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Project List » Molecular characterization of antimicrobial peptides action mechanisms and de-novo prediction of molecular structures with enhanced antimicrobial potential

Molecular characterization of antimicrobial peptides action mechanisms and de-novo prediction of molecular structures with enhanced antimicrobial potential
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Acronym: ANTIMPEP
Contracting Authority: Executive Agency for Higher Education, Research, Development and Innovation Funding (UEFISCDI)
Number / Date of the contract: 61-016 / 18.09.2007
Parteneriate in domeniile prioritare
Project Manager: Mihai Radu
Partners: University of Bucharest; University Al. I. Cuza, Iassy
Starting date / finishing date: 2007-09-18 / 2007-09-17
Project value: 2000000 RON
Abstract: One of the major focuses in today’s research in life sciences, and health sciences in particular, is being represented by the urge of finding novel paradigms able to boost cell defence against various pathogens. One extremely promising way to meet this demand is based on the concept of antimicrobial peptides (AMPs). AMPs belong to a specific class of relatively small peptides (10 kDa) which are found throughout the vegetal and animal biosystems, and were proven to effectively target and annihilate a number of microbes and viruses. However, molecular mechanisms of AMPs interacting with biomembranes are less known, and only for a limited number of such peptides; in a nutshell, it is widely acknowledged that the cyto-toxic activity of AMPs stems from the aqueous pore formation within target membranes through which water and small molecules and ions can diffuse down their electrochemical gradients, leading eventually to the complete lysis of the targeted cell. In this project we aim at employing a multi-disciplinary approach to understand the mechanisms via which AMPs perform their lytic function, and the main objectives followed will be: (1) selection of those types of AMPs which display maximal lytic activity and yet least secondary effects (2) in-depth analysis and comprehension of chemical, biological and physical factors which govern the lytic capability of selected AMPs and ways they correlate to AMPs efficacy and (3) de novo prediction of new molecular structures of possibly more specific and efficient AMPs. As such, the envision activities will be undertaken on several parralel and complementary pathways: (a) the close study of AMPs lytic properties of selected AMPs on mamalian and microbian cells via electrophysiology and molecular biology related techniques, with the goal of closing in to the most efficient and less toxic AMPs (b) study of the interaction between AMPs and reconstituted and natural membranes, with the definite goal of determining those parameters which rule such interactions (c)molecular modeling of novel and improved AMPs, based on the selected, natural ones. This project will be implemented by three groups with acknowledged reputation on this field: IFIN-HH, University of Bucuresti and ‘Al. I. Cuza’ University of Iasi. The main techniques to be used are based upon top-notch protocols from cellular and molecular biology, electophysiology at the single-molecule level, fluorescence spectroscopy and molecular modeling

Objectives:

THE STAGES OF THE PROJECT AND DELIVERY DATES
1. To optimize the experimental methods for evaluating the antimicrobial capacity of AMPs and their side effects on eukaryotic cells  (2007-12-15)
2. The AMPs effects on cells and model membranes: cytotoxiciy and electrophysiology studies (2008-06-15)
3. Effects of AMPs on cells and model membranes: microbiology and ionic transport across the membrane (first section) (2009-01-01)
4. microbiology and ionic transport across the membrane (second section) (2009-12-15)
5. AMPs effects on mammalian cells; analgesic effects of AMPs on in vitro cell cultures (2010-06-30)
6. Optimization of AMPs effect and prediction of new AMPs structures with increased pharmacological potency (2010-09-17)
RESULTS
PUBLISHED ARTICLES
RESEARCH TEAM


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