Emmy Noether Junior Research Groups

The Emmy Noether Programme of the German Research Foundation (DFG) gives exceptionally qualified early career researchers the chance to qualify for a professorship at a university by leading an independent junior research group.

Current Emmy Noether Junior Research Groups at the BMC

Research project
Nuclear Synthesis of Acyl-CoAs in the Reprogramming of Chromatin and Gene Activity
Group leader
Dr. Marta Russo
Institution
Division of Physiological Chemistry
Funding period
since 2025
Website
GEPRIS
Project description
Metabolism and gene expression, two fundamental biological processes, are strongly interconnected and collaborate to regulate cellular functions and physiological activities. Metabolic enzymes and their byproducts, the metabolites, play crucial roles in modifying chromatin structure, thereby influencing gene expression. Traditionally, scientists have primarily focused on studying metabolic pathways in cellular compartments outside the nucleus, particularly in mitochondria. However, mounting evidence suggests the presence of metabolic enzymes within the nucleus, particularly those involved in acyl-coenzyme A (acyl-CoA) metabolism, which directly impacts histone modification. Recently, I discovered the existence of three metabolic enzyme complexes in the nuclei of mammalian cells, in addition to their known location in mitochondria. Significantly, these enzyme complexes interact with the Mediator complex, an essential facilitator of gene transcription by RNA Polymerase II. I demonstrated that these nuclear enzymes retain their functionality and capacity to produce their metabolites when bound to Mediator in the nucleus, while also enriching at Mediator target genes. Consequently, their products contribute to histone modification and gene expression regulation. This discovery proposes an intriguing hypothesis: metabolic enzymes within the nucleus regulate gene expression by producing metabolites. We believe this mechanism could be particularly relevant for cells like macrophages, immune cells that swiftly adjust their gene activity upon detecting danger signals. Nevertheless, essential molecular details concerning the interplay between nuclear metabolic enzymes and the transcriptional machinery remain unclear. Hence, my objectives are: 1) to investigate the influence of these nuclear enzymes on gene regulation; 2) to identify novel protein interactions of these enzymes in the nucleus; and 3) to analyze the structure of these enzymes and their interactions with the Mediator complex. By employing advanced omics-based approaches, metabolite tracing and imaging techniques, my research aims to elucidate the functional dynamics and structural characteristics of these interactions. Macrophages will serve as the principal cellular model due to their rapid adjustments in gene expression and metabolic reprogramming in response to danger signals. In summary, the proposed research aims to provide insights into the crucial interplay between metabolism and transcriptional regulation, elucidating the role of nuclear metabolic enzymes in gene regulation.
Research project
Understanding the regulatory mechanisms governing combinatorial chromatin states
Group leader
Dr. Rodrigo Villaseñor
Institution
Division of Molecular Biology,
Biomedical Center
Funding period
since 2021
Website
GEPRIS
Project description
At the time of writing, 22 types of histone modifications have been described, including acetylation, citrullination, methylation, phosphorylation, and ubiquitination. With eight modifiable amino acid residues at about 138 positions on five canonical histone variants, more than 550 possible histone modifications have been reported. Several of these chemical marks can coexist on the same nucleosome resulting in an immense theoretical number of combinatorial possibilities. Bivalent chromatin and its associated histone modifications, H3K4me3 and H3K27me3, is perhaps the best-described example of a combinatorial chromatin state known to date. Despite years of intense research on bivalent chromatin, many fundamental questions remain unanswered. How is bivalent chromatin established and maintained in pluripotent cells? How are bivalent sites kept accessible and hence transcriptionally responsive? Are the same factors associated with bivalent chromatin in different cell types? In the first two aims of this proposal, my group will combine experimental and computational approaches to answer these fundamental questions in a quantitative and comprehensive manner. On the experimental side, my group will combine genome-wide assays with rapid protein depletion strategies to carry out mechanistic studies at unprecedented temporal control under defined conditions in mouse embryonic stem cells. In the final part of this project, we will venture into new territory. To date, only a few examples of new combinatorial chromatin states are known. However, these results open the exciting possibility for the existence of more combinatorial options in mammalian cells. In Aim3 of this project, my team will employ a robust and quantitative chromatin-proteomics approach to explore large combinatorial possibilities at single-nucleosome resolution in three distinct cell types and functionally characterize novel examples. In the future, my team will expand our chromatin-proteomics approach to other cell types and cancer cells to elucidate more combinatorial chromatin modifications.

