17 PhD Positions at the Institute of Molecular Biology, Mainz, Germany


(1) PhD Position: The role of monocyte reprogramming in chronic venous thrombosis

In this project, we will study the effect of long-term chronic inflammation during clot growth and resolution on bone marrow myelopoiesis and monocyte profile. Therefore, we aim to systematically analyze the development of trained monocytes in thrombotic disease pathology and recurrence. Working steps consist in investigating the regulatory impact, phenotypic profiling, and functional evaluation of metabolic, epigenetic, and transcriptional alterations. The experiments will involve animal models as well as high-dimensional flow cytometry, immunohistochemistry, in vitro cell culture, chromatin immunoprecipitation assays, and unbiased molecular (single-cell) profiling approaches. This project is funded by the German Research Foundation (DFG).

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(2) PhD project: CurATime

This project is one of the lighthouse projects in “CurATime – Cluster for Atherothrombosis and Individualized Medicine” (www.curatime.org), a research cluster recently funded by the German Federal Ministry of Education and Research (BMBF) for €15 million for the first 3-year funding period. The goal of the PhD project is to help implement and to interpret the results of an analytical pipeline that prioritizes molecular signatures and specific targets for therapeutics, diagnostic and prognostic tools in the setting of atherothrombosis, by evaluating candidate targets along several relevant dimensions. This pipeline includes, among other things:

  • The identification and ranking of targets by innovative machine learning methods
  • Embedding targets in signaling pathways and studying their potential interaction with other pathways
  • Surveying candidate molecules’ on-target and off-target effects by assessing their relationship with different subclinical markers of atherosclerosis as well as organ damage markers and the broader clinical phenotype
  • Corroborating the validity of targets by external (cross-cohort) and orthogonal validation (e.g., by assessing the effect of SNPs or CpG site methylation in corresponding genes) 

Initiative and creativity are highly valued traits in the prospective candidate, and new ideas to further optimize the pipeline for its purpose are strongly encouraged. 

The human biodatabases used in this project are high-dimensional, spanning clinical and subclinical data (including detailed medical-technical information such as echocardiographic and coronary angiographic imaging), DNA (genotyping array with ~2.2M variants), proteomic and lipidomic data (targeted immuno-NGS-based multiplex assays, DIA mass spectrometry) as well as DNA methylation data (Illumina 850K MethylationEPIC array) and miRNA sequencing data (Next Generation Sequencing). In context of the larger curATime project, additional data will be generated and integrated as well, such as on autoantibodies and the microbiome. 

The candidate will be integrated in a friendly, professional and highly multidisciplinary team, comprising clinicians, epidemiologists, bioinformaticians, biostatisticians, as well as biologists and biochemists. Specific competences and supervisors are present to support the PhD candidate. Within the bioSignATure project, the candidate will additionally interact with experts in the fields of artificial intellligence (DFKI, German Research Center for Artificial Intelligence), bioinformatics with focus on interspecies ortholog mapping and pathway analysis (Computational Biology and Data Mining, Johannes Gutenberg University Mainz), drug/mRNA vaccine development (TRON gGmbH, Translational Oncology; BioNTech SE) as well as basic research in thrombosis (CTH, Center for Thrombosis and Hemostasis). The latter group will simultaneously perform multi-omics analyses in the context of mouse models, allowing bidirectional translation of results between species. 

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(3) PhD Project: Epigenetic adaptation and chromatin dynamics – bioinformatics

This position will perform computational analysis and integration steps of epigenomic methods, and will construct a prediction model of chromatin dynamics of adaptation and induced vulnerability. Bioinformatic expertise exists within our research group; the candidate will receive all relevant training to successfully complete these tasks.

If you are interested in this project, please select Sasca (bioinf) as your group preference in the IPP appcliation platform.

View details and apply

(4) PhD Project: Epigenetic adaption drives non-genetic resistance to therapeutic chromatin complex targeting in leukemia

