PhD positions: Elucidation of the mechanisms of action of immune‐activating HDAC inhibitors and natural products for the development of new therapeutic approaches against chemoresistant tumor cells and bacterial pathogens Heinrich-Heine-Universität • Pharmazeutische und Medizinische Chemie / Mathematik-Naturwissenschaften • Düsseldorf

Germany Universities

Germany

June 30, 2022

Description

Open Positions 1

Time Span 01 Oct 2022 for 3 years Application Deadline 30 Jun 2022 Financing yes Type of Position

  • PhD - Doctoral Programme
  • Field of Research

  • Mathematics / Natural Sciences
  • Subjects Immunology Description Applications are invited for a PhD student position available 01.10.2022 in the Institute of Medicinal Microbiology & Hospital Hygiene (Prof. Dr. Stefanie Scheu; https: // www. medmikrobio.hhu.de/) at the University Hospital, Düsseldorf, Germany.

    Abstract:

    The development of resistances against cytostatic drugs or antibiotics is currently a major challenge in the treatment of cancer and infectious diseases. Combining a direct tumoricidal or bactericidal activity with an immunomodulatory effect within one and the same substance may synergistically counteract the development of resistance. Using a specifically designed screening pipeline to identify new lead structures, a library of natural product isolates and natural product-derived histone deacetylase inhibitors (HDACis) has been screened for a capacity to activate intrinsic effector functions of primary murine antigen-presenting cells and compared with screening results from other GRK projects with respect to direct antitumor and antipathogenic properties. Several polypharmacological compounds have been identified that are able to activate or potentiate type I interferon and IL-12 production as well the antigen-presenting capacity of dendritic cells while having a direct toxic effect on tumor cells. The goal of this project is to characterize the molecular mechanisms underlying the immunomodulatory capabilities of the respective compounds. From the identified immune- activating natural products or HDACis, exact lead structures will be derived and functionally modified after successful target discovery in close collaboration with other labs of the Research Training Group.

    Requirements: The ideal candidate will have a record of excellence and a strong background in immunology/cellular biology or molecular biology and biochemistry.

    Recommended literature:

    Yang, X. et al. The mycotoxin Beauvericin exhibits immunostimulatory effects on dendritic cells via activating the TLR4 signaling pathway. Front Immunol, accepted for publication, bioRxiv: 2022.2001.2020.476919 (2022).

    Salmon, J. et al. Epigenetic activation of plasmacytoid DC drives IFNAR- dependent therapeutic differentiation of AML. Cancer Discov doi: 10.1158/2159-8290.CD-20-1145. Epub ahead of print (2022).

    Richter, L., Kropp, S., Proksch, P. & Scheu, S. A mouse model-based screening platform for the identification of immune activating compounds such as natural products for novel cancer immunotherapies. Bioorg Med Chem 27, 115145 (2019).

    Bauer, J. et al. Cutting Edge: IFN-beta Expression in the Spleen Is Restricted to a Subpopulation of Plasmacytoid Dendritic Cells Exhibiting a Specific Immune Modulatory Transcriptome Signature. J Immunol 196, 4447-4451 (2016).

    How to apply: Applicants should submit application documents as listed here https: // www. grk2158.hhu.de/positions-for-doctoral-students by email to grad2158atuni-duesseldorf.de, specifying the position 119.22 – 3.1 in the email subject.

    Detailed information about living and studying in Düsseldorf is provided here: https:// www. uni-duesseldorf.de/home/leben-in-duesseldorf.html

    Working Language

  • English
  • Language of Dissertation

  • English
  • German
  • Required Documents

  • CV
  • Transcripts
  • Letter of Motivation
  • Others : Application form: https: // www. grk2158.hhu.de/positions-for- doctoral-students
  • More Information https: // www. grk2158.hhu.de/positions-for-doctoral- students

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