Source: GEPRIS
Research project
Structural and functional plasticity in hippocampal networks of the young and aged brain
Group leader
Dr. Gregor Pilz
Institution
Division of Cell Biology - Anatomy III, Biomedical Center (BMC)
Funding period
since 2021
Website
GEPRIS
Project description
The dentate gyrus (DG) of the hippocampus harbors neural stem cells (NSCs) which give rise to granule cells throughout life. During this process termed adult neurogenesis adult-born neurons migrate, mature and integrate into the preexisting circuitry of the hippocampus. Adult-born neurons play a functional role in certain forms of learning and memory and levels of adult neurogenesis are altered in various neuropsychiatric diseases. A complete picture of the dynamic process of adult neurogenesis required the establishment of a technique to observe cellular lineages from NSC division to functional integration in a continuous fashion. Chronic in vivo 2 Photon imaging through a transcortical window allowed for a detailed characterization of NSC lineages as well as for measurements of neural activity in granule cells of an awake behaving animal. However, open questions on how adult-born neurons mature, integrate and in consequence alter network function in the hippocampus during behavior remain. Therefore, I will address three fundamental questions of adult neurogenesis and hippocampal function.The morphological and functional requirements for successful integration of immature neurons will be uncovered by chronic imaging over the time course of weeks after cell birth. How candidate molecular factors and physiological interventions promote maturation and integration will be tested in addition with the aim to enhance effectiveness of adult neurogenesis. Over the course of maturation and during integration adultborn neurons possess unique physiological properties and exert specific functions in the hippocampal circuit. How adult-born neurons impact information processing and memory formation in the DG – CA3 (cornuamonis region 3) circuit over the course of their integration will be investigated by direct observation of neuronal populations and simultaneous manipulation of adult-born granule cell activity. This functional testing will be carried out in a DG specific behavioral pattern separation task. Chronological aging often coincides with difficulties in the formation and retrieval of new memories. The levels of adult neurogenesis have been shown to decrease with advancing age in mammalian species. Which functional contribution lower numbers of adult generated play in hippocampal function and memory formation in aged animals remains unknown and will be addressed by a direct and chronic observational approach. If enhancing the levels of adult neurogenesis in the aged brain improves network function and memory formation will be probed by a diverse set of physiological interventions. By following these scientific aims, a more complete picture of the specific role for adult neurogenesis in function of the hippocampus will emerge.

Quelle: GEPRIS
Research project
Cooperation of autoreactive B cells and Th17 cells in the development and progression of CNS autoimmunity
Group leader
Dr. Anneli Peters
Institution
Institute of Clinical Neuroimmunology, Biomedical Center
Funding period
seit 2017
Website
GEPRIS
Themen
The goal of the proposed project is to investigate the nature of T:B cell collaboration in CNS autoimmunity taking into account the different B cell effector functions that may play a role in the pathogenesis of multiple sclerosis (MS). These include production of autoreactive antibodies, presentation of autoantigen to T cells and production of proinflammatory cytokines both in the periphery and in the CNS. To model those different B cell effector functions, we are employing and have developed different experimental autoimmune encephalomyelitis (EAE) models, each suited to answer specific questions that are still unresolved in the field: (1) Where and how do CNS-reactive B cells evolve during disease development and are disease-associated repertoire changes pathogenic? This question can be addressed in the spontaneous EAE model, the RR mouse, in which myelin-specific B cells are recruited from the endogenous repertoire and required for disease development. We could identify disease-associated changes in the repertoire in this model and can now determine the relevance of these changes for disease manifestation. (2) What functions do B and T cells fulfill in meningeal ectopic lymphoid follicles? We have established the Th17 transfer EAE model featuring large and numerous meningeal eLFs and characterized eLF B cells to be highly activated, poised for germinal center reactions, and engaged in long-lasting contacts with T cells resulting in reactivation of proinflammatory T cells in eLFs. Using our transcriptomic dataset, we are now in the unique position to determine whether similar B cell subpopulations exist in MS patients and thus gain insight into eLF function in MS. (3) What are the cellular sources of the pathogenic cytokine IL-23 and does it also have intrinsic effects on T and B cell pathogenicity? In our novel B cell-driven transfer EAE model, we found that IL-23p19 expression enhances B cell pathogenicity without affecting the T cell or myeloid response and in addition, IL-23p19 deficient T cells failed to transfer EAE. Thus, IL-23p19 may intrinsically affect T and B cell pathogenicity, in addition to the known function of APC-produced IL-23 of promoting terminal differentiation of pathogenic Th17 cells. We have generated IL-23p19fl/fl mice and can now analyze the mechanism of action of IL-23p19 in relation to cellular source in depth.

Source: GEPRIS

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