Menin-MLL inhibitors currently assessed in clinical phase I trials have shown very promising clinical activity and caused remissions in many heavily pretreated (relapsed or refractory) AML patients. However – as observed with other targeted epigenetic drugs before – most of these remissions were transient, and secondary resistance development occurred in almost all of these patients. 
In preliminary work for this project, we have developed human and murine models of menin-inhibitor-resistant AML cells. Of note, sequencing of the menin-inhibitor-resistant AML cells demonstrated no mutations in the drug binding sites. RNA sequencing of these cells demonstrated specific leukemic gene expression programs to be reactivated compared to their non-resistant counterparts exposed to menin inhibition. These results are consistent with a non-genetic adaptation as a mechanism of resistance.
This project aims to shed light on the fundamental question of what processes drive resistance to menin-inhibitors and, more generally, how non-genetic resistance develops in cancer cells exposed to targeted epigenetic drugs. These questions will be addressed by characterizing the phenotypic changes associated with resistance in detail. We will start by integrating the already available transcriptomic data with an assessment of histone marks, global menin- and MLL chromatin binding, as well as an assessment of chromatin state using cut & run as well as single-cell next-generation sequencing techniques. Potential co-dependencies on the above-described interacting proteins will be assessed using CRISPR-Cas9 deletion in murine and human AML models as well as primary AML patient material.
This project is most suitable for a Ph.D. student who aims to ask fundamental biological questions about how chromatin-based mechanisms drive oncogenic processes and would like to work on a translational topic that directly affects how patients with leukemia are being treated.

View details and apply

(5) PhD project: The role of monocyte reprogramming in chronic venous thrombosis

In this project, we will study the effect of long-term chronic inflammation during clot growth and resolution on bone marrow myelopoiesis and monocyte profile. Therefore, we aim to systematically analyze the development of trained monocytes in thrombotic disease pathology and recurrence. Working steps consist in investigating the regulatory impact, phenotypic profiling, and functional evaluation of metabolic, epigenetic, and transcriptional alterations. The experiments will involve animal models as well as high-dimensional flow cytometry, immunohistochemistry, in vitro cell culture, chromatin immunoprecipitation assays, and unbiased molecular (single-cell) profiling approaches. This project is funded by the German Research Foundation (DFG).

View details and apply

(6) PhD project: “curAIvasc”

This project is part of “CurATime – Cluster for Atherothrombosis and Individualized Medicine” (www.curatime.org), a research cluster recently announced to be funded by the German Federal Ministry of Education and Research (BMBF) for €15 million for the first 3-year funding period. The goal of the curAIvasc-project is to develop innovative technologies and AI pipelines for the analysis of multi-dimensional biodata on vascular function and structure and to transfer them to patient-oriented research on atherothrombosis. As part of this project your tasks would be:

  • In close collaboration with DFKI you will be implementing and using a multidimensional/multimodal deep learning (DL) pipeline for image-based prediction of individual disease progression and personalized risk assessment.
  • Evaluating the created pipeline based on the harmonized analysis concept in the biodatabases. For this purpose, state-of-the-art methods of biostatistical analysis will be used, evaluating the quality and medical relevance of the newly developed pipeline.
  • Application of the established AI pipeline for biomedical interpretation, which includes the integration of the information from the DL pipeline into high dimensional multi-omics data (e.g. proteomics, genetics).

The candidate will be integrated in a friendly, professional and highly multidisciplinary team, comprising clinicians, epidemiologists, bioinformaticians, biostatisticians, as well as biologists and biochemists. Specific competences and supervisors are present to support the PhD candidate. Within the curAIvasc project, the candidate will additionally interact with experts in the fields of artificial intelligence (DFKI, German Research Center for Artificial Intelligence), experimental research (Center for Thrombosis and Hemostasis Mainz) and biotechnology (TRON/BioNTech).

View details and apply

(7) PhD Project: “CurAIheart”

This project is part of “CurATime – Cluster for Atherothrombosis and Individualized Medicine” (www.curatime.org), a research cluster recently funded by the German Federal Ministry of Education and Research (BMBF) for €15 million for the first 3-year funding period. The goal of the PhD project is to develop innovative technologies and pipelines for the analysis of biodata on cardiac function and structure and to integrate this novel pipeline in a systems medicine oriented approach for biomedical research on the development and progression of atherothrombosis. As part of this patient-oriented translational research project your tasks would include:

  • In close collaboration with Institute for Informatics (Prof. Stefan Kramer, Johannes Gutenberg University Mainz) you will be developing deep learning models for a novel echocardiographic pipeline
  • Facilitating the development of methods that can explain the predictions of a model at the individual and dataset level.
  • You will explore the complex interplay between cardiac structure and function across the span of early and late prevention of atherothrombosis by integrating multi-omics data for generation of an improved disease understanding.

The candidate will be integrated in a friendly, professional and highly multidisciplinary team, comprising clinicians, epidemiologists, bioinformaticians, biostatisticians, as well as biologists and biochemists. Specific competences and supervisors are present to support the PhD candidate. Within the curAIheart project, the candidate will additionally interact with experts in the fields of artificial intelligence (Institute for Informatics, University of Mainz and DFKI, German Research Center for Artificial Intelligence), experimental research (Center for Thrombosis and Hemostasis Mainz) and biotechnology (TRON/BioNTech).

