Biology subjects

Meier, N.

Publications and source records attributed to Meier, N..

3 recordsLinked to original sources

bioRxiv2022

High efficiency multiplex biallelic heritable editing in Arabidopsis using an RNA virus

Delivery of gene editing components such as the Cas nuclease and single guide RNAs (sgRNAs) into plant cells is commonly accomplished by agrobacterium-mediated transformation. Although Arabidopsis is easy to transform, generation of biallelic edited plants requires screening a large number of plants in subsequent generations. Here, we describe optimization of the Tobacco rattle virus (TRV) for in planta delivery of sgRNAs fused to a tRNAIleu that induces efficient multiplex somatic and biallelic heritable editing in Arabidopsis. Inclusion of tRNAIleu enhances the systemic movement of TRV and the mutant phenotype is visible in the initial TRV::sgRNA-tRNAIleu infected Arabidopsis, which allows for the uncovering of lethal phenotypes. Mutant progeny are recovered in the next generation (M1) at frequencies ranging from 30-60%, with 100% mutant recovery in the following (M2) generation. TRV::tRNAIleu system described here allows generation of biallelic edited plants in a single generation and is amenable for large-scale high throughput CRISPR screens.

plant biology↗

bioRxiv2021

New fossil wasp species from the earliest Eocene Fur Formation has its closest relatives in late Eocene ambers (Hymenoptera, Ichneumonidae, Pherhombinae)

Darwin wasps (Ichneumonidae) are one of the most species-rich insect families, but also one of the most understudied ones, both in terms of their extant and extinct diversity. We here use morphometrics of wing veins and an integrative Bayesian analysis to place a new rock fossil species from the Danish Fur Formation ([~]54 Ma) in the tree of Darwin wasps. The new species, Pherhombus parvulus n. sp., is placed firmly in Pherhombinae, an extinct subfamily so far only known from Baltic and Rovno-Ukranian ambers, which are estimated to be 34-48 Ma and 34-38 Ma, respectively. Our phylogenetic analysis recovers a subfamily clade within the higher Ophioniformes formed by Pherhombinae, Townesitinae and Hybrizontinae, in accordance with previous suggestions. Due to the placement of the new species as sister to the remaining members of Pherhombinae, we argue that our finding is not at odds with a much younger, late Eocene age ([~]34-41 Ma) of Baltic amber and instead demonstrates that Pherhombus existed over a much longer period than previously thought. Our results also exemplify the power of wing vein morphometrics and integrative phylogenetic analyses in resolving the placement even of poorly preserved fossil specimens.

paleontology↗

bioRxiv2020

A common molecular mechanism for cognitive deficits and craving in alcoholism

Alcohol-dependent patients commonly show impairments in executive functions that facilitate craving and can lead to relapse. The medial prefrontal cortex, a key brain region for executive control, is prone to alcohol-induced neuroadaptations. However, the molecular mechanisms leading to executive dysfunction in alcoholism are poorly understood. Here using a bi-directional neuromodulation approach we demonstrate a causal link for reduced prefrontal mGluR2 function and both impaired executive control and alcohol craving. By neuron-specific prefrontal knockdown of mGluR2 in rats, we generated a phenotype of reduced cognitive flexibility and excessive alcohol-seeking. Conversely, restoring prefrontal mGluR2 levels in alcohol-dependent rats rescued these pathological behaviors. Also targeting mGluR2 pharmacologically reduced relapse behavior. Finally, we developed a FDG-PET biomarker to identify those individuals that respond to mGluR2-based interventions. In conclusion, we identified a common molecular pathological mechanism for both executive dysfunction and alcohol craving, and provide a personalized mGluR2-mechanism-based intervention strategy for medication development of alcoholism.

neuroscience↗