Embedded Files
ASSISTANT PROFESSOR POSITION IN BIOCHEMISTRY (permanent, from September 2025) - NOW CLOSED
An assistant professor position (Maitre de conferences) in biochemistry is offered in Amiens at the University of Picardie Jules Verne (UPJV) in the lab “Enzyme and Cell Engineering, Molecular Recognition and Biocatalysis UMR 7025 CNRS.
Contact : nicola.damelio@u-picardie.fr and catherine.sarazin@u-picardie.fr
Job profile
Research: The candidate will demonstrate a solid expertise in biophysics applied to the structural study of biomolecules in relation to their interactions, either within reaction systems or with biological targets. He/she must demonstrate strong knowledge of one or more spectroscopic techniques such as nuclear magnetic resonance (NMR) liquid and/or solid or circular dichroism (CD). Experience in light scattering techniques (SEC-MALS, DLS) and/or electron microscopy (SEM, TEM) would also be a major asset. Depending on their skills and interests, the candidate will be free to integrate into one of the two research themes developed in the laboratory.
(i) Valorization of the whole plant
These research activities consist in developing innovative and sustainable strategies for the fractionation of lignocellulosic biomass and its enzymatic (hydrolases, oxidoreductases) and/or microbiological transformation. This research opens up the way to various applications such as the production of bioproducts, biomaterials and biofuels. In addition to these applied aspects, the biophysical approach will contribute to advancing the molecular understanding of the strategies implemented.
(ii) Biomimicry and molecular interactions
These activities aim to understand the mechanisms underlying the interactions between natural compounds and their biological targets or biomimetic systems, including cell membranes. The objective is to develop new active molecules for various applications in the medical field (antibiotics, antifungals and anticancer agents), or agricultural (molecules stimulating defense mechanisms in plants).
Peptides and their derivatives are privileged research axes.
A positioning at the interface of these two themes will be encouraged in the medium or long term, thus allowing the future assistant professor to build a multidisciplinary research profile. The application must include a research project describing the integration into the laboratory.
Teaching in biochemistry: The teaching of the biochemistry/microbiology SVT department (Science de la Vie et de la Terre) covers, at the undergraduate level (from L1 to L3), general and structural biochemistry, biological macromolecules, biochemical analysis techniques, and enzymology. Complementary teaching for the Master of Chemistry (speciality biotechnologies of natural resources) is also to be considered: extraction and purification of biological molecules and structural biology. Teaching will be in French, especially at undergraduate level.
Responsibility for teaching units and involvement in innovative pedagogical projects are expected.
Salary
Indications on the salary can be found here.
GEC laboratory in Amiens
The Unit of Enzyme and Cell Engineering, Molecular Recognition and biocatalysis (GEC), has acquired national and international recognition in the field of biotechnology. The GEC develops approaches combining the optimization of bioresource use and plant metabolism, as well as the creation of bioinspired or mimetic materials. To develop these projects, the GEC has access to several platforms: molecular biology, electron microscopy, a greenhouse, and an analytical platform. In the latter, MS (LC/MS, GC/MS, and MS/MS) and NMR (300, 400, 500, and 600 MHz with automatic sampler) instruments are available for solid-state and liquid experiments.
In the context of current societal demands, the Unit pays particular attention to applied research and the valorization of the results of its multiple research activities.
Amiens and its surroundings
Amiens is the main town of Picardie, part of Hauts-de-France 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 (Les 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 25000 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.
How to apply
Applications are submitted electronically via the GALAXIE website. Candidates are selected after examination of admissible applications (qualified by the Conseil National des Universités for the position of assistant professeur or equivalence (équivalence) for some foreign PhD).
Selected candidates will be called for an interview in French language. The candidates must be able to speak French at an advanced level, allowing them to undergo the selection interview.
Dates
Apply from March 4th to April 4th 2025 (4 pm, Paris time)
Key dates of the hiring process can be found here.
Start date: September 2025
Three-year PhD position at the Enzyme and Cell Engineering Lab, Amiens, France - NOW CLOSED
Title : Unveiling the mechanism of action of penetrating peptides of the Tachyplesin family against recalcitrant intracellular infections
Scientific context
The interest in molecules that can penetrate infected cells and reach intracellular targets - bacteria, viruses, parasites, or even organelles - is growing rapidly due to their applications in difficult-to-treat diseases such as recalcitrant nosocomial infections or cancer, among others. Nosocomial infections are the direct cause of 4,000 deaths each year in France, with a harmful financial impact on the healthcare system 1,2.
