ABOUT

Despite numerous scientific breakthroughs, society is still facing global health challenges. Most diseases show complex symptomatic patterns that are orchestrated by overarching signaling pathways and driven by mechanisms such as inflammation, which are extremely difficult to identify and to understand. Within ENABLE, we strive to unravel and understand selected pathogenic mechanisms and signaling pathways to identify disease-relevant critical targets for therapeutic intervention. We will focus on three closely interconnected areas that impact on a broad range of diseases:

Dysregulation of cellular homeostasis drives diseases such as cancer and immunological disorders. We aim to investigate the molecular and spatial organization of the major pathways, focusing on their crosstalk and induction of cell death and inflammation. Understanding molecular host-pathogen interactions during infection is one of the most challenging aspects of searching for new therapeutic strategies to treat infections. We will focus on understanding the invasion mechanisms of bacteria and viruses into host cells and study the pathogenic effects of microbial toxins or virulence factors. Dissection of inflammatory signaling pathways is the key to identify crucial mediators and effectors of inflammatory processes in the human body. We will investigate mechanistic details of immune activation and processes underlying the inflammatory milieu in different pathologic conditions.

ENABLE is built on the already existing strong research networks and technology platforms at Goethe University Frankfurt, the MPI of Biophysics, the Georg-Speyer-Haus, the FIAS and the Fraunhofer ITMP. To approach the highly challenging scientific questions, we will implement novel technologies and tools, especially chemical probes and biologics, which can be used to interfere with cellular functions to a hitherto unknown level of specificity and therefore dissect regulatory networks with high precision.

NEWS

24 Mar 2025 - 4th Frankfurt Conference on Quality Control in Life Processes

Registration open!

ENABLE and SFB 1177 are organizing the 4th Frankfurt Conference on Quality Control in Life Processes (FCQC) which will take place from March 24th – 27th 2025 at Campus Westend of Goethe University Frankfurt.

The conference aims to accelerate our understanding of quality control pathways and their interconnectivity and to utilize this knowledge for the improved treatment of human diseases. It will feature interdisciplinary sessions that cover topics including quality control mechanisms and networks, the interplay between autophagy and ubiquitin in health and disease and emerging therapeutics utilizing the ubiquitin system.

For information about speakers and registration, please visit the conference website.

Organizers: Ivan Đikić, Maike Windbergs & Volker Dötsch

Conference managers: Julia Lau (SFB1177) & Laura Spindler (ENABLE)

FCQC@uni-frankfurt.de

05 Dec 2024 - 1st Symposium on Advances in Therapeutic Approaches

The three alliances ENABLE, PROXIDRUGS and TheraNova are organizing the 1st Symposium on Advances in Therapeutic Approaches. The event will take place from December 5th - 6th at Campus Westend of Goethe University Frankfurt. The thematic focus will be on targeted protein degradation, technology advances, delivery, RNA therapeutics and common mechanisms of human diseases.

For information about speakers and registration, please visit the symposium website.

The event will also be used as the final event of the ENABLE clusterproject. All ENABLE members (group leaders, postdocs & PhD candidates) are asked to attend.

20 Sep 2024 - Very early-career scientists discover the cell together with ENABLE PI Anja Bremm

On 20th September, it was World Children’s Day in Germany and ENABLE PI Anja Bremm took the opportunity to transfer her enthusiasm for science to young children. It was an exciting afternoon on the banks of beautiful river Mosel in Traben-Trarbach, with many very early-career scientists gaining first pipetting experience, being amazed at how little a microliter is. 3D models and fluorescent images provided an illustration of what cells look like, and craft lovers were in their element by cutting out cell organelles.

22 Aug 2024 - PROXIDRUGS Cluster4Future funded for a further three years

news image

Irina Bezsonova


The PROXIDRUGS consortium was successfully evaluated by an independent jury and will be funded by the Federal Ministry of Education and Research (BMBF) as part of Clusters4Future initiative with up to €15 million over the next three years, starting in January 2025. PROXIDRUGS, one of seven initially successful clusters, is thus entering its second implementation phase. A primary aim of the Clusters4Future initiative is to accelerate the transfer of basic research into application.

The consortium continues to focus on research into the innovative drug class of proximity-inducing agents, so-called “proxidrugs”, by advancing required technologies and using these to develop new therapeutic strategies. “Proxidrugs” use the cell's own waste management system to degrade disease-relevant proteins in a highly specified manner. They have the potential to target 80 percent of disease-relevant proteins that have thus far been deemed as undruggable with traditional small molecules.

ENABLE speaker Ivan Đikić explains: “During the last three years we have made great progress advancing technologies and establishing new platforms that can be used to identify the building blocks for proxidrugs. These technology platforms will now be systematically developed further. We have also strategically expanded the PROXIDRUGS network, integrating numerous partners from the biotech and pharmaceutical sectors, who will contribute their specific expertise to transfer findings to medical application.”