View details and apply

(8) PhD project: CureATime

This project is one of the lighthouse projects in “CurATime – Cluster for Atherothrombosis and Individualized Medicine” (www.curatime.org), a research cluster recently funded by the German Federal Ministry of Education and Research (BMBF) for €15 million for the first 3-year funding period. The goal of the PhD project is to help implement and to interpret the results of an analytical pipeline that prioritizes molecular signatures and specific targets for therapeutics, diagnostic and prognostic tools in the setting of atherothrombosis, by evaluating candidate targets along several relevant dimensions. This pipeline includes, among other things:

  • The identification and ranking of targets by innovative machine learning methods
  • Embedding targets in signaling pathways and studying their potential interaction with other pathways
  • Surveying candidate molecules’ on-target and off-target effects by assessing their relationship with different subclinical markers of atherosclerosis as well as organ damage markers and the broader clinical phenotype
  • Corroborating the validity of targets by external (cross-cohort) and orthogonal validation (e.g., by assessing the effect of SNPs or CpG site methylation in corresponding genes) 

Initiative and creativity are highly valued traits in the prospective candidate, and new ideas to further optimize the pipeline for its purpose are strongly encouraged. 

The human biodatabases used in this project are high-dimensional, spanning clinical and subclinical data (including detailed medical-technical information such as echocardiographic and coronary angiographic imaging), DNA (genotyping array with ~2.2M variants), proteomic and lipidomic data (targeted immuno-NGS-based multiplex assays, DIA mass spectrometry) as well as DNA methylation data (Illumina 850K MethylationEPIC array) and miRNA sequencing data (Next Generation Sequencing). In context of the larger curATime project, additional data will be generated and integrated as well, such as on autoantibodies and the microbiome. 

The candidate will be integrated in a friendly, professional and highly multidisciplinary team, comprising clinicians, epidemiologists, bioinformaticians, biostatisticians, as well as biologists and biochemists. Specific competences and supervisors are present to support the PhD candidate. Within the bioSignATure project, the candidate will additionally interact with experts in the fields of artificial intellligence (DFKI, German Research Center for Artificial Intelligence), bioinformatics with focus on interspecies ortholog mapping and pathway analysis (Computational Biology and Data Mining, Johannes Gutenberg University Mainz), drug/mRNA vaccine development (TRON gGmbH, Translational Oncology; BioNTech SE) as well as basic research in thrombosis (CTH, Center for Thrombosis and Hemostasis). The latter group will simultaneously perform multi-omics analyses in the context of mouse models, allowing bidirectional translation of results between species. 

View details and apply

(9) PhD project: Host-microbiome interactions in cardiovascular disease

This project aims to investigate in more detail the interactions between the host, gut microbiome and medication in the context of atherosclerotic cardiovascular disease and atherothrombosis using a quantitative systems medicine approach. The project will take advantage of large prospective cohorts at UMC Mainz (Gutenberg Health Study (GHS), Prof. Dr P. Wild) which include comprehensive clinical phenotyping and biomaterial collection. Since the progression of cardiovascular disease has heterogeneous causes and manifestations, the project aims to obtain a deeper mechanistic understanding of the role of host-microbiome interactions during disease progression and divergent manifestations; the early prediction of disease development risk; and the stratification of patients for optimal care and drug allocation. The project will combine wetlab techniques for microbiome research with computational biology for omics and clinical data integration. We are looking for candidates interested in interdisciplinary research for which openness and flexibility are essential. Experience in omics data analysis is a plus.

View details and apply

(10) PhD project: Quality control of mislocalized proteins

In this project we will dissect the signals targeting proteins to mitochondria. We will take advantage of powerful yeast genetics and a new method for deep mutational scanning of localization signals developed in the group to define different mitochondrial targeting motifs and to understand the impact of disease mutations.
We are looking for a highly motivated individual with a degree in Molecular Biology, Biochemistry, Biotechnology or related fields. The successful candidate will join an enthusiastic team and combine genetic screening approaches with high-throughput fluorescence microscopy, deep sequencing techniques, biochemistry and molecular biology tools to uncover the features that are necessary to achieve protein localization to mitochondria. Excellent core facilities in the institute will provide the necessary support with fluorescence microscopy, sequencing and biochemistry requirements of the project.