Legionella pneumophila, S. typhimurium, and Mycobacterium tuberculosis are well-known examples of difficult-to-target intracellular pathogens. Similarly, bacteria that are generally extracellular such as S. aureus, E. coli, or Pseudomonas aeruginosa can also grow intracellularly, some forming biofilm-like structures inside host cells, leading to difficult-to-treat recalcitrant infections 3,4.
Many varied strategies are under development to target the intracellular pathogen without harming the host cell. One of these strategies is the use of antimicrobial cell-penetrating peptides (ACPPs), a subtype of antimicrobial peptides (AMPs). AMPs are small proteins with potent antiviral, anticancer, antifungal, antiparasitic, and bactericidal properties 5. They are produced by almost all existing organisms and have gained attention due to their low propensity to induce resistance in their target 5,6. Due to their ability to penetrate cells, some AMPs have demonstrated greater efficacy for killing various intracellular organisms than conventional antibiotics 5, whose intracellular concentrations are lower 6.
Research project
The doctoral thesis project aims to decipher the molecular mechanism by which ACPPs effectively kill intracellular bacteria (such as Staphylococcus aureus, Escherichia coli, and Salmonella typhimurium) in order to refine their properties for pharmacological applications. During this project, the doctoral student will focus on a series of peptides from the tachyplesin family to track their penetration properties using NMR and molecular dynamics techniques, among others. In addition, the collaboration of the GEC with other research teams in the region and internationally will allow the student to learn and use more advanced structural biology techniques, as well as state-of-the-art tissue studies (i.e., DNP-NMR, organ-on-chip).
The laboratory
Research at GEC focuses on cell biochemistry in plants and animals. Transdisciplinary by nature, it combines experience in the preparation of biological membranes with expertise in NMR and computational methods to study the structure and dynamics of biomolecules (all-atom and coarse-grained molecular dynamics, docking, free energy simulations, software development.). Involved in the study of AMPs for several years, GEC hosts the ADAPTABLE database of AMPs. It has privileged access to the high-performance computing platforms in Amiens and Reims (more than 4000 CPU computing cores, 300 GPUs, 500 teraflops). The group has access to molecular biology, electron microscopy, greenhouse and analytical platforms. In the latter, MS (LC/MS, GC/MS and MS/MS) and NMR (300, 400, 500 and 600 MHz with auto-sampler) instruments are available.
Living in Amiens
Amiens, the capital of Picardy, is one hour away from Paris and Lille by train. University students represent more than 25% of its population of 140,000, accounting for a rich cultural life and lively atmosphere. It hosts one of the largest university hospitals in France, powering cutting-edge medical research. Home to the largest gothic cathedral in France (a UNESCO world heritage site) and famous floating gardens, its situation in the Somme valley (with more than 200 km of cycling paths) and the vicinity of the Somme bay (ranked amongst the world’s most beautiful bays) also makes it ideal for nature lovers.
Eligibility
Successful candidates should hold a Master’s degree (or equivalent) in chemistry, physics, molecular biology or related disciplines and possess an intermediate English level. Knowledge or experience in NMR and molecular dynamics will be considered a plus.
How to apply
Applications should be sent to Francisco Ramos Martin (francisco.ramos@u-picardie.fr) and Nicola D’Amelio (nicola.damelio@u-picardie.fr) before June 1st, 2024, comprising:
a curriculum vitae detailing the completed university courses;
grades and ranking sheets for the courses followed during bachelor’s and master’s degrees;
a letter of motivation in which the candidate advertises her/his suitability to the project;
the contact details of at least two of the candidate’s previous supervisors or lecturers willing to recommend their application.
The selected candidate will be required to participate in a competitive selection process between applicants to PhD projects shortlisted by the doctoral school; it is therefore essential that the application file be of high quality. The PhD position will start in October 2024.
References
ASSISTANT PROFESSOR POSITION IN BIOCHEMISTRY (permanent, from September 2024) - NOW CLOSED
An assistant professor position (Maitre de conferences) in biochemistry is offered in Amiens at the University of Picardie Jules Verne (UPJV) in the lab “Enzyme and Cell Engineering, Molecular Recognition and Biocatalysis UMR 7025 CNRS.
Contact : nicola.damelio@u-picardie.fr and catherine.sarazin@u-picardie.fr
Job profile
Research: Structural studies of biomolecules using liquid and solid-state NMR. Studies of interactions between biomolecules and biomolecules in a biomimetic environment (enzymes/lignocellulosic biopolymers, biomimetic membranes, enzymes in nonconventional media). The biomolecules of interest are, on the one hand, amphiphilic molecules such as natural glycolipids derived from various biomasses (microbial or lignocellulosic) with surfactant, elicitor, antifungal, antibacterial and anticancer properties (antimicrobial peptides) and, on the other hand, oligomers generated by the enzymatic depolymerization of lignocellulosic biomass. A complementary approach by light scattering techniques would be greatly appreciated as well as any other complementary techniques. The candidate will have to propose a research project related to this description, specifying its complementarity with the expertise of the team. The candidate will be integrated in projects linking the two main topics of the unit "Plant metabolism and bioresources" and "Biomimicry and biomolecular diversity".
