Portfolio of my current research projects
Origin and ancestral function of the nervous system
How did the first nervous system evolve? What were its original structure and function?
We strive to gain insights into the ancestral complexity and function of the nervous system. To address these questions, we use the evolutionary informative and experimentally accessible model - the freshwater polyp Hydra, and apply such approaches as single-cell transcriptomics, comparative genomics, functional genetics (transgenesis) and live imaging. Our findings point to a remarkable cellular and molecular complexity of the nervous system in Hydra (Klimovich et al., 2020). They also suggest that the nervous system might have emerged in the evolution in a tight interaction with the microbial environment (Klimovich & Bosch, 2018). We provide evidence that the ancestral pacemaker neurons emerged as immunocompetent cells that directly interact with the commensal microbiota. Other neurons, such as the ones involved in the eating behaviour, have also evolved in a dialogue with the microbiome (Giez et al., 2023). Currently, we are deciphering the molecular mechanisms underlying this cross-talk. These efforts will provide insights into the fundamental principles of neuronal circuits architecture and function.
Architecture, activity and plasticity of simple nervous systems
How do individual neurons form a nervous system?
How is the nervous system of the non-senescent Hydra dynamically maintained?
We are interested in uncovering the fundamental principles of neuronal network topology, activity, plasticity, and energy efficiency. To this end, we combine experimentation on Hydra with computational modelling approaches. This project is a part of the Collaborative Research Center 1461 "Neurotronics: Bio-inspired Information Pathways" funded by the German Science Foundation (DFG). In our experiments, we extensively use in vivo imaging of the neuronal network dynamics and explore the proliferation and migration of neuronal precursors, differentiation of neurons, emergence of their connectivity and activity, and the neuronal death. Together with the group of Prof. Claus Hilgetag (UKE, Hamburg), we develop computational models of network topology and activity to explore how developmental constraints and basic plasticity rules lead to emergence of complex activity patterns and behaviours. These efforts will not only enrich our understanding of the uniquely dynamic nervous system of Hydra, but will also inform about the fundamental rules of neuronal network architecture and plasticity.
Evolutionary role of taxonomically-restricted genes
Non-conserved genes are abundant in the genome of every animal. In Hydra, taxonomically-restricted
genes represent about 40% of its genome. What is the developmental role of these genes?
Recently, we uncovered a surprising abundance and diversity of transcripts encoded in taxonomically-restricted genes (TRGs) in Hydra neurons. Using comparative genomics, machine learning, and transgenesis approaches we investigate what role do these cnidarian- and even Hydra-specific genes play. Our findings suggest that these genes play a crucial role in individualisation of neuronal types, their maturation and non-random wiring. This project is supported by a grant from the German Research Foundation (DFG).
Evolutionary roots of tumor formation
How old are tumors? Are all animals capable of developing tumors? We have provided the first evidence for naturally occurring tumors in two Hydra species (Domazet-Loso, Klimovich et al., 2014). This study suggests that tumor formation is as old as multicellularity. In this project, we join efforts with Tomislav Domazet-Loso (Ruder Boskovic Institute, Zagreb).
Recently, we demonstrated that the tumor development in Hydra is caused by an interaction between an environmental bacterium Turneriella and the Hydra-associated resident Pseudomonas bacterium (Rathje et al., 2020). We continue exploring the evolutionary and ecological implications of tumor formation in collaboration with Frédéric Thomas at CREEC, Montpellier (Boutry et al., 2023; Boutry et al., 2022).
Transgenesis in Hydra
Developmental studies on Hydra rely on in vivo tracing of cells and on the functional analysis of genes by transgenesis. To leverage the power of this model, we implement the previously developed tools and develop new approaches for transgenesis in Hydra. We have developed the first inducible gene expression system in Hydra (Klimovich et al., 2019) and created a collection of transgenic lines for Ca-imaging of individual neuronal populations (Giez et al., 2023). Recently, we also developed a versatile transgenesis system for selective cell ablation in Hydra (Giez et al., 2023). With Jörg Wittlieb, we operate the Transgenic Hydra Facility in Kiel University (www.transgenic-hydra.org) and thereby provide access of the community to the transgenesis technology.