PROXIDRUGS was established in 2021 as a regional network of nine partners from academia and industry. The network covers the entire value chain from basic research to clinical application. During the second implementation phase, 21 partners will work together on ten interdisciplinary projects, all of which are positioned in the pre-competitive space. “In preparation for the second implementation phase, it was our goal to integrate more small and medium-sized companies, alongside large pharmaceutical companies, which can strengthen the consortium in relevant areas such as structure elucidation, chemical synthesis, substance libraries and artificial intelligence. We are delighted that we were able to achieve this goal and attract some highly relevant partners,” explains Dr. Kerstin Koch, Head of the Cluster Office at the Goethe University Frankfurt.

During the first implementation phase, the course was set for the cluster’s longterm success: Through an official association with “House of Pharma & Healthcare”, the cluster aims to sustain its cluster management beyond the potential three implementation phases of the Clusters4Future initiative. Additionally, the innovation hub “Frankfurt Competence Center for Emerging Therapeutics” (FCET) was founded at the Goethe University. It bundles important technology platforms and makes them available to all existing cluster partners. In future, the FCET will also be able to offer services for external scientists and companies.

31 May 2024 - Funding decision for Collaborative Research Centre “UbiCancer” (CRC/TRR 387)

Today, the German Research Foundation (DFG) announced that the transregional CRC on functionalisation of the ubiquitin system against cancer (UbiQancer) will be funded with € 18 M for the next four years. The CRC/TRR is coordinated by Technical University Munich (speaker: Prof. Florian Bassermann) with Goethe University Frankfurt and Julius-Maximilians-Universität Würzburg as co-applicant universities, and Universities of Kiel and Mainz, Helmholtz Munich, and the MPI of Biochemistry in Martinsried being involved as partners.

The CRC/TRR aims to develop innovative therapeutic strategies by a better understanding of the role of protein ubiquitination in cancer. Scientists within the network wish to gain a mechanistic understanding of aberrant ubiquitin-dependent processes in specific tumour types: AML, B-cell neoplasms, non-small cell lung cancer and colorectal cancer. The CRC/TRR strives to establish a comprehensive exploratory hub for the discovery and functionalization of relevant vulnerabilities, and to seize this knowledge for the development of compounds against validated ubiquitin-related targets and the development of PROTACs (proteolysis targeting chimera) against oncoproteins that evade direct inhibition.

From Frankfurt side, IBC2 Directors Ivan Đikić and Stefan Müller have been heavily involved in conceptualizing the program. “In Frankfurt, the foundation for establishing this CRC/TRR was laid by the HMWK-funded LOEWE project Ub-Net”, explains Ivan Đikić. “The LOEWE network not only enabled us to generate relevant foundational data, but also kicked off the establishment of technological platforms which have become critical for projects within the CRC/TRR.”. Ivan Đikić represents Frankfurt together with Christian Münch, Director of the Institute of Systems Medicine, in the CRC/TRR’s steering board. Besides Đikić, Müller and Münch, ENABLE scientists Anja Bremm, Alexandra Stolz and Stefan Knapp are participating.

17 Jul 2023 - ENABLE & CRC 1177 IRTG retreat

PhD candidates and Postdocs of the two consortia ENABLE and CRC 1177 met in Koblenz this week to present and discuss their research results on cellular homeostasis, infection, inflammation and autophagy. The scientific program was flanked by the workshops “Motherhood in science”, given by Dr. Lena Eckert – Netzwerk Motherhood and Science, and “Job entry and career path in industry” by Dr. Lisa Steinhauser, and rounded off by evening activities such as the hike to and visit of Fort Ehrenbreitstein during sunset.

IRTG members Anshu Khatri (Dötsch lab), Pascale Henning-Domres (Kern lab) and Ramya Lakshmana Iyer (Bremm lab) took over the organization of the retreat in addition to their responsibilities as PhD candidates. Many thanks for the inspiring and well organized networking event!

26 Apr 2022 - Three ENABLE researchers successful in ERC Advanced Grant competition.

ENABLE researchers were exceptionally successful in the ERC Advanced Grant competition. Martin Beck (MPI of Biophysics), Ivan Đikić and Stefanie Dimmeler (both Goethe University) all won one of the prestigious grants that come along with research funding in the amount of € 2.5 million for the next five years. For Stefanie Dimmeler and Ivan Đikić it is already the third time that they receive the ERC Advanced Grant, Martin Beck has previously been awarded with both an ERC Starting and an ERC Consolidator Grant. The three projects are tackling highly relevant and challenging mechanistic questions in the biomedical space:

NPCvalve (Martin Beck): Nuclear pores enable transport of macromolecules between the cytoplasm and the nucleus. Recent findings indicate that there may be more functions beyond nucleocytoplasmic transport. In his project, Martin Beck plans to tackle the hypothesis that nuclear pores may act as self-regulating valves for flux across the nuclear envelope. The results of this research will contribute to a better understanding of how cells deal with acute mechanical stress and reveal new therapeutic options for diseases.

