Collaborative Research Centre 1279

Exploiting the Human Peptidome for Novel Antimicrobial and Anticancer Agents

The human peptidome (i.e. the entirety of peptides in the human body) comprises millions of diverse agents orchestrating numerous important physiological and pathological processes. Among other things, peptides are key regulators and effectors of innate and adaptive immunity and affect the survival, growth and metastatic spread of cancer cells. To date, only a very small fraction of endogenous peptides has been functionally characterized because the enormous complexity of the peptidome makes purification of individual bioactive agents highly challenging. Thus, the peptidome represents a hardly explored and almost unlimited resource for the discovery of novel effector molecules. The main goal of the proposed CRC is thus to use the human peptidome to discover endogenous peptides playing key roles in the control of human pathogens and cancers, and to apply state of the art technologies to optimize them for translational in vivo applications. In proof-of-principle experiments, members of the proposed CRC have already shown that peptide libraries generated from body fluids allow the discovery of novel bioactive agents playing important and often unexpected roles in infectious diseases and cancers.
The proposed CRC aims at optimizing available endogenous effector molecules and will use peptide libraries from various body fluids and tissues for the discovery of as-yet-unknown endogenous agents displaying antimicrobial (i.e. antiviral and antibacterial) and/or anticancer (e.g. anti-neoplastic and anti-metastatic) activity. The initiative will focus on infectious diseases and cancer because they are highly relevant for human health and since endogenous peptides often exert both antimicrobial and anticancer activity offering promising prospects for therapeutic development. To achieve its ambitious goals, the proposed CRC will be organized in three cooperative research areas. Projects in area A will focus on the discovery, characterization and optimization of antimicrobial peptides. Research area B aims at understanding the biological role of endogenous peptides in cancer growth, focusing in particular on leukemic and cancer stem cells and the crosstalk between cancer cells and their microenvironment. Major goals of projects in area C are the application of novel tools and methodologies to optimize the activity, stability and delivery of the bioactive peptides analyzed in areas A and B. Moreover, novel physics technologies will be developed to image peptides, their targets and mechanism(s) of action with hitherto unachieved resolution and sensitivity. The research projects will be supported by two technology platforms providing (I) access to peptide libraries and support for peptide purification, synthesis, structural characterization and molecular modelling and (II) the possibility for testing the distribution, tolerability and bioavailability of peptides in animal models. The CRC will open a new, highly challenging field of research to obtain fundamentally new insights into the role of endogenous peptides in infectious and oncological processes and to translate these findings into the development of novel peptide-based imaging tools and therapeutics.

Speaker

Kirchhoff, Frank, Prof. Dr. Dr.

Institute of Molecular Virology
Ulm University Medical Center
Meyerhofstr. 1
89081 Ulm
Tel: 0731 50065150
frank.kirchhoff(at)uni-ulm.de

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