PhD position on antimicrobial peptides

A three-year PhD position is available at the GEC Department, University "Picardie Jules Verne" (UPJV) in Amiens, France, to study the interaction of antimicrobial peptides with biomimetic membranes.

 

Scientific background

Antimicrobial peptides (AMPs) form a very large family of natural peptides with an astonishing variety of activities (antibacterial, anti-fungal, antiviral and anti-tumor) with an impact in medicine (as drugs targeting cancer or antibiotic-resistant super-bugs) and agriculture (as an alternative to pesticides). They are produced in all living kingdoms, from bacteria to humans, including plants, insects and animals, playing a key role in immunity. With the threat of multi-drug resistant bacteria, already appearing in mainstream information, there is no wonder that great interest has been directed towards these simple molecules. In agriculture, the use of optimized AMPs might address the emergency of the environmental damage caused by the use of pesticides. With the advent of genome editing (e.g. the recent CRISPR-Cas9 technique), plants can be engineered to produce antimicrobial peptides and become resistant to microbial, fungal or even insect attacks.

 

The rationale of the project

​The activity of AMPs is often exerted by targeting the pathogen’s cell membrane, making bacteria less prone to develop mutation-driven resistance compared to classical antibiotics. In addition, they tend to be selective towards the target organism. ​Studying the interaction of AMPs with biological membranes is of paramount importance for the understanding of their mechanism of action, their selectivity, and consequently, the development of new active peptides to be used in medicine and agriculture.

 

Methodology​ ​

In this project, various peptides with activity towards cancer, bacteria and fungi will be studied. Other peptides, rationally designed with the aid of bioinformatics, will be tested towards various microbes. AMPs displaying interesting properties will be studied in their interaction with synthetic membranes, mimicking those of erythrocytes, cancer cells, plants or fungi. Multiple techniques will be used (microscopy, circular dichroism, SEC-MALS) with special emphasis on both liquid and solid state NMR. Paramagnetic probes will be used to locate the peptide in the ​​membrane and to determine its structure and dynamics.​ ​Molecular modeling driven by experimental data will aid the structure determination. ​The FATSLIM software (Fast Analysis Toolbox for Simulations of Lipid Membranes), developed at GEC, will be used for detailed in silico analysis of the interaction with bio-mimetic membranes.​

 

The GEC laboratory​ ​at UPJV

The GEC Department (Enzymatic and Molecular Engineering) at UPJV is dedicated to the study of the cell biochemistry in animals and plants. NMR is a key technique in the research on the metabolism, structure and dynamics of​ ​bio-molecules.​ ​The​ ​department​ ​has long experience in the preparation and the modeling of biological membranes, an important part in the development of the project.​ UPJV provides access to the​ ​molecular biology, electron​ ​microscopy, ​​greenhouse​ ​and analytical platforms. In the latter, MS (LC/MS,​ ​GC/MS​ ​and MS/MS)​ ​and NMR (400, 500 and 600 MHz with auto-sampler) instruments are available.​ ​The UPJV, in conjunction with UTC (Université Technique de Compiègne), has​ ​also access to​ ​an S2 containment greenhouse, a​ ​laboratory for the manipulation of L2 biological agents, and a​ ​cell culture laboratory.

 

The doctoral school

The UPJV Doctoral School of Sciences, Technology and Health, created in 2000, has been accredited by the Ministry of Research and Higher Education. It brings together the 22 recognized research units in the sciences and health sectors​ ​that provide scientific supervision for the​ ​more than 200​ ​PhD students currently enrolled.​ ​I​t is multidisciplinary, spanning from cancer research, aging and neuroscience to energy storage, agro-science and green chemistry.

 

Amiens and its surroundings

Amiens is the main town of Picardie (now part of Hauts-de-France department), a region situated just north of Paris.​ Its cathedral is visited by 800000 people each year and it is the tallest gothic church and the largest cathedral in France​ ​(UNESCO world heritage). The town is crossed by numerous canals, making it one of the "Venice of the north". Floating gardens (hortillonnages​)​ ​are set ​over a course of 65 km of irrigation canals​. ​Amiens also hosts one of the largest university hospitals in France. The University brings into town about 28000 students, animating its atmosphere. Its location, close to the north coast, Lille and Paris (Paris can be easily reached by train in about 1 hour), makes it a quiet and interesting place to live.

 

Eligibility

The successful candidate should have obtained a Master (or equivalent title) in the field of chemistry, biology, physics or related disciplines, be eager to learn and able to work both independently and in group. Theoretical knowledge of biochemistry, basic practical experience in laboratory and an intermediate level of English are mandatory. Experience in bioinformatics or computer programming is not required, but will be considered a plus. Other advantageous expertise includes: experience in production and purification of proteins and / or experience in solid-state or solution NMR.

 

How to apply

Interested candidate should send applications to​ ​nicola.damelio@u-picardie.fr​.

- A full curriculum vitae detailing the university modules (the transcript of the courses from the first year of University to the last year of the Master and their marks), the classification obtained each year and the number of credits.

- A letter of recommendation from the head of the host team and/or the supervisor in which the student has completed his master training period.

- The names of two referees.

- A letter of motivation from the candidate clearly highlighting the competencies he/she thinks he/she has acquired to carry out the project.

 

Selected candidates will be called for an interview (in English or French, based on their preferences).

 

Useful information/dates

Deadline for application: 31/05/17

Starting in October 2017

The scholarship of about 1400 € net/month fully covers the three years.

 

For further information on the project, contact:

Nicola D'Amelio: email ​​nicola.damelio@u-picardie.fr

 

For further information on the doctoral school, contact:

ed-sciences-sante@u-picardie.fr

 

 

REFERENCES

1.            Field, D., Des, F., Cotter, P. D., Colin, H. & Ross, R. P. Bioengineering Lantibiotics for Therapeutic Success. Front. Microbiol. 6, (2015).

2.            Mulder, K. C. L., Lima, L. A., Miranda, V. J., Dias, S. C. & Franco, O. L. Current scenario of peptide-based drugs: the key roles of cationic antitumor and antiviral peptides. Front. Microbiol. 4, 321 (2013).

3.            Breen, S., Solomon, P. S., Bedon, F. & Vincent, D. Surveying the potential of secreted antimicrobial peptides to enhance plant disease resistance. Front. Plant Sci. 6, 900 (2015).

4.            Mäler, L. & Lena, M. Solution NMR studies of cell-penetrating peptides in model membrane systems. Adv. Drug Deliv. Rev. 65, 1002–1011 (2013).

5.            Fan, L. et al. DRAMP: a comprehensive data repository of antimicrobial peptides. Sci. Rep. 6, 24482 (2016).

6.            Kouzayha, A., Wattraint, O. & Sarazin, C. Interactions of two transmembrane peptides in supported lipid bilayers studied by a (31)P and (15)N MAOSS NMR strategy. Biochimie 91, 774–778 (2009).

7.            Wattraint, O., Saadallah, I., Silva-Pires, V., Sonnet, P. & Sarazin, C. Influence of the insertion of a cationic peptide on the size and shape of nanoliposomes: a light scattering investigation. Int. J. Pharm. 454, 621–624 (2013).

8.            Buchoux, S. & Sébastien, B. FATSLiM: a fast and robust software to analyze MD simulations of membranes. Bioinformatics (2016).