View details and apply

(11) PhD project: “curAIvasc”

This project is part of “CurATime – Cluster for Atherothrombosis and Individualized Medicine” (www.curatime.org), a research cluster recently announced to be funded by the German Federal Ministry of Education and Research (BMBF) for €15 million for the first 3-year funding period. The goal of the curAIvasc-project is to develop innovative technologies and AI pipelines for the analysis of multi-dimensional biodata on vascular function and structure and to transfer them to patient-oriented research on atherothrombosis. As part of this project your tasks would be:

  • In close collaboration with DFKI you will be implementing and using a multidimensional/multimodal deep learning (DL) pipeline for image-based prediction of individual disease progression and personalized risk assessment.
  • Evaluating the created pipeline based on the harmonized analysis concept in the biodatabases. For this purpose, state-of-the-art methods of biostatistical analysis will be used, evaluating the quality and medical relevance of the newly developed pipeline.
  • Application of the established AI pipeline for biomedical interpretation, which includes the integration of the information from the DL pipeline into high dimensional multi-omics data (e.g. proteomics, genetics).

The candidate will be integrated in a friendly, professional and highly multidisciplinary team, comprising clinicians, epidemiologists, bioinformaticians, biostatisticians, as well as biologists and biochemists. Specific competences and supervisors are present to support the PhD candidate. Within the curAIvasc project, the candidate will additionally interact with experts in the fields of artificial intelligence (DFKI, German Research Center for Artificial Intelligence), experimental research (Center for Thrombosis and Hemostasis Mainz) and biotechnology (TRON/BioNTech).

View details and apply

(12) PhD Project: Targeting megakaryocytes to generate reparative platelets in atherothrombosis

The aim of this project is the development of a novel therapeutic approach that specifically addresses the thrombo-inflammation of atherothrombosis where multiple platelet functions are relevant: the local release of mediators stored in platelet granules and the stimulation/regulation of immune cells for wound healing and repair of the injured vessel wall. Together with our project partners, we aim to generate anti-inflammatory, reparative platelets by RNA-based targeting of platelet precursors (megakaryocytes). In the first project phase, our project partners will optimize nanodimensional lipid and polymer formulations for the specific targeting of megakaryocytes which will then be loaded with mRNA of selected targets. Using primary cell cultures of murine megakaryocytes and human iPSC-derived megakaryocytes, the candidate will investigate successful targeting of the megakaryocytes and transfer.

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(13) PhD Project: Epigenetic adaption drives non-genetic resistance to therapeutic chromatin complex targeting in leukemia

Menin-MLL inhibitors currently assessed in clinical phase I trials have shown very promising clinical activity and caused remissions in many heavily pretreated (relapsed or refractory) AML patients. However – as observed with other targeted epigenetic drugs before – most of these remissions were transient, and secondary resistance development occurred in almost all of these patients. 
In preliminary work for this project, we have developed human and murine models of menin-inhibitor-resistant AML cells. Of note, sequencing of the menin-inhibitor-resistant AML cells demonstrated no mutations in the drug binding sites. RNA sequencing of these cells demonstrated specific leukemic gene expression programs to be reactivated compared to their non-resistant counterparts exposed to menin inhibition. These results are consistent with a non-genetic adaptation as a mechanism of resistance.
This project aims to shed light on the fundamental question of what processes drive resistance to menin-inhibitors and, more generally, how non-genetic resistance develops in cancer cells exposed to targeted epigenetic drugs. These questions will be addressed by characterizing the phenotypic changes associated with resistance in detail. We will start by integrating the already available transcriptomic data with an assessment of histone marks, global menin- and MLL chromatin binding, as well as an assessment of chromatin state using cut & run as well as single-cell next-generation sequencing techniques. Potential co-dependencies on the above-described interacting proteins will be assessed using CRISPR-Cas9 deletion in murine and human AML models as well as primary AML patient material.
This project is most suitable for a Ph.D. student who aims to ask fundamental biological questions about how chromatin-based mechanisms drive oncogenic processes and would like to work on a translational topic that directly affects how patients with leukemia are being treated.

