SFB 1279:  Exploiting the Human Peptidome for Novel Antimicrobial and Anticancer Agents

• Subject Area: Medicine ; Biology ; Chemistry ; Materials Science and Engineering ; Physics
• Term: since 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 316249678

The goal of CRC 1279 is to discover endogenous human peptides that play key roles in the control of human pathogens and cancers and to optimize them for potential therapeutic applications. To achieve this, the CRC exploits the peptidome, i.e. the entirety of peptides in the human body. This source is of enormous interest because peptides govern numerous physiological and pathological processes. In addition, peptides are key regulators and effectors of innate and adaptive immunity and modulate the survival, growth and metastatic spread of cancer cells. Despite its importance, the human peptidome is functional hardly explored. The main reason for this is its enormous complexity, which makes purification of individual bioactive peptides challenging. In this CRC, we are utilizing comprehensive peptide libraries from human body fluids and tissues for the stepwise purification of endogenous bioactive compounds detected in specific fractions by repeated rounds of functional assays and separation. This approach allows the isolation of bioactive peptides from mixtures of up to millions of naturally-occurring compounds. It has proven highly successful and allowed the discovery of numerous as-yet-unknown endogenous agents displaying antimicrobial (i.e. antiviral or antibacterial) and/or anticancer (i.e. antineoplastic or antimetastatic) activity. The framework of expertise and resources available in the CRC allows to define their mode of action and physiological relevance, and to apply state of the art technologies to optimize natural peptides for translational in vivo applications. Notably, a significant portion of endogenous peptides exerts both antimicrobial and antineoplastic activity and could be optimized for therapeutic development. The CRC is highly interdisciplinary and organized in three synergistic research areas supported by two essential technology platforms. The first core project generates and provides peptide libraries to the research projects and support them in peptide purification, synthesis, structural analysis and molecular modelling. Projects in area A characterized and optimized numerous antimicrobial peptides. Projects in area B discovered and analyzed the role of endogenous peptides in cancer growth and metastasis, focusing in particular on leukemic and cancer stem cells. In close cooperation with areas A and B, projects in area C develop novel tools and methodologies to optimize the activity, stability and delivery of the bioactive peptides. The CRC is complemented by a technology platform allowing to test the distribution, tolerability and bioavailability of peptides in animal models. The research consortium opens a new, highly challenging field of research to obtain new insights into the role of endogenous peptides in infectious and oncological processes. It will clarify whether the generation of antimicrobial and antineoplastic peptides from abundant precursors by immune-activated proteases represents a common principle in innat

• DFG Programme: Collaborative Research Centres

Current projects

• A01 - Identification and functional optimization of antimicrobial peptides with activity against Mycobacterium tuberculosis (Project Heads Michaelis, Jens ;  Stenger, Steffen )
• A02 - Identification and characterization of antimicrobial peptides from major pathogen entry and replication sites (Project Heads Münch, Jan ;  Spellerberg, Barbara )
• A03 - Amyloid biology of bioinspired peptides - from basic research to preclinical development (Project Heads Fändrich, Marcus ;  Münch, Jan ;  Walther, Paul )
• A04 - Characterization of novel peptide ligands of GPCRs involved in lentiviral infections (Project Head Kirchhoff, Frank )
• A05 - Peptides targeting the fusion peptides of enveloped viral pathogens (Project Heads Kirchhoff, Frank ;  Weil, Tanja )
• A06 - Characterization and optimization of the CXCR4 antagonist EPI-X4 (Project Heads Klein, Florian ;  Münch, Jan ;  Sanchez Garcia, Elsa )
• A07 - Endogenous peptides as novel inhibitors of the Bordetella pertussis toxin (Project Heads Barth, Holger ;  Ernst, Katharina )
• A08 - Regulation of autophagy by human peptides and exploration of their anti-microbial and anti-cancer properties (Project Head Sparrer, Konstantin )
• B01 - Characterization of endogenous peptides targeting leukemic stem cells in acute myeloid leukemia (Project Head Buske, Christian )
• B03 - Identification of endogenous peptides for the treatment of transformed B cells (Project Heads Jumaa, Hassan ;  Übelhart, Rudolf )
• B05 - Identification and mechanism of human peptides protecting against therapy-induced leukemia (Project Heads Gebhardt, Christof ;  Wiesmüller, Elisabeth Maria )
• C01 - Synthesis of peptide and protein biohybrids with improved features (Project Heads Barth, Holger ;  Otto, Markus ;  Weil, Tanja )
• C02 - Biohybrid transporters for cell type-specific delivery and controlled release of pharmacologically active peptides (Project Heads Barth, Holger ;  Michaelis, Jens )
• C03 - Mesoporöse Silica-Nanopartikel zur kontrollierten Freisetzung von Peptid-Wirkstoffen (Project Head Lindén, Mika )
• C04 - Fluorescent nanodiamonds as biocompatible markers and sensors for simultaneous peptide delivery and bioimaging (Project Heads Jelezko, Fedor ;  Weil, Tanja ;  Wu, Ph.D., Yuzhou )
• Z01 - Peptide libraries, purification, synthesis and structural analyses (Project Heads Jacob, Timo ;  Kaiser, Ute ;  Read, Clarissa ;  Ständker, Ludger ;  Wagner, Manfred ;  Wiese, Sebastian )
• Z02 - Peptide evaluation and molecular imaging in vivo (Project Heads Beer, Ambros ;  Rasche, Volker ;  Weidinger, Gilbert )
• Z03 - Central tasks of the CRC (Project Head Kirchhoff, Frank )

Completed projects

• B02 - Bioactive peptides in normal and compromised hematopoiesis (Project Head Geiger, Hartmut )
• B04 - Targeting CXCR4 signaling to eliminate metastatic cancer stem cells in pancreatic cancer (Project Head Hermann, Patrick C. )
• C06 - Hyperpolarized peptide-coated nanodiamonds for magnetic resonance imaging (Project Heads Buske, Christian ;  Jelezko, Fedor ;  Plenio, Martin Bodo )

• Applicant Institution: Universität Ulm
• Business and Industry: Universität zu Köln
• Participating University: Universität Duisburg-Essen
• Participating Institution: Max-Planck-Institut für Polymerforschung
• Spokesperson: Professor Dr. Frank Kirchhoff