PostDoc Job Opportunity
PI name & contact
details:
School:
Research Centre /
group affiliation:
Research group /
centre website:
First
Name
Last
Name
Marc
Devocelle mdevocelle@rcsi.ie
email
Institute
Address
RCSI
123, St. Stephen’s
Green, Dublin 2,
Ireland
Pharmaceutical and Medicinal Chemistry
http://pi.rcsi.ie/pi/mdevocelle/
Brief summary of research group / centre activity:
Established in 2000, the Peptide Laboratory at RCSI is associated with the Centre for Synthesis &
Chemical Biology (CSCB), has been involved in large Irish research programmes such the Science
Foundation Ireland Strategic Research Cluster, Irish Drug Delivery Network (IDDN), the National
Biophotonics & Imaging Platform Ireland and is involved in the BioAnalysis and Therapeutics
(BioAT) Programme. Since 2002, the laboratory has been involved in over 30 funded collaborations
in the area of peptide science with research groups across 9 Irish Higher Education Institutions (DCU,
ITT, NUIG, NUIM, RCSI, TCD, UCC, UCD, UL), 1 start-up and 1 multi-national companies.
Description of postdoctoral project on offer:
Nanomedicines against superbugs
Infections caused by antibiotic resistant bacteria have been listed as top priority diseases by the World
Health Organisation (WHO) in terms of their threat to global public health if the need for novel
medicines is not met. Resistant bacteria have been associated with serious hospital- and communityonset infections, worldwide. Bacterial pathogens exhibiting high-levels of multi-drug resistance,
including against therapeutic agents considered as last resort antibiotics such as carbapenems, are
emerging and pan-resistant strains have been reported. In addition to the limited number of therapeutic
options currently available, the problem is exacerbated by the lack of novel-mechanism antibacterials
in development that specifically target these resistant pathogens [1].
Host defence peptides (HDPs), also named cationic antimicrobial peptides, are multifunctional
molecular effectors of innate immunity, the first line of defence against infection in multicellular
organisms. They are recognised as promising candidates for the development of novel antimicrobial
agents, owing to their original mode of action which may circumvent the classical mechanisms of
antibiotic resistance [2]. However, while 1,200 to 1,700 HDPs are known or predicted, only
approximately 15 peptide-based therapeutic agents are currently in clinical trials and are generally
limited to topical anti-infective indications, reflecting the challenges associated with the development
of peptide-based systemic therapies. The main limitation currently preventing the clinical
development of HDPs is their unknown toxicity when administered systemically.
The host laboratory has developed an approach mimicking the natural control mechanism exerted on
HDPs, to confine the activity of these peptides to the sites of infection and/or target their delivery to
specific pathogens. In this approach, the peptides are produced as inactive precursors which can be
selectively converted into their active form by an enzyme confined to the site of infection [3]. While a
human enzyme was initially targeted for the activation of these peptide prodrugs, enzymes of bacterial
origin that have narrow substrate specificities and no mammalian homologues are now selected to
further investigate this approach. Opportunities exist to develop novel peptide-based antimicrobial
agents targeting a pathogen listed in the top 3 ‘hospital superbugs’ to which new antibiotics are
urgently needed. The inactive peptide precursors produced through this approach can be described as
nanomedicines, according the definition of the European Science Foundation.
[1] Boucher H, et al. Clin Infect Dis. 2009, 48:1–12.
[2] Zasloff M. Nature 2002, 415:389-95.
[3] Forde E, et al. Antimicrob Agents Chemother. 2014, 58(2), 978-985.
Please indicate the core skills or disciplines that are required for this position:
Organic synthesis
Please indicate the specific programme category under which the proposed postdoctoral project fits
Pharmaceuticals