Unlike multicellular eukaryotic hosts that evolved diverse cell-types to achieve distinct biological functions and promote tasks division, unicellular organisms rely on metabolic exchange with their surrounding biotic environment. Metabolic interdependencies and cross feeding exchanges can occur and explain co-existence within complex bacterial communities. However, a key question is whether populations of genetically identical bacteria can minimize energetically costly processes by executing different metabolic tasks at the subpopulation level. DIVIDE will explore the division of labour between bacterial subpopulations of a core member of A. thaliana root microbiota – Pseudomonas brassicacearum R401 (PsR401) – a robust root colonizer that also modulates microbiota composition at the root interface. Three complementary guiding principles regarding the division of labour in PsR401 population will be explored in the DIVIDE project : (1) a transcriptional differentiation among bacterial cells rising from genetic changes within the population to promote population growth (2) a 'noisy regulation' of metabolism mediated by heterogeneous transcriptional reprogramming in bacterial cells within a clonal population (i.e. not all bacteria within the population would adjust their genome expression to the environmental constraints) (3) a division of labour in the context of the synthesis of three energetically costly metabolic compounds (iron chelators, antimicrobials, and phytotoxins) as a key mechanism to promote PsR401 persistence and competitiveness at roots. By combining a library of transposon mutants, transcriptional reporter lines, novel single cell transcriptomic approaches and microbiota reconstitution experiments in gnotobiotic plant systems, DIVIDE aims to provide a novel understanding of whether metabolic ‘coordination’ within a bacterial population is key for bacterial establishment in the root environment.

Introgression of wild alleles into cultivated tomato has been a common practice in breeding programs over the last century that has improved important traits like pathogen resistance or fruit quality. As a result, most if not all modern tomato varieties contain introgressions from a variety of wild tomato species. While the genes and functions that motivated each of the introgressions are well described, little known is known about the exact size of these introgressions, the number of genes included in them, or the existence of additional unexpected wild segments scattered throughout the genome due to incomplete backcrossing schemes. These features became evident in the only cultivated tomato reference genome sequence available, where four introgressions could be detected and one of them does not contain any known beneficial gene. Due to their large spans, introgressions from wild species can have significant unexpected consequences different from those intended when the introgressions were originally designed. Documented negative effects include suppression of recombination due to genomic rearrangements in the introgressed region or pleiotropic effects due to unfavorable genes dragged along the beneficial alleles included in the introgression. Here we propose to utilize published whole-genome information of more than 600 tomato accessions encompassing 13 different species to establish the first comprehensive catalog of wild introgressions in more than 400 tomato cultivars. To do this, we propose to first construct a tomato reference genome assembly from a cultivar that does not contain any introgressions. This new high-quality reference genome will greatly simplify the identification of non-cultivated fragments and enable the generation of a comprehensive catalog of wild introgressions in cultivated tomato based on the re-sequencing data mentioned above. The resulting catalog will allow us to select five additional cultivars displaying the most common introgressions segregating in modern tomatoes. The selected accessions will be then used to generate assemblies of their introgressions, thus greatly expanding our knowledge on the gene pool that makes modern tomatoes. Finally, we will combine novel techniques with classic genetic approaches to study the effect of the most common introgressions on the suppression of meiotic recombination and modification of transcriptional landscape of the accessions that carry them. The results of this project will not only generate major resources for future research in tomato, but will also serve as direct guidance to improve tomato cultivars by precision breeding of introgressions. Our consortium combines two groups with complementary strength including long lasting expertise in tomato genetics and evolution with experiences in high-throughput genomic data analysis and genome assembly.

Ischemic heart Failure (IHF) is a leading cause of hospitalization and mortality in Europe. This unmet challenge asks for a better understanding of the mechanisms causing myocardial tissue damage and the development of new therapeutic approaches supporting cardiac repair. The immune system plays a decisive role for initial inflammatory responses following cardiac damage and subsequent regenerative responses. However, the interplay between immune cells and cardiomyocytes/cardiac progenitor cells within the myocardium is not well understood. We aim to explore the spatial and temporal communication between cardiac myocytes, cardiac stem cells and innate immune cells during IHF. We will use high-end transcriptional profiling involving single-cell RNA-seq / tomo-seq combined with mouse genetics and large animal models to identify new factors involved in cellular interactions responsible for cardiac remodeling. Furthermore, we want to understand the function of crucial mediators of cardiomyocyte-innate immune cell interactions, the Reg-family of cytokines, for post-ischemic damage control and tissue repair. Our research will supply new approaches for the manipulation of cell-cell interactions in the failing heart. All model organisms capable of cardiac regeneration rely on immune cells to orchestrate different waves of inflammation, matrix deposition, angiogenesis and cardiomyocyte proliferation. Hence, therapeutic manipulation of local immune cell-dependent processes in the damaged heart might shift the balance between extensive scarring, minimal defect healing and regeneration.