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Articles by Christian Iseli
Biomathematical enzyme kinetics model of prebiotic autocatalytic RNA networks: degenerating parasite-specific hyperparasite catalysts confer parasite resistance and herald the birth of molecular immunity
Abstract Catalysis and specifically autocatalysis are the quintessential building blocks of life. Yet, although autocatalytic networks are necessary, they are not sufficient for the emergence of life-like properties, such as self-propagation (replication) and adaptation. The ultimate and potentially fatal threat faced by molecular replicators is parasitism; if the polymerase error rate exceeds a critical threshold, even the fittest molecular species will disappear.
Biomathematical enzyme kinetics model of prebiotic autocatalytic RNA networks: degenerating parasite-specific hyperparasite catalysts confer parasite resistance and herald the birth of molecular immunity
Abstract The quintessential components of life comprise a potent mixture of naturally occurring, but improbable chemical reactions (catalysis), and the arrangement of such accelerated chemical reactions into closed loops (autocatalytic sets). This is required, but is not sufficient for such networks to self-propagate (amplification of the information carrier = host polymerization) and adapt (Darwinian evolution). As soon as self-propagation is attained, the next hurdle is parasitism.
DNA methylation by CcrM contributes to genome maintenance in the Agrobacterium tumefaciens plant pathogen
Abstract The cell cycle-regulated DNA methyltransferase CcrM is conserved in most Alphaproteobacteria, but its role in bacteria with complex or multicentric genomes remains unexplored. Here, we compare the methylome, the transcriptome and the phenotypes of wild-type and CcrM-depleted Agrobacterium tumefaciens cells with a dicentric genome with two essential replication origins. We find that DNA methylation has a pleiotropic impact on motility, biofilm formation and viability.
Biomathematical model of prebiotic autocatalytic RNA networks shows birth of adaptive immunity from degenerating molecular parasite catalysts
Abstract Catalysis and specifically autocatalysis are the quintessential building blocks of life. However, autocatalytic networks are necessary but not sufficient for life-like properties such as self-propagation and adaptation to emerge. We previously showed using Lotka-Volterra equations that a tripartite, early life cycle comprising a host-template, molecular parasites and hyperparasites (parasites of parasites) conferred superior stability to the habitat.
A phase 1 trial of adoptive transfer of vaccine-primed autologous circulating T cells in ovarian cancer - Nature Cancer
Abstract We have previously shown that vaccination with tumor-pulsed dendritic cells amplifies neoantigen recognition in ovarian cancer. Here, in a phase 1 clinical study (NCT01312376/UPCC26810) including 19 patients, we show that such responses are further reinvigorated by subsequent adoptive transfer of vaccine-primed, ex vivo-expanded autologous peripheral blood T cells.
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Birth of immunity in early life: stepwise emergence of resistance and immunity to complex molecular parasites via progressively degenerating hyperparasites
Abstract Autocatalytic networks likely played a central role in the shift from inanimate systems to protocells. Using an established hyperparasite framework, we model the emergence of antiparasite immunity using the Lotka Volterra equations. It builds on autocatalytic, increasingly complexed RNA networks reflecting the historical exposure to ubiquitous molecular parasites.
DNA modifications impact natural transformation of Acinetobacter baumannii
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Low number of fixed somatic mutations in a long-lived oak tree
Abstract Because plants do not possess a defined germline, deleterious somatic mutations can be passed to gametes, and a large number of cell divisions separating zygote from gamete formation may lead to many mutations in long-lived plants. We sequenced the genome of two terminal branches of a 234-year-old oak tree and found several fixed somatic single-nucleotide variants whose sequential appearance in the tree could be traced along nested sectors of younger branches.
Low Rate of Somatic Mutations in a Long-Lived Oak Tree
Low Rate of Somatic Mutations in a Long-Lived Oak Tree Namrata Sarkar, Emanuel Schmid-Siegert, Christian Iseli, Sandra Calderon, Caroline Gouhier-Darimont, Jacqueline Chrast, Pietro Cattaneo, Frederic Schutz, Laurent Farinelli, Marco Pagni, Michel Schneider, Jeremie Voumard, Michel Jaboyedoff, Christian Fankhauser, Christian S. Hardtke, Laurent Keller, John R. Pannell, Alexandre Reymond, Marc Robinson-Rechavi, Ioannis Xenarios, Philippe Reymond bioRxiv 149203; doi: https://doi.org/10.1101/149203
Cell-free DNA testing of an extended range of chromosomal anomalies: clinical experience with 6,388 consecutive cases
Overall, 258/6,388 (4.04%) samples were considered abnormal or likely abnormal (Figure 1), comprising 119 common trisomies (1.86%), 53 SCAs (0.83%), 50 RATs (0.78%), and 36 CNVs (0.56%). Conversely, 6,130 samples (95.96%) were considered normal or likely normal. Details on the sample and patient characteristics can be found in the Supplementary Results online section.
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