Research Topics

The evolution of Innate immunity and Antiviral systems in Animals

Viruses are everywhere. They are absolute parasites and there is no organism that does not have a virus that can infect it. Viruses are a major force in evolution and they are locked in an “arm-race” with the immune systems of their host cells. We started in May 2020 a new ERC Consolidator project called AntiViralEvo. In this project we study the evolution of antiviral systems in cnidarians, with emphasis on Anthozoa (sea anemones and corals) and their RNA—based detection and response systems. As an initial step we characterized the virome of our favorite anthozoan, Nematostella. Our first functional study of the cnidarian antiviral system was published in 2021 in MBE (see here). It unravels the evolution of the RIG-I Like Receptors (RLRs) and their function in Nematostella. You can also find popular science coverage (in Hebrew) here. Addtionally, we started in May 2021 a collaborative project (funded by BSF-NSF joint grants) with the lab of Adam Reitzel at the University of North Carolina at Charlotte where we compare the viromes and antiviral systems of different Nematostella populations to understand their evolution under ecological context.

The evolution of small RNA pathways and the roles of microRNAs in Cnidaria

MicroRNAs are small RNAs which were discovered initially in nematodes at 1993. A decade later they were also identified in most other animals and in plants and were shown to play crucial roles in the development of many species. MicroRNAs act through a protein effector complex which binds to messenger RNAs in a specific manner via annealing of the microRNA to the mRNA target and affect the target expression levels. I initialized during my postdoc in Vienna a study on the roles of microRNAs in N. vectensis development. This study is still underway but we already obtained some very exciting findings regarding the involvement of microRNAs in the regulation of expression levels of proteins involved in development of the anemone. Moreover, we have interesting results regarding the mechanism of action of microRNAs in cnidarians suggesting new and unexpected links between the microRNA pathways of plants and animals see our papers in MBE and Genome Research about this topic. This project also received much hype (and somewhat disinformative presentation!) in popular media such as here, here (in English) and here (in Hebrew). You can also read our review in Nature Ecology and Evolution here. We published in 2018 the first evidence for the role of microRNAs and piRNAs in Nematostella development and the role of methylation in stabilizing these small RNAs (see here). In 2020 we published a paper in Nature Communications deciphering the specialization of Argonaute proteins in sea anemones and corals in carrying different classes of miRNAs and siRNAs and unravelling how miRNAs are born from siRNAs in Cnidaria (see here). In 2022 we published in eLife our findings regarding a cnidarian homolog of the “plant-specific” HYL1 protein and its role in miRNA biogenesis, which puts in question the traditional evolutionary scenarios of the miRNA pathway (see here). Our latest work on miRNAs focused on the pan-cnidarian miRNA miR-2022 and revealed its function in the biogenesis of cnidocytes (the famous cnidarian stinging cells; see here).

Evolution of sea anemone (and other strange animal) toxins

This is a study I initialized as a PhD student in Tel Aviv University at the lab of Prof. Michael Gurevitz and I pursued it further in my postdoc as a side project (toxinology is a very sad addiction) and now as a PI. We published several papers about the unusual evolutionary patterns we discovered in sea anemone and scorpion toxins and speculated regarding the factors driving their selection. In general, animal toxins just like immunology-related proteins are a vast playground for strong adaptive selection as they are involved in a never-ending "arms-race" of prey and predator. We also found evidence for an unusual mode of evolution, called "concerted evolution" in the toxin genes of sea anemones. Further, we also show that the expression of neurotoxins happens in several anemone species such as Nematostella not only in nematocytes (stinging cells) but in gland cells (see here). This finding challenges the common statement presented in many invertebrate zoology textbooks that peptide cnidarian toxins are produced exclusively in nematocytes. The ecological shifts which led to toxin expression in different cell populations of closely-related species are of great interest and open the field to eco-evo studies. We also employed proteomic methods for the study of the venom components of Nematosella nematocytes and published those results.

We are taking advantage on unique tools such as transgenesis techniques that are available in Nematostella for answering questions about the evolution of venom and venom-producing cells. You can see recent examples here, here and here. You can find popular science pieces about our work from Haaretz news paper here (in Hebrew) and here (in English).

We are also fascinated by the effect of venom on organismal fitness and the ecology of animals. This is a new major direction that our lab is taking. See our latest work here and the news piece (in English) from the Jerusalem Post here.

Evolution of ION channels

Voltage-gated sodium channels are pivotal components in the conductance of neuronal signals. The unprecedented extent of sequencing of animal genomes in the last few years has enabled us to study in detail the evolution of these channels. We found that these channels have first appeared in unicellular organisms before the split of fungi and animals, but were independently lost in many lineages. Surprisingly cnidarians have a remarkable diversity of channel isoforms, but most of them cannot discern sodium from calcium and potassium. However, Cnidarians do have a selective channel isoform that evolved more than 540 million years ago in the ancestor of all extant cnidarians. The molecular basis of this selectivity is different from that found in selective sodium channels of bilaterians, indicating that sodium selectivity evolved twice independently in animals, probably in order to comply with the rising need for more complex and faster neuronal transmission. In this work we applied both electrophysiological and phylogenetic methods and a first publication came out in Cell Reports. It was followed by a review paper. Nowadays we also study the function of the DEG/ENaC channels of Nematostella. Members of this channel superfamily exhibit an extraordinary level of functional and gating diversity, leading us to wonder and investigate what might have been their original function in basally-branching animals. See our paper on the evolution of this channel superfamily and its role in sea anemones here.

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