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Peptide Antibiotics Developed by Mimicking Natural Antimicrobial Peptides
Turkey (TurkMSIC) - Acibadem University, Istanbul
Acibadem University School of Medicine Department of Medical Microbiology /Icerenkoy,Kayisdagi Street,No:32,34752,Atasehir/Istanbul
Prof. Dr. Tanil Kocagoz
Prof. Dr. Tanil Kocagoz
Type of Research Project
- Basic science
What is the background of the project?
Please, provide the background of the project (Provide information about the project; min. 10 lines, max. 25 lines) Antimicrobial peptides are widely preferred drugs for infectious disease treatment. Inspired from natural antimicrobial peptides, short peptides showing good antibacterial activity are designed in this study. The peptides consisted of repeating hydrophobic and positively charged amino acids, positioned on one side of the alpha helix. Arginine in peptides resulted in better activity compared to lysine. Having positively charged amino acids at both ends, created better activity for Escherichia coli compared to Staphylococcus aureus, and only at one end, created comparable activities for both organisms. Positioning of arginines on one side in zigzag form prominently increased the activity compared to positioning on linear axis. Elongating hydrophobic tail resulted in self-binding and eliminated the antibacterial activity. Molecular dynamic simulations suggested that a single molecule is capable of creating hydrophilic channel in membrane. Electron microscopic examination of staphylococci treated with these peptides revealed that the bacteria split into halves. Docking studies revealed that the peptides strongly bind to the major peptidoglycan synthesizing called glycosyltransferase. The unique composition and design of these peptides revealed a promising antibacterial activity that may further lead to the development of new antimicrobial compounds effective to multi-drug resistant organisms.
What is the aim of the project?
What is the aim of the project? (Highly specific: purpose?) The aim of the project is to design cathelicidin like helical peptides by mimicking natural antimicrobial peptides. Specific aims of the project include the production of these peptides, to make them resistant to proteases and study their activities in vitro and in vivo in animal models.
What techniques and methods are used?
What techniques and methods are used? Mention the steps/stages in this project. (Provide examples and avoid abbreviations; which tools will be used in general in this project?) Using bioinformatic programs for designing of peptides (These programs use for handling large volumes of data, to predict, analyse, or help interpret clinical and preclinical findings.) The minimum inhibitory concentration (MIC) (MIC, is the lowest concentration of an antimicrobial drug that will inhibit the visible growth of a microorganism after overnight incubation.) determination of the peptides. Haemolytic activity assays and cytotoxicity studies to determine the toxic effects of peptides on eukaryotic cells. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) studies and computational modelling to determine the mode of action of the antimicrobial peptides.
What is the role of the student?
- The student will mainly observe
- The tasks of the student will be performed on his/her own
What are the tasks expected to be accomplished by the student?
What are the tasks expected to be accomplished by the student? (Minimum 10 lines, provide detailed explanation) To fully understand the aim of the project, to learn and apply the techniques used in the project, especially to prepare bacteriological culture media, to grow bacteria used in the experiments, to prepare microtiter plates and make dilutions of the peptides to determine MIC, to grow HeLa (Henrietta Lacks-Patient’s name) cells (HeLa is an immortal cell line used in scientific research. It is the oldest and most commonly used human cell line. The line was derived from cervical cancer cells taken on February 8, 1951 a patient who died of cancer on October 4, 1951. for doing toxicity studies) to determine haemolytic activity for the peptides, to make preparations for electron microscopy studies for TEM and SEM, and to observe computational modelling
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Yes; there will be theoretical teaching about the background of the molecular techniques that are used in the project. The teaching will be about 3-4 hours every week by project director and researchers of the project.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a scientific report
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
What skills are required of the student? The student needs to have knowledge and experience regarding the following; - Laboratory hygiene and safety procedures - Essensials of clinical bacteriology and the mechanism of antimicrobial resistance development (such as bacterial efflux pumps or beta lactamases etc.) - Pharmacology of antibacterial medications - Phases of pharmaceutical development (ie. The 4 phases of a clinical trial)
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students
- For the use of students considering participating in the project; further information can be found from the following articles (Please add at least one specific article that is not a book; with correct reference) Peptide Antibiotics Developed by Mimicking Natural Antimicrobial Peptides Unubol N. et al.; Clin Microbiol 2017; 6:4 DOI: 10.4172/2327-5073.1000291
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