Teaching in biochemistry: The teaching of the biochemistry/microbiology SVT department (Science de la Vie et de la Terre) covers, at the undergraduate level (from L1 to L3), general and structural biochemistry, biological macromolecules, biochemical analysis techniques, and enzymology. Complementary teaching for the Master of Chemistry (speciality biotechnologies of natural resources) is also to be considered: extraction and purification of biological molecules and structural biology. Teaching will be in French, especially at undergraduate level.
Responsibility for teaching units and involvement in innovative pedagogical projects are expected.
Salary
Indications on the salary can be found here.
GEC laboratory in Amiens
The Unit of Enzyme and Cell Engineering, Molecular Recognition and biocatalysis (GEC), has acquired national and international recognition in the field of biotechnology. The GEC develops approaches combining the optimization of bioresource use and plant metabolism, as well as the creation of bioinspired or mimetic materials. To develop these projects, the GEC has access to several platforms: molecular biology, electron microscopy, a greenhouse, and an analytical platform. In the latter, MS (LC/MS, GC/MS, and MS/MS) and NMR (300, 400, 500, and 600 MHz with automatic sampler) instruments are available for solid-state and liquid experiments.
In the context of current societal demands, the Unit pays particular attention to applied research and the valorization of the results of its multiple research activities.
Amiens and its surroundings
Amiens is the main town of Picardie, part of Hauts-de-France 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 (Les 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 25000 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.
How to apply
Applications are submitted electronically via the GALAXIE website. Candidates are selected after examination of admissible applications (qualified by the Conseil National des Universités for the position of assistant professeur or equivalence (équivalence) for some foreign PhD).
Selected candidates will be called for an interview in French language. The candidates must be able to speak French at an advanced level, allowing them to undergo the selection interview.
Dates
Apply from February 22 to March 29 2024 (4 pm, Paris time)
Key dates of the hiring process can be found here.
Start date: September 2024
POST-DOC (6 months, from January 2024)
A 6 month post-doc is offered at the GEC Department, University "Picardie Jules Verne" (UPJV) in Amiens, France, to study the interaction of anti-amyloidogenic peptides with biomimetic membranes
Title of the project: cRossing the blood-brAin barrier for The delIvery Of aNti-AmyLoidogenic peptides with antibactErial activity (RATIONALE)
Referents: Dr. Francisco Ramos-Martin, Pr. Nicola D’AMELIO, Pr. Catherine Sarazin
Contact : francisco.ramos@u-picardie.fr, nicola.damelio@u-picardie.fr, and catherine.sarazin@u-picardie.fr
Laboratory : Unité de Génie Enzymatique et Cellulaire UMR 7025 CNRS, Université de Picardie Jules Verne (UPJV), Amiens, France
Net salary: ~ 2100/month
Summary: Neurodegenerative diseases are mostly associated with the presence of peptides and proteins capable of forming amyloid fibers. Most therapeutic strategies aim at inhibiting their aggregation. The synthetic peptide QBP1 is a promising agent against amyloidogenesis because it is able to inhibit the aggregation of amyloidogenic proteins without showing in-vivo toxicity. QBP1 also displays important sequence similarity with several antimicrobial peptides suggesting an antibacterial activity never studied before.
This collaborative project aims at proposing new effective therapies to fight against neurodegenerative diseases by creating QBP1 analogs capable of crossing the blood-brain barrier and inhibiting the formation of amyloid aggregates while exerting an antimicrobial activity in the brain. From a more fundamental point of view, the project could lead to a better understanding of the role of microbial infections in the initiation and progression of neurodegenerative diseases.
The RATIONALE project. The work is in the frame of the RATIONALE project, in collaboration with the group of Pr. Pascal Sonnet at UPJV and Pr. Fabien Gosselet of Artois University. The project is funded by the MOSOPS project (Projet MOSOPS - Modélisation, Simulation, Optimisation des impacts, des Soins et des Parcours de Santé) presented in collaboration among UPJV, Artois University and University of Littoral Côte d'Opale and funded within the frame of the CPER Santé 2021-2027 (Contrat Contrat de Plan Etat-Région).
