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Postdoc: Computational Biology at the Interface of Gene Regulation and Protein Degradation Therapy

Employer: CeMM - Research Center for Molecular Medicine of the Austrian Academy of Sciences

Location: Vienna (AT)

Salary: We follow the recommendations of the FWF

Postdoc: Computational Biology at the Interface of Gene Regulation and Protein Degradation Therapy

We are recruiting an ambitious bioinformatics postdoc for a collaboration project that seeks to revolutionize cancer therapy by targeted, drug-induced degradation of important regulatory protein complexes. The project combines the expertise of two labs at the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences in Vienna, integrating large-scale data generation using cutting-edge technologies (chemical biology, epigenome sequencing, single-cell screening, mass spectrometry, imaging, etc.) with a deep interest in bioinformatics methods development and applications in systems medicine.

The Project

We pursue a systems-level understanding of gene regulation in leukemia, combining novel chemical biology, functional genetic screens, and cutting-edge sequencing technology. Using a powerful method for degrading any protein of choice in a matter of minutes (Winter et al. 2015 Science, Erb et al. 2017 Nature), we will induce specific perturbations of gene regulation in leukemia cells, and we will monitor the cellular responses using high-throughput assays such as PRO-seq, ATAC-seq, ChIPmentation, and single-cell transcriptome sequencing. Based on these data, the successful candidate will establish regulatory network models using causal modeling techniques, which will provide the basis for further functional validations and for the identification of potential drug targets. In summary, the project will combine computational and experimental methods to establish a model of cell state deregulation in leukemia and to provide a rationale for pharmacologic degradation in cancer therapy.

The Candidate

We are looking for highly motivated and academically outstanding candidates who want to pursue a scientific career in the fields of computational biology and/or functional (epi-)genomics. A strong candidate may have a background in the computational sciences (bioinformatics, statistics, physics, engineering, etc.) and some prior experience with collaborative research in high-throughput biology. In the same way, we are considering applicants with a background in medicine or in biology (e.g., functional genomics, chemical biology, human genetics, molecular medicine, etc.) who have strong quantitative skills and a keen interest in pursuing systems medicine projects. In this position you will work together with two laboratories and researchers of two different groups. This dual function requires excellent team player skills and a collaborative mindset as well as the ability to work independently.

Bock Lab

The Medical Epigenomics Lab at CeMM pursues an interdisciplinary and highly collaborative research program aimed at understanding the cancer epigenome and establishing its utility for precision medicine. Led by Christoph Bock – a computational biologist, ERC grantee, and recipient of the Overton Prize of the International Society of Computational Biology (2017) – the lab pursues several lines of research:

Epigenomics. Many diseases show widespread deregulation of epigenetic cell states. As members of the International Human Epigenome Consortium, we use epigenome sequencing to dissect the epigenetic basis of cancer and immune disorders.

Technology. Groundbreaking biomedical research is often driven by new technologies. Our lab is therefore heavily invested into technology development, including single-cell sequencing, CRISPR screens, and epigenome editing.

Bioinformatics. New algorithms and advanced computational methods allow us to infer epigenetic cell states from large datasets, in order to reconstruct the epigenetic landscape of cellular differentiation and complex diseases.

Diagnostics. New technologies (genome sequencing, mobile devices, etc.) provide important information for personalized medicine. We develop and validate assays and algorithms for translating the value of digital medicine into routine clinical practice.

Winter Lab

The mission of our new lab at CeMM (started 2016) is to devise pharmacologic strategies to understand oncogenic gene regulation and to innovate novel therapeutic approaches to modulate transcriptional dysregulation in cancer. In particular, we are developing targeted protein degradation as a new paradigm to therapeutically disrupt, probe, and understand molecular machines involved in oncogenic transcription (Winter et al. 2015 Science, Erb et al. 2017 Nature). Targeted protein degradation allows elimination of proteins within minutes after ligand exposure, hence enabling us to derive mechanistic insights at an unprecedented kinetic resolution. We are combining such acute perturbations with genome-scale technologies that report on gene activity, genome structure and chromatin function in a quantitative fashion. We expect that our strategy uncovers a new level of a functional understanding of oncogenic transcription. Integrative analysis will enable us to model disease-relevant transcriptional circuits and gene-regulatory networks. This will rationalize novel therapeutic targets that are based on an unprecedented understanding of the transcriptional wiring of cancer cells.

The Institute

CeMM is an international research institute of the Austrian Academy of Sciences and a founding member of EU-LIFE. It has an outstanding track record of top-notch science (last five years: >10 papers in Nature/Cell/Science/NEJM, >25 papers in Nature/Cell sister journals) and medical translation. With just over a hundred researchers, CeMM provides a truly collaborative and personal environment, while maintaining critical mass and all relevant technologies. Research at CeMM focuses on cancer, inflammation, and immune disorders. CeMM is located at the center of one of the largest medical campuses in Europe, within walking distance of Vienna’s historical city center. A study by “The Scientist” placed CeMM among the top-5 best places to work in academia world-wide. Vienna is frequently ranked the world’s best city to live. It is a United Nations city with a large English-speaking community. The official language at CeMM is English, and more than 40 different nationalities are represented at the institute. We are convinced that diversity and a multicultural work environment are clear advantages for successful research and are committed to attract, develop, and advance the most talented individuals regardless of their gender, race, sexual orientation, religion, age, disability status or any other dimension of diversity.

Please apply online with cover letter, CV, academic transcripts, and contact details of three referees. Applications will be reviewed on a rolling basis. Any application received by 15 August 2017 will be considered. Start dates are flexible.

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