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

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

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Maike Windbergs and Ivan Đikić


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

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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.

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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. 

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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.

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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.

Area B - Infection

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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.

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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.

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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.

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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

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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.

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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
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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.

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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.

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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.   

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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
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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.

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Prof. Jonel Trebicka, MD, PhD

Department of Internal Medicine I

Goethe University Frankfurt

Theodor-Stern-Kai 7

60590 Frankfurt

Jonel.Trebicka@kgu.de
Tel.: +49 69 6301 4256
Trebicka 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.

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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

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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.

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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.

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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.

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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)

project manager (m/f/d) (E13 TV-G-U, full-time)