Neuroheart (Stefanie Dimmeler): Ageing has long been known as major risk factor for cardiovascular disease, although the mechanisms underlying age-related changes are far from being understood. Preliminary data show that senescence goes along with a reduction in cardiac innervation. In her project, Stefanie Dimmeler plans to reveal how the crosstalk between neuronal and vascular cells impact on maintaining a healthy heart.

ER-REMODEL (Ivan Đikić): As the largest intracellular membrane system, the ER covers important functions in numerous processes. To fulfill its diverse tasks, the ER is constantly adapting its shape. Within his project, Ivan Đikić will explore how ER-phagy pathways are driving the entire process of membrane remodelling. The emerging data will not only provide new insights into organelle dynamics, but will also help to understand the impact of ER and ER-phagy on neurodegenerative diseases, cancer and infections.

Besides tackling highly challenging questions in the field, all three projects are characterized by utilizing a combination of highly sophisticated technologies, generating unprecedented insights not only on the structural, molecular and cellular level, but also utilizing state-of-the-art bioinformatics and modelling. The results of all three are expected to aid the development of novel therapeutic strategies, which is the core aim of ENABLE and also in the focus of the initiative EMTHERA, which follows on ENABLE as a joint endeavor of Frankfurt and Mainz scientists for the next round of the federal excellence strategy.

21 Sep 2021 - Impressive talks and fruitful discussion during the first EnABLE kick off meeting in Glashütten

From September 19th to 20th 2021, the EnABLE kick-off meeting took place, gathering more than 40 scientists in a highly interdisciplinary environment spanning from computational modelling, medicinal chemistry over to clinical infectiology and economics. Filled with impressive talks and intensive exchange, these two days marked another successful milestone in the strive of EnABLE to unravel and understand selected pathogenic mechanisms and signaling pathways to identify disease-relevant critical targets for therapeutic intervention in the areas of dysregulated celluar homeostasis, infections and inflammation.

18 Aug 2021 - Otto Meyerhof Award 2021 goes to Christian Münch

Christian Münch, group leader at the IBC2, will receive the Otto Meyerhof Award 2021 by the German Society for Biochemistry and Molecular Biology (GBM). The award honours the outstanding research performance of young investigators under 40. The research of the Münch group focuses on the elucidation of cellular stress responses upon protein misfolding and as a consequence of disease-causing mutations and infections, building on Münch’s in-depth expertise in quantitative mass spectrometry and system biology approaches. To quantitatively measure small changes in protein translation, the group developed a new analytical method called multiplexed enhanced protein dynamics (mePROD) proteomics. This approach has helped to study the effects of mTOR inhibition and integrated stress response activation (Klann et al., Mol Cell 2020). It is broadly adaptable to very different research questions, as very successfully shown by Münch and his team after onset of the corona pandemic: Within a matter of a few weeks, they were able to determine host cell responses to SARS-CoV-2 infection (Bojkova et al., Nature 2020) providing important insights into changes imposed by the virus upon host cells. Further analyses revealed cellular pathways that are crucial for SARS-CoV-2 replication in cells (Klann et al., Mol Cell 2020) These studies pointed to new therapeutic targets that are now under clinical evaluation or approved for the treatment of COVID-19 patients.

The Otto Meyerhof Award is endowed with 5,000 Euros, funded by Boehringer Ingelheim Pharma. The prize ceremony will take place virtually on the 16th of September, with Christian Münch presenting the award lecture on „Dynamic protein synthesis changes in stress and disease”. For those wishing to attend the event, registration until the 14th of September is required:  https://gbm-online.de/gbm-awards-event.html.

01 Feb 2021 - The State of Hesse funds research network on inflammation and infection

As announced today, Frankfurt scientists were successful in securing funding for the ENABLE cluster project which aims at identifying disease-relevant key targets and enabling innovative therapeutic strategies. For the next four years, the project will be supported with 8 M€ by the State of Hesse as part of the cluster initiative to prepare for the next round of the federal Excellence Strategy. The ENABLE research program is centered around inflammation, infection and cellular homeostasis, which are all impacting on a broad range of diseases, many of them with high unmet medical need. It relies on innovative technologies and close team work between basic and translational research. 

“This generous financial support will enable us to utilize modern tools, such as chemical probes and biologics, for a new wave of translational drug discovery”, said Ivan Đikić from the Institute of Biochemistry II on Niederrad Campus, who shares the spokesperson responsibility with Maike Windbergs from the Institute of Pharmaceutical Technology at the Riedberg Campus. Windbergs added: “These tools enable us to interfere with cellular functions at a hitherto unknown level of specificity and will help us to gain a more precise insight into inflammation processes which determine the outcome of many diseases.”

