkala graduated from Jyväskylän Lyseon Lukio -high school in 2008 and obtained his master’s from the Ģֱ in 2015 with a major in cell and molecular biology and minors in evolutionary genetics and information technology. He began his PhD studies in 2016 in Lotta-Riina Sundberg’s group after working with CRISPR-Cas as a project researcher in 2015.

For further information:
Ville Hoikkala, ville.hoikkala@jyu.fi

M.Sc. Ville Hoikkala defends his doctoral dissertation in Cell and Molecular Biology "Memoirs of a fish pathogen: how CRISPR-Cas captures phage encounters in Flavobacterium columnare" in September 26th at the Ģֱ. Opponent Professor is Edze Westra (University of Exeter, UK) and Custos is Associate Professor Lotta-Riina Sundberg (Ģֱ). The doctoral dissertation is held in English.

The audience can follow the dissertation online.  Link to the Zoom Webinar (Zoom application or Google Chrome web browser recommended):