ISTA Research Explorer (Institute of Science and Technology Austria)
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RNA-triggered Cas12a3 cleaves tRNA tails to execute bacterial immunity
No full textIn all domains of life, tRNAs mediate the transfer of genetic information from mRNAs to proteins. As their depletion suppresses translation and, consequently, viral replication, tRNAs represent long-standing and increasingly recognized targets of innate immunity1,2,3,4,5. Here we report Cas12a3 effector nucleases from type V CRISPR–Cas adaptive immune systems in bacteria that preferentially cleave tRNAs after recognition of target RNA. Cas12a3 orthologues belong to one of two previously unreported nuclease clades that exhibit RNA-mediated cleavage of non-target RNA, and are distinct from all other known type V systems. Through cell-based and biochemical assays and direct RNA sequencing, we demonstrate that recognition of a complementary target RNA by the CRISPR RNA triggers Cas12a3 to cleave the conserved 5′-CCA-3′ tail of diverse tRNAs to drive growth arrest and anti-phage defence. Cryogenic electron microscopy structures further revealed a distinct tRNA-loading domain that positions the tRNA tail in the RuvC active site of the nuclease. By designing synthetic reporters that mimic the tRNA acceptor stem and tail, we expanded the capacity of current CRISPR-based diagnostics for multiplexed RNA detection. Overall, these findings reveal widespread tRNA inactivation as a previously unrecognized CRISPR-based immune strategy that broadens the application space of the existing CRISPR toolbox
Neuroscience: What doesn’t kill you makes you stronger
No full textSmall amounts of stress are thought to have beneficial effects. A new study reports a mechanism by which the psychedelic drug, psilocybin, causes acute release of stress hormones, despite its known long-term anti-anxiety effects
Odd-Ramsey numbers of complete bipartite graphs
No full textIn his study of graph codes, Alon introduced the concept of the odd-Ramsey number of a family of graphs H in Kn, defined as the minimum number of colours needed to colour the edges of K so that every copy of a graph H E H intersects some colour class in an odd number of edges. In this paper, we focus on complete bipartite graphs. First, we completely resolve the problem when H is the family of all spanning complete bipartite graphs on n vertices. We then focus on its subfamilies, that is, {Kt,n-t : t E T} for a fixed set of integers T c [[n/2]]. We prove that the odd-Ramsey problem is equivalent to determining the maximum dimension of a linear binary code avoiding codewords of given weights, and leverage known results from coding theory to deduce asymptotically tight bounds in our setting. We conclude with bounds for the odd-Ramsey numbers of fixed (that is, non-spanning) complete bipartite subgraphs
ISTA Thesis
Full text linkMutation rates represent the net result of complex interactions among various
cellular processes and can dramatically influence the evolutionary fate of
microbial populations. However, many popular techniques used to study
mutations are subject to the confounding effects of heredity and the subtleties
of adaptation to selection, all of which make it difficult to observe any dynamic
responses of mutation rates to fitness challenges. Furthermore, in spite of the
ubiquity of quorum sensing systems across the bacterial domain and relevance
for many physiological behaviors, the effects of such mechanisms on mutation
rate and adaptation remain poorly understood. In the following work, I
present the development of a microfluidic droplet-based method to measure
single base-pair mutation rates in growing populations of the bacterium
Escherichia coli. I use this method to observe a stress-induced increase in
mutation rate that is mediated by luxS, a highly conserved bacterial quorum
sensing component. I also show that the aforementioned increase in mutation
rate, and its associated control by luxS, corresponds to a higher degree of
adaptability under competitive environments