The success of this integrated translational research is based on the participation of scientists from five faculties at Goethe University and partners such as the Max Planck Institute of Biophysics, the Fraunhofer Institute for Translational Medicine and Pharmacology, the Frankfurt Institute for Advanced Studies (FIAS) and the Georg Speyer Haus (GSH). The future plan for ENABLE is to compete for a Cluster of Excellence within the next round of the federal Excellence Strategy. 

PROJECTS

Area A - Cellular Homeostasis

Dr. Martin Beck

Max Planck Institute of Biophysics
Max-von-Laue-Straße 3
60438 Frankfurt am Main

Martin.Beck@biophys.mpg.de
Tel.: +49 69 6303 3500
Beck group

Functional cellular modules have often been characterised in vitro. However, relatively little is known about their interplay and spatio-temporal arrangement in the context of living cells, i.e. their 'molecular sociology'. We use integrative, in situ structural biology techniques to study the structure, function and assembly of very large macromolecular complexes in their native environment. We rely on a diverse methodological repertoire, including cryo-EM, structural proteomics, biochemistry, imaging, animal model systems and computational modeling (Robinson et al., 2007; Beck and Baumeister, 2016). Our contribution to research within the ENABLE consortium aims to understand the mechanisms of nuclear envelope and nuclear pore complex quality control.

Dr. Anja Bremm

Institute of Biochemistry II
Goethe University Frankfurt
Theodor-Stern-Kai 7
60590 Frankfurt am Main

bremm@em.uni-frankfurt.de
Tel.: +49 69 6301 5450
Bremm group

Our research group investigates the role of the ubiquitin system in selective autophagy and in cellular responses to hypoxia or oxidative stress. Protein ubiquitination has two major consequences: control of protein turnover by providing proteasomal and lysosomal targeting signals and governance of cell signalling networks by regulation of protein interactions and activities. We are particularly interested in deubiquitinases (DUBs), the enzymes that release conjugated ubiquitin from proteins and that maintain the dynamic state of the cellular ubiquitinome. Altered DUB activity is associated with a multitude of pathologies and DUBs represent promising novel structures for targeted therapy. Within ENABLE, we aim to increase our understanding of the physiological functions and control mechanisms of DUBs and how they contribute to cellular homeostasis. 

Prof. Dr. Volker Dötsch

Institute of Biophysical Chemistry
Goethe University Frankfurt
Max-von-Laue Straße 9
60438 Frankfurt am Main

vdoetsch@em.uni-frankfurt.de
Tel.: +49 69 798 29631
Dötsch group

Our laboratory focuses on structural and functional investigations of important biological macromolecules involved in different quality control systems. Projects include the characterization of the oocytes and stem cell quality control factor p63 that also plays essential roles as a master regulator of chromatin structure in epithelial stem cells. We investigate the structure of different active and inactive conformations of p63 as well as its interactions with other proteins such as kinases and E3 ligases. We further study the interaction and function of p53 isoforms as well as the properties of p53 mutants. In addition, we focus on the structural and functional characterization of proteins involved in apoptosis and autophagy, in particular interaction of E2 and E3 enzymes involved in the ERAD process and the function of members of the Atg8 protein family in autophagy and non-autophagy related functions such as ufmylation. We use a combination of several biophysical techniques including x-ray crystallography, NMR spectroscopy and ITC with biochemical assays, cell culture experiments and mouse tissue culture.

Prof. Stefan Knapp, Ph.D.

Institute for Pharmaceutical Chemistry
Goethe University Frankfurt
Max-von-Laue-Straße 9
Frankfurt am Main

Knapp@pharmchem.uni-frankfurt.de
Tel: +49 69 798 42079
Knapp group

Our research group is interested in using high resolution structural information for the design of selective chemical inhibitors, so called chemical probes. Chemical probes are versatile tools that can be used to study complex biological systems and also to evaluate a protein as a target for drug development. We will support ENABLE by providing bespoke chemical probe collections for signalling pathways of interest as well as developing and characterizing new chemical probes in collaboration with ENABLE scientists. Specifically, we are for instance collaborating with the Dötsch laboratory on targeting the protein kinase CK1, with the Lecaudey laboratory on chemical tools modulating Hippo signalling and with the Müller-McNicoll group on targeting kinases that regulate RNA splicing.

Prof. Michaela Müller-McNicoll, Ph.D.

Institute for Molecular Biosciences

Goethe University Frankfurt

Max-von-Laue-Straße 13

Frankfurt am Main

Mueller-McNicoll@bio.uni-frankfurt.de
Tel: +49 69 798 42079
Müller-McNicoll group
Prof. Dr. Stefan Müller

Institute of Biochemistry II
Goethe University Frankfurt
Theodor-Stern-Kai 7
60590 Frankfurt am Main

ste.mueller@em.uni-frankfurt.de
Tel.: +49 69 6301 83647
Müller group

In the joint ENABLE project with Stefan Müller, I will investigate a) how SUMO conjugation-deconjugation networks and kinase-phosphatase systems affect the dynamics and interplay of membrane-less organelles (MLOs), including stress granules, PML nuclear bodies, nuclear speckles and paraspeckles, b) how RNA-protein interactions are affected by changes in SUMOylation and phosphorylation in response to cellular stress e.g. proteotoxic stress, splicing stress or hypoxia, and c) how these pathways can be targeted by small molecules or biologics to modulate MLO dynamics and potentially interfere with altered MLO dynamics in human disease.

