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Development of a new class of peptide antibiotics based on natural chicken host defence peptides

Friday 3 July 2009

Prof.dr Henk Haagsman and dr Edwin Veldhuizen

Cathelicidins are small host defence peptides (HDPs), part of the chicken innate immune system, with potent broad spectrum antimicrobial activity against pathogenic (including multidrug-resistant) bacteria and fungi as well as immunomodulatory properties. They are produced by heterophils, the avian counterpart of the neutrophil, stored in small granules and released and activated when in contact with bacteria. In contrast to many “classic” antibiotics, HDPs may use multiple mechanisms to kill microorganisms and the development of drug-resistance against HDPs appears to be low. Their microbicidal and immunomodulatory properties combined with minimal development of drugresistance makes them interesting candidates to serve as templates for development of a novel class of peptide antibiotics for prophylactic and/or therapeutical use. Previously, we have identified core elements linked to LPS neutralization and direct immune cell stimulation using human peripheral blood mononuclear cells (PBMCs) and ELISAs. We have developed several assays to monitor the effects of a 1th generation of chicken HDP-derived truncated and modified peptides (C-peptides) in chicken cell lines, isolated chicken cells and in vivo.

The project
The student will work on his/her own project within an enthusiastic group of people with similar research interests. The student will use the chicken macrophage-like cell line HD-11 and isolated chicken blood cell populations as model systems.

The project consists of 3 tasks:
1) Determine the LPS neutralizing effects of 1th and 2th generation peptides on cytokine production of HD-11 cells and chicken PBMCs, 2) determine the direct immunomodulatory effects of these peptides on HD-11 cells and PBMCs, 3) determine antibacterial activity against pathogenic (multidrug-resistant) bacteria

Techniques
The student will use the following techniques.
Cell culture: standard cell culture techniques, LPS/peptide-stimulation experiments
Microbiology: antimicrobial assays
Molecular biology: RNA isolation, Reverse transcription of RNA, PCR, quantitative PCR

Contact
Albert van Dijk, 030 - 2533379, A.vandijk1@uu.nl

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