Copenhagen Bioscience Snapshot: Evolutionary Genomics with Dr. Eugene Koonin and Prof. Dr. John van der Oost
In this snapshot, our speakers will share insights about their decades-long research in the field of microbiology and virology. Both speakers have played a pivotal role in uncovering the function of the now widely used CRISPR-Cas system, originally a bacterial weapon against bacteriophages. First, Dr. Koonin will guide us through the world of viruses, and how advances in genomics allow for an increased understanding of their evolutionary history. Later, Prof. Dr. Van der Oost will elaborate on the discovery of the CRISPR-Cas system and how it lead to the development of the powerful genetic engineering tool for which it is now known.
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Background
The Copenhagen Bioscience Snapshots are a series of seminar events organized by PhD students of the Copenhagen Bioscience PhD programme since 2019. The seminars host speakers from different scientific backgrounds aiming to connect a broad audience of scientists. Stay tuned for more seminars in 2021.
Description
Dr. Eugene Koonin: The world of viruses, its global organization and evolution – National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA
Viruses and virus-like mobile genetic elements are ubiquitous parasites (and sometime symbionts) of all cellular life forms and the most abundant biological entities on earth. The recent, unprecedented advances of comparative genomics and metagenomics have led to the discovery of diverse novel groups of viruses and provide for a vastly improved understanding of the evolutionary relationships within the virosphere. Arguably, we are approaching the point when the global architecture of the virus world can be outlined in its entirety, and the key evolutionary events in each of its domains can be reconstructed.
I will present such an outline of the global organization of the virus world and the corresponding megataxonomy structure that has been recently approved by the International Committee for Taxonomy of Viruses. In particular, I will present the comprehensive evolutionary tree of RNA viruses and discuss the positions of the viruses that cause major human diseases in the different branches of this tree. It is of note that coronaviruses, including SARS-CoV-2, possess the largest and most complex genomes among the RNA viruses known to date, arguably, reflecting the complexity of the virus-host interactions. Although the global structure of the virus world is becoming apparent, major groups of viruses within the established realms, with unique features of genome organization and expression, are being discovered at a high pace. Examples of such new viruses will be presented including the most abundant bacteriophages in the human gut. I will conclude by outlining the major trends in SARS-CoV-2 evolution revealed by phylogenetic analysis of hundreds of thousands of virus genome.
Prof. Dr. John van der Oost: CRISPR-Cas – from biology to applications –Laboratory of Microbiology, Wageningen University & Research, Wageningen, The Netherlands
The first mechanistic details of interference by a CRISPR-Cas system were obtained by molecular analysis of the Escherichia coli system (Class-1, type-IE). In this system, five genes encode the subunits of the multi-subunit complex called Cascade [1,2]. Step-wise target binding results in a structural rearrangement of the Cascade complex, allowing for docking of the stand-alone helicase-nuclease, Cas3 [3]. While remaining bound to Cascade, Cas3 causes directed fragmentation of the non-target DNA strand [4,5]. The initial basic insights of the RNA-guided DNA interference mechanism of the type-I CRISPR-Cas system have provided the basis for genome applications, initially for the analogous DNA-targeting Class-2 systems: Cas9 and Cas12. Recently, however, also applications of the Cascade/crRNA complex have been developed, in combination with Cas3 (genome deletions) [6], with Transposons (genome insertions) [7], and with FokI-nuclease domains (generation of indels, and potentially of recombination) [8]. Moreover, Cascade-like type III CRISPR-Cas systems have recently been repurposed as sensitive diagnostics tool [9].
- Brouns, Jore et al. (2008) Science
- Jore et al. (2011) Nat Struct Mol Biol
- Wiedenheft, Lander et al. (2011) Nature
- Sinkunas et al. (2011) EMBO J, Westra et al. (2012) Mol Cell
- Künne et al. (2016) Mol Cell
- Dolan et al. (2019) Mol Cell
- Klompe et al. (2019) Nature
- Cameron et al. (2019) Nat. Biotech
- Steens, Zhou et al. (2021) Nat. Comms
The seminar will take place on the 7th of October in the Novo Nordisk Fonden building at Tuborg Havnevej 19, 2900 Hellerup. The speakers will present virtually to a live audience.
The event is free and open to all, but registration is required through this link:
Facts
Programme