Area B - Infection

Prof. Dr. med. Sandra Ciesek, MHBA

Institute of Medical Virology
Goethe University Frankfurt
Paul-Ehrlich-Str. 40
60590 Frankfurt am Main

sandra.ciesek@kgu.de
Tel.: +49 69 6301 5219
Ciesek group

Our institute has many years of experience in establishing cell culture models for RNA viruses. One focus is the identification and characterization of new host factors that could then be used as antiviral targets. Our previous studies of changes in Caco-2 cells upon SARS-CoV-2 infection discovered a range of pathways essential for SARS-CoV-2 replication and revealed modulation of cellular PQC machineries and pathways involved in inflammation responses. 

Within ENABLE, we will extend these analyses to gain a better understanding of SARS-CoV-2. The knowledge of cellular PQC machineries and identification of new host factors is critical for the discovery of new antiviral strategies. There are no specific antiviral therapies for viral diseases including other common cold corona-viruses and hepatitis E virus (HEV). HEV is in this context of special interest since it, similar to SARS-CoV-2, can infect the nervous system, frequently leading to neurological disorders, such as Guillain-Barre-syndrome. We will compare our findings to profiles of other common cold coronaviruses (e.g. OC43, 229E) and HEV infection acquired in the same manner. In addition, we will perform translatome proteomics in lung cell lines (e.g. A549) infected with SARS-CoV-2 or other common coronaviruses to investigate the similarities and differences between these viruses.

Prof. Ivan Đikić, MD, Ph.D.

Institute of Biochemistry II
Goethe University Frankfurt   
Theodor-Stern-Kai 7
60590 Frankfurt am Main

dikic@biochem2.uni-frankfurt.de
Tel.: +49 69 6301 5652
Đikić group

Our laboratory focuses on studying molecular mechanisms of the two major degradation pathways – the ubiquitin-proteasome system (UPS) and autophagy. Degradation of cellular components, either through the UPS or the lysosome (autophagy), is essential for maintaining cellular homeostasis. Disruption to either of the processes can lead to neurodegenerative diseases, cancer and other pathologies.

Within ENABLE, we focus on (i) a better understanding of quality control of organelle (ER, mitochondria, nuclear envelope) morphpology and functions as well as the cross-talk in molecular pathways that impact on stress conditions including inflammation and disease-based causes and we will increase our understanding why certain proteins/pathways are targeted by pathogens. (ii) We will assess the role of ER-phagy during SARS-CoV-2 infection and determine the effects of ER-phagy perturbation on SARS-CoV-2 replication. In addition, we will determine the influence of bacterial virulence factors on innate immune and inflammatory responses and evaluate unique and common pathways by which different bacteria (Legionella pneumophilia, Salmonella enterica, Acinetobacter baumanii) modulate organelle function, morphology and cellular homeostasis. (iii) We will explore the role of inflammation in intercellular and cell-matrix interactions of the tumor microenvironment.

Christian Münch, Ph.D.

Institute of Biochemistry II
Goethe University Frankfurt
Theodor-Stern-Kai 7
60590 Frankfurt am Main

ch.muench@em.uni-frankfurt.de
Tel.: +49 69 6301 3715
Münch group

Our laboratory focuses on understanding changes in cell homeostasis upon perturbation. How do cells respond to stress derived from protein misfolding, disease, or infection? How do these processes affect the different cellular compartments? We try to obtain holistic understanding of the resulting cellular changes by using molecular systems biology approaches with a major focus on time-resolved proteomics.

Within ENABLE, we will focus on i) the connection between protein quality control mechanisms guiding the response to protein misfolding in the cytosol, mitochondria, and the ER. Important aspects are unfolded protein responses, protein degradation, and the connection to cellular inflammation pathways. ii) Systems medicine characterization of cell host responses to infection with coronaviruses. We will investigate common features and virus-specific properties. Ultimately, we aim to span these two areas to understand the role of protein quality control mechanisms across stresses.

Prof. Dr. Maike Windbergs

Institute of Pharmaceutical Technology and
Buchmann Institute for Molecular Life Sciences
Goethe University Frankfurt 
Max-von-Laue-Str. 15
60438 Frankfurt am Main

windbergs@em.uni-frankfurt.de
+49 69 798 42715
Windbergs group

Our research group strives to explore and understand complex disease patterns governing infection and inflammation in the human body with the overarching aim to develop novel therapeutic approaches for the effective treatment of inflammatory and infectious diseases. At the interface between life sciences and engineering, we combine our expertise in 3D human derived in vitro models and advanced label-free imaging technologies to dissect signalling pathways and unravel selected physiological and pathophysiological processes in human tissue. Further, we design innovative biomimetic drug delivery systems which allow for targeted application of novel actives and investigate their interaction with human cells and tissues as well as their therapeutic effect. 