View details and apply

(14) PhD Project: Understanding the role of S-palmitoylation in DCs and other immune cells

S-palmitoylation is a metabolism-related protein post-translational modification (PTM) which dynamically modulates several aspects of protein biology. Owing to its unique reversible nature, palmitate attachment onto proteins primarily supports dynamic membrane targeting but also plays a pivotal role in protein stability, trafficking, and biological activity. Within the immune system, S-palmitoylation has been mainly studied in T cells where it is required for the assembling of immunological synapses and transduction of intracellular signals triggered by TCR engagement. In addition, several studies have elucidated the decisive role of S-palmitoylation in a broad array of host-pathogen interactions. However, no comprehensive studies concerning the implications of S-palmitoylation for dendritic cell (DC) function have been conducted so far. Therefore, the main goal of this research project is to unravel the role of S-palmitoylation in DC for immunity against pathogens and tumors. To this aim, we intend to use a range of methods from simple in vitro cultures to more complex in vivo experimental designs involving pathogens (bacterial and viral infection) or sterile inflammation (tumor) models. Hence, we will be able to have a global vision of DC reliance on S-palmitoylation for their interaction with other immune and non-immune cell types. Additionally, we will study the palmitoylome of primary DC upon activation. The composition of the palmitoylated proteome of putative palmitoyl acyltransferase (PAT) knock-out DC will also be dissected, thus allowing for the identification of druggable PAT-substrate pairs. Overall, this project aims to provide the first evidence of the impact of S-palmitoylation on DC activation and function and extend the results to other immune cells.

If you are interested in this project, please select Berod (S-palmitoylation) as your group preference in the IPP application platform.

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(15) PhD Project: Role of short-chain fatty acids and Ffar2 in DC metabolism and function

The interplay among dietary metabolites, the gut commensal microbiota, and the immune system is intimate and complex. Dietary intake of soluble fiber leads to their fermentation by commensal bacteria to short-chain fatty acids (SCFAs) in the gut. SCFAs have multiple effects on the colonic epithelium and are known to be an important energy source. Additionally, SCFAs can promote the differentiation of colonic Treg cells. However, how exactly SCFAs affect the function of other immune cells has yet to be elucidated. SCFAs can act as histone deacetylase inhibitors or bind and signal through G-protein-coupled receptors (GPCRs), such as the Free Fatty Acid Receptor 2 (Ffar2/Gpr43). Yet, due to the lack of appropriate models, the cell-type specific effects of Ffar2 have not been investigated. Thus, the aim of this project is to evaluate the specific contribution of SCFAs on the balance of tolerance versus immunity, particularly focusing on Dendritic cells (DCs). For this, we will use the novel Ffar2 conditional knockout mice to unveil the in vivo effect of SCFAs and discover new potential therapeutic targets.

If you are interested in this project, please select Berod (Ffar2) as your group preference in the IPP application platform.

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(16) PhD Project: The role of interferon-gamma signaling in NG2-glia during experimental autoimmune encephalomyelitis

Our laboratory has been studying extensively various aspects of MS pathogenesis, from the immune system activation at the periphery, to the events occurring at the CNS level [2-6].  In the frame of the present project, we will focus on the role of interferon-gamma (IFN-g), one of the key cytokines involved in MS pathogenesis, in modulating the fate and function of NG2-glia. Previous studies demonstrated that IFN-g blocks OPC differentiation and induces expression of molecules involved in antigen presentation. Here, we will apply various mouse models and cutting-edge techniques to investigate NG2 glia-specific IFN-g signaling in the context of experimentally induced neuroinflammation.

The presented project will provide a deeper understanding of the role of oligodendrocyte precursor cells (OPCs) in neuroinflammation. We aim to identify molecules, affected by IFN-g signaling, with possible roles in immune function and/ or progression to mature oligodendrocyte stages, which could then be subjected to pharmacological or genetic manipulation for a potential therapeutic intervention. In addition to identifying molecular mechanisms of IFN-g action in OPCs, the project will provide more conceptual insights into the function of these cells and their diversity in neuroinflammation.

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(17) PhD project: Host-microbiome interactions in cardiovascular disease

This project aims to investigate in more detail the interactions between the host, gut microbiome and medication in the context of atherosclerotic cardiovascular disease and atherothrombosis using a quantitative systems medicine approach. The project will take advantage of large prospective cohorts at UMC Mainz (Gutenberg Health Study (GHS), Prof. Dr P. Wild) which include comprehensive clinical phenotyping and biomaterial collection. Since the progression of cardiovascular disease has heterogeneous causes and manifestations, the project aims to obtain a deeper mechanistic understanding of the role of host-microbiome interactions during disease progression and divergent manifestations; the early prediction of disease development risk; and the stratification of patients for optimal care and drug allocation. The project will combine wetlab techniques for microbiome research with computational biology for omics and clinical data integration. We are looking for candidates interested in interdisciplinary research for which openness and flexibility are essential. Experience in omics data analysis is a plus.

View details and apply


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