PhD position (Computational Biology; Epigenetics & Nuclear Dynamics; Gene Regulation & Evolution): BioSignATure – Multi-Omics approach in Atherothrombosis (m/f/d)

Thinking of doing your PhD in the Life Sciences? The International PhD Programme (IPP) on Gene Regulation, Epigenetics & Genome Stability is offering talented students the chance to work at the cutting edge of research. As an IPP PhD student, you will join a community of exceptional scientists working on diverse topics ranging from how organisms age or how our DNA is repaired, to how epigenetics regulates cellular identity or neural memory.

Activities and responsibilities:

2 PhD positions in the curATime clusters4future initiative
Atherothrombotic disease (e.g., myocardial infarction, stroke) is the leading cause of death and disability worldwide, accounting for nearly one third of all deaths. The current generation of therapeutics (e.g., lipid lowering agents, antiplatelet agents, anticoagulants) insufficiently addresses the wide spectrum of pathomechanisms implicated in atherothrombosis. Hence, new and innovative drugs are needed. The largest efficiency bottleneck in traditional drug development is identifying the appropriate therapeutic target. Approximately 95% of drugs tested in human trials fail due to a lack of translatability of preclinical models to the human setting in a traditional drug development pipeline, resulting in a lack of efficacy or safety issues. Incorporating human data at an early stage could significantly reduce the preclinical target screening space. In the bioSignATure project, human multi-omics data from independent cohort studies will be used to discover new targets and assess their likely efficacy and safety. The primary discovery data level will be proteomics, specifically enabled through the use of the Olink Explore 3072 immuno-NGS assay, allowing the sensitive and specific relative quantification of nearly 3,000 proteins, and a DIA mass spectrometry approach to provide complementary coverage of the proteome. Different omics levels are used for orthogonal validation and more detailed assessment of target efficacy and safety. The availability of detailed clinical and subclinical information is instrumental in establishing evidence for target-disease linkage from several complementary angles.
PhD project: BioSignATure – Systems-oriented, multi-omics identification of biomarker signatures for atherothrombosis detection, quantification and treatment
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. Familiarity with systems biology/computational biology/bioinformatics approaches as well as knowledge of immunology and molecular mechanism of cardiovascular disease is desirable.

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.

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

What we offer:
• Exciting, interdisciplinary projects in a fully international environment, with English as our working language
• Advanced training in scientific techniques and professional skills
• Access to our state-of-the-art Core Facilities and their technical expertise
• Fully funded positions with financing until the completion of your thesis
• A lively community of more than 190 PhD students from 44 different countries

Requirements:
Are you an ambitious, young scientist looking to push the boundaries of science while interacting with colleagues from multiple disciplines and cultures? Then the IPP is your opportunity to give your scientific career a flying start!
All you need is:
• Master or equivalent
• Interactive personality & good command of English
• 2 letters of reference

For more details on the projects offered and how to apply via our online form, please visit https://www.imb.de/phd

The deadline for applications is 19 November 2022. Interviews will take place on-site in Mainz 16-18 January 2023.
Starting date: 1 March 2022 – 1 July 2023