Within ENABLE, we will work in close collaboration with multiple other projects across different areas. We will use our expertise in cultivating physiologically-relevant in vitro models of different biological barriers in the human body to investigate inflammatory machineries in response to SARS-CoV-2 infection in the lung and the effects of bacterial infections in the human intestine (Area B ‘Infection’). We will further investigate the human intestinal epithelium in response to different pathological states (e.g. inflammatory bowel disease and systemic inflammation) to understand overarching inflammatory pathways in order to identify novel targets and to evaluate the potential of novel actives (Area C ‘Inflammation’). In order to establish a deeper understanding of cell-cell and cell-matrix interactions in the tumor microenvironment, we will design tailor-made extracellular matrices as scaffolds for the cultivation of three-dimensional cancer tissue models. The implementation of label-free confocal Raman microscopy across different projects enables us to gain novel insights into the interactions of cells with their environment as well as with novel actives in a non-invasive and yet chemically-selective imaging approach.

Area C - Inflammation

Prof. Dr. Stefanie Dimmeler

Institute of Cardiovascular Regeneration
Goethe University Frankfurt
Theodor-Stern-Kai 7
60590 Frankfurt am Main

dimmeler@em.uni-frankfurt.de
Tel.: +49 69 6301 6667
Institute of Cardiovascular Regeneration

In ENABLE, we plan to dissect the role of mutations leading to clonal hematopoiesis of indetermined potential (CHIP) in the inflammatory response. Mutations in the epigenetic regulators TET2 or DNMT3A but also in various other genes can lead to the expansion of hematopoietic stems and are associated with a higher incidence of cardiovascular disease. Our own recent studies further demonstrate a worsening of prognosis in CHIP mutant carrying heart failure patients or patients with aortic stenosis. I this project, we now have the following aims: 1) Characterize the impact of mutations in TET2 and DNMT3A driver genes on the transcriptome of monocytes, 2) Identify druggable targets and develop small molecules that interfere with the increased inflammatory signatures of TET2 or DNMT3A mutant carrying hematopoietic cells, and 3) Test therapeutic strategies to reduce CHIP-associated inflammatory burden.

Prof. Dr. Dr. Gerd Geisslinger

Institute for Clinical Pharmacology
Goethe University Frankfurt and
Fraunhofer Institute for Translational Medicine and Pharmacology
Theodor-Stern-Kai 7
60590 Frankfurt am Main

geisslinger@em.uni-frankfurt.de
PD Dr. Aimo Kannt

Fraunhofer Institute for Translational Medicine and Pharmacology
Industriepark Hoechst, G879
65926 Frankfurt am Main

aimo.kannt@itmp.fraunhofer.de
Tel.: +49 173 6895149
Fraunhofer ITMP

Chronic inflammation and excessive inflammatory responses to tissue injury or infection are important underlying or exacerbating factors of a broad spectrum of disorders. Forward translational approaches to understand the molecular underpinnings of inflammatory contributions to pathogenesis have often failed due to inter-species differences in the molecular components of the immune system, e.g. between rodents and humans, and results from animal models often could not be confirmed in clinical settings.

Within ENABLE, we are following an approach of reverse translation: Samples from patients with immune-inflammatory disorders or acute inflammatory responses, available through the Fraunhofer 4D Inflammation Clinic, will be analyzed using multi-omics technologies, systems biology, network analysis and machine learning to identify characteristic molecular signatures of disease, new biomarkers that predict disease trajectories, or new targets for pharmacological intervention.

Prof. Dr. med. Daniela Krause

Georg-Speyer-Haus and Goethe University Frankfurt

Paul-Ehrlich-Straße 42-44

60596 Frankfurt am Main

Krause@gsh.uni-frankfurt.de
Tel.: +49 69 63395 500
Krause group

Approximately 40% of men and women will be diagnosed with cancer at some point during their lifetimes. Given the ageing of the population in the developed world, the incidence of cancer is expected to increase.

Therefore, this project will explore the role of inflammation in intercellular and cell-matrix interactions of the tumor microenvironment and target hypoxia- and inflammation-mediating pathways for validation and identification of novel targets in various cancers. Our goals are to a) understand cell-cell and cell-matrix interactions in the tumor microenvironment in hypoxic and inflammatory conditions, b) target hypoxia- and inflammation-mediating pathways with chemical probes or biologics and c) validate the discovered targets and identify new targets in various cancer entities. Our highly collaborative studies will include innovative technologies such as proteomics, high resolution microscopy, artificial scaffolds, computational modeling and many others to drive forward our goal of understanding cancer more completely.

Prof. Dr. Virginie Lecaudey

Institute for Cell Biology and Neuroscience
Goethe-Universität Frankfurt
Max-von-Laue-Straße 13
60438 Frankfurt am Main

lecaudey@bio.uni-frankfurt.de
Tel.: +49 69 798 42102
Lecaudey group

Our lab is interested in understanding how cells coordinate different biological processes including proliferation, migration, cell shape changes and cell fate acquisition to form functional organs during embryonic development. For this, we use the zebrafish embryo as an in vivo model and combine gain- and loss-of-function analyses with modern live imaging techniques. Recently, we have been focusing on the role of the Hippo signalling pathway in proliferation control and cell migration during embryonic development, and on the role of Integrin-based cell-substrate adhesion in collective migration.
Within ENABLE, we will (i) focus on the role of Hippo signalling in tissue homeostasis, in particular we will analyse cross-interactions between Hippo and the p53 family of proteins and (ii) dissect the interplay between stress granule formation and inflammation in healthy and disease state. We will combine mutants and transgenic lines analysis to high-resolution live-imaging and develop and validate small molecule inhibitors and DARPins in our in vivo model.   

PD Dr. Christoph Welsch, MD

Department of Internal Medicine I

Goethe University Frankfurt

Theodor-Stern-Kai 7

60590 Frankfurt

christoph.welsch@kgu.de
Tel.: +49 69 6301 4840
Welsch group

Acute-on-chronic liver failure (ACLF) is defined by organ failure in patients with acute decompensated cirrhosis and is associated with tremendously high short-term mortality. Our studies have shown that systemic inflammation, especially driven by bacterial translocation and/or inflammasomes activation, is the key mechanism inducing organ failure not only of the liver, but also in extrahepatic organs (especially kidney and brain) in ACLF. However, it remains unclear how systemic inflammation induces organ dysfunction and failure via the inflammasomes activation.

We will investigate the molecular pathways underlying the activation of liver inflammation with focus on the inflammasome that leads to the disruption of the gut barrier and, as a consequence, to systemic inflammation and organ failure of liver and kidney. Inflammasome activation in the liver and organ failure will be analysed by in vivo models of NLRP-3, ASC and Caspase-1 deficient and WT mice after induction of ACLF by lipopolysaccharides (LPS), and confirmed in human tissue.

Prof. Dr. Maike Windbergs

Institute of Pharmaceutical Technology and
Buchmann Institute for Molecular Life Sciences
Goethe University Frankfurt 
Max-von-Laue-Str. 15
60438 Frankfurt am Main

windbergs@em.uni-frankfurt.de
+49 69 798 42715
Windbergs group

Our research group strives to explore and understand complex disease patterns governing infection and inflammation in the human body with the overarching aim to develop novel therapeutic approaches for the effective treatment of inflammatory and infectious diseases. At the interface between life sciences and engineering, we combine our expertise in 3D human derived in vitro models and advanced label-free imaging technologies to dissect signalling pathways and unravel selected physiological and pathophysiological processes in human tissue. Further, we design innovative biomimetic drug delivery systems which allow for targeted application of novel actives and investigate their interaction with human cells and tissues as well as their therapeutic effect. 

Within ENABLE, we will work in close collaboration with multiple other projects across different areas. We will use our expertise in cultivating physiologically-relevant in vitro models of different biological barriers in the human body to investigate inflammatory machineries in response to SARS-CoV-2 infection in the lung and the effects of bacterial infections in the human intestine (Area B ‘Infection’). We will further investigate the human intestinal epithelium in response to different pathological states (e.g. inflammatory bowel disease and systemic inflammation) to understand overarching inflammatory pathways in order to identify novel targets and to evaluate the potential of novel actives (Area C ‘Inflammation’). In order to establish a deeper understanding of cell-cell and cell-matrix interactions in the tumor microenvironment, we will design tailor-made extracellular matrices as scaffolds for the cultivation of three-dimensional cancer tissue models. The implementation of label-free confocal Raman microscopy across different projects enables us to gain novel insights into the interactions of cells with their environment as well as with novel actives in a non-invasive and yet chemically-selective imaging approach.

Areas A-C - Cellular Homeostasis, Infection and Inflammation

Dr. Maria Vittoria Barbarossa

Frankfurt Institute for Advanced Studies

Ruth-Moufang-Straße 1

60438 Frankfurt am Main

barbarossa@fias.uni-frankfurt.de
Tel.: +49 69 798 47651
Barbarossa group

Our group works at the development of analytical and computational techniques for the description of processes arising in immunology and infectious diseases. In particular, we work on (i) in-host phenomena at intracellular level (e.g. signaling pathways), or at cellular level (e.g. interactions of immune cells with infected cells or tumor cells) (ii) between-hosts dynamics (e.g. pathogen transmission and social dynamics) and on the coupling of these two scales. This allows, for example, to capture the effects of individual immunity on epidemiological outbreaks in a population, or to study molecular mechanisms and events that influence the dynamic at cellular level (e.g. cell proliferation, death, functionality). Combining elements of nonlinear and infinite-dimensional dynamics with numerical simulations and optimization, we aim at both qualitative and quantitative understanding of biological phenomena.

Within ENABLE we will work across research areas with particular focus on (i) host-pathogen interactions, which largely determine the outcome of infections and impact on the susceptibility to numerous other diseases. We will employ hybrid modeling techniques to combine models of biochemical signaling events with the macroscopic dynamics of cellular interactions and (ii) inflammation, where we aim at investigating quantitative and dynamic analysis of HIF and other inflammation-mediating signaling pathways.

Prof. Dr. Rainer Haselmann

House of Finance
Goethe University Frankfurt
Theodor-W.-Adorno-Platz 3
60629 Frankfurt am Main

haselmann@econ.uni-frankfurt.de
Tel.: +49 69 798b 30031
Haselmann group

Potentially methodologies and insights from economic research can be applied to improve on the design of clinical trials as well as treatment choices. Rainer Haselmann adds a unique aspect from the financial perspective by monitoring costs of translational research and reducing the attrition rates during the development of novel medicines. Research in financial economics has developed several empirical methodologies to provide causal impact assessment of different institutional set-ups. While these methodologies are currently applied to evaluate different regulatory frameworks in financial markets, we will adapt and extend these approaches to evaluate clinical trial set-ups and different treatment choices. 

We will directly access relevant data to conduct empirical analysis. Statistical tests will be defined in close cooperation with medical scientists. These data will be used to study and evaluate incentives and/or information sharing across various actors in the supply chain of patient care. The overarching goal would be to improve patient therapy, to individualize therapy options, as well as to improve the design of clinical trials and to reduce attrition rates during the clinical development of novel medicines.
The DFG-funded Research Unit (FOR) 2774 on Foundations of Law and Finance (co-led by Haselmann) provides the needed framework and expertise from which this research will benefit.

Prof. Dr. Gerhard Hummer

Max Planck Institute of Biophysics

Max-von-Laue Straße 3

60438 Frankfurt am Main

gerhard.hummer@biophys.mpg.de
Tel.: +49 69 6303 2500
Hummer group

The Hummer group uses molecular dynamics simulations and modeling to study chemical probes in action, working hand-in-hand with the experimental teams. Artificial intelligence (AI) tools will be used to identify targets, to optimize probes and to propose intervention strategies. Critical input will come from molecular simulations of key events in selective autophagy of nuclear core complexes, ER-associated protein degradation (ERAD), and oocyte quality control. Overarching aims are to deepen the understanding of molecular events in cell homeostasis and infection and to turn this mechanistic understanding into quantitative and predictive models that lay the foundation for therapeutic strategies.

Prof. Dr. Ina Koch

Institute of Computer Science

Goethe University Frankfurt

Robert-Mayer-Straße 11-15

60325 Frankfurt am Main

ina.koch@bioinformatik.uni-frankfurt.de
+49 69 798 24651
Molecular Bioinformatics

Our group „Molecular Bioinformatics“ is developing and applying methods of network analysis and computational systems biology. We are applying semi-quantitative and quantitative modeling methods to explore biochemical systems. In this context, we also gain experience in data integration. We are applying graph theory and statistics to the analysis of protein-protein interaction networks for autophagy and ubiquitinated and phosphorylated proteins of Salmonella and Shigella.

We are interested in multi-scale modeling of biochemical systems based on diverse and incomplete data as it is often the case for signaling pathways. We apply Petri nets as a semi-quantitative formalism to analyze the dynamics of a system without knowing any kinetic parameter.  We use stochastics and kinetic modeling techniques if the available data is sufficient.

Within ENABLE, we will build up networks of protein-protein interactions in signaling pathways upon infections with Salmonella, Shigella, and A. baumannii to identify key genes/pathways/organelles. We will design mathematical models to simulate crucial processes, to generate new hypotheses and to analyze in silico perturbation experiments, thus supporting the design of experiments during the course of the project.

VACANCIES

The Cluster Project ENABLE - Unraveling mechanisms driving cellular homeostasis, inflammation and infection to enable new approaches in translational medicine is a newly established interdisciplinary research network which has been initiated jointly by the Goethe University Frankfurt, the Frankfurt Institute for Advanced Studies, the Fraunhofer Institute for Translational Medicine and Pharmacology, the Georg-Speyer-Haus and the Max Planck Institute of Biophysics. The network recently received funding from the State of Hesse and is looking to recruit:

8 postdoctoral scientists (m/f/d) (E13 TV-G-U, full time)

5 technology-oriented postdoctoral scientists (m/f/d) (E13 TV-G-U, full-time)

7 PhD students (m/f/d) (E13 TV-G-U, 65% part-time)

1 postdoctoral scientist in computational biophysics (m/f/d) (E13 TV-G-U, full time) 

1 postdoctoral scientist in biophysics (m/f/d) (E13 TV-G-U, full time)