Actual work in the frame of the project:
In this project, various peptide derivatives of QBP1 will be studied in their interaction with biomimetic biological membranes, mimicking bacterial lipid composition. Multiple techniques will be used (circular dichroism, fluorescence, molecular dynamics) 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.
The Peptide Biophysics group at GEC laboratory
The GEC laboratory (Enzymatic and Cellular Engineering) is dedicated to the study of cell biochemistry in animals and plants. Within the GEC, the Peptide Biophysics group at UPJV has long experience in the use of NMR for elucidating the structure and dynamics of biomolecules and in the preparation and the modeling of biological membranes, an important part in the development of the project. The group has access to molecular biology, electron microscopy, greenhouse and analytical platforms. In the latter, MS (LC/MS, GC/MS and MS/MS) and NMR (300, 400, 500 and 600 MHz with auto-sampler) instruments are available.
Amiens and its surroundings
Amiens is the main town of Picardie (now part of Hauts-de-France 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 (Les 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 candidate must hold a PhD in biochemistry and/or biophysics and/or chemistry, have a solid background in NMR spectroscopy. Experience in Molecular modeling should also be appreciated. He/she should be able to work both independently and in the group. Knowledge of biochemistry, practical laboratory experience and an intermediate level of English are mandatory.
How to apply
Interested candidates can send applications to nicola.damelio@u-picardie.fr, catherine.sarazin@u-picardie.fr and francisco.ramos@u-picardie.fr including:
- A curriculum vitae.
- A letter of recommendation from the head of the present team and the PhD thesis supervisor.
- 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: 15/01/2024
Start date: mid-January/February 2024
PhD position - NOW CLOSED
Three-year PhD position at the Enzyme and Cell Engineering Lab, Amiens, France
Title : Simulation of the translocation of peptides across biological membranes for future pharmacological applications
Scientific context
Cell-penetrating peptides (CPPs) are small peptides (30 amino acids or shorter) that can cross the outer membranes of cells without affecting their integrity.1 They are able to reach specific cell compartments, where they can potentially facilitate the delivery of therapeutic or imaging-related drugs. The therapeutic potential of CPPs is huge, and still largely untapped despite the recent increase in CPP-derived drugs approved by the Food and Drug Administration. In particular, CPPs could replace traditional antibiotics that have become ineffective against the highly virulent and resistant bacteria of the ESKAPE class, which raise global public health concerns acknowledged by the World Health Organization.2 However, current limitations in the understanding of the interactions between CPPs and membranes strongly hinder the rational design of CPPs, which is crucial to target specific therapeutic applications. The goal of this project is to contribute to a better understanding of the mechanisms and free energy costs driving the recognition and translocation of a set of peptides across membranes, using molecular dynamics simulations.
Research project
Because CPP/membrane recognition and translocation are slow processes, two simulation techniques will be combined to obtain accurate yet computationally cost-effective simulations: coarse-graining, which represents atom groups as pseudoparticles (limiting computational cost), and enhanced sampling, which accelerates transitions along user-defined collective coordinates related to the process under study and yields the associated free energy penalties. These collective coordinates will be carefully chosen to account both for peptide flexibility and membrane deformation, based on previous work in the lab.3 We will especially focus on two crucial phases of the global mechanism: the adsorption of the peptide on the membrane, and the first steps of its translocation through it. The studied peptides will be chosen as variations on the sequence of well-known naturally-occurring CPPs (Tat, penetratin…), as well as exemplars of the main classes of CPPs selected using the ADAPTABLE antimicrobial peptide (AMP) database hosted in the lab.4 Novel hybrid CPPs studied in the lab as part of a collaborative project with microbiologists will also be considered, providing stimulating interactions between experiments and in silico predictions. Beyond the mechanisms specific to each CPP, which are valuable per se, we hope to derive guidelines facilitating the choice of CPP sequences for a given application. If time allows the results of simulation might be supported by experimental techniques (fluorescence, NMR).
The lab
Research at GEC focuses on cell biochemistry in plants and animals. Transdisciplinary by nature, it combines experience in the preparation of biological membranes with expertise in NMR and computational methods to study the structure and dynamics of biomolecules (all-atom and coarse-grained molecular dynamics, docking, free energy simulations, software development...). Involved in the study of AMPs for several years, GEC hosts the ADAPTABLE database of AMPs. It has privileged access to the high-performance computing platforms in Amiens and Reims (more than 4000 CPU computing cores, 300 GPUs, 500 teraflops).
Living in Amiens
Amiens, the capital of Picardy, is one hour away from Paris and Lille by train. University students represent more than 25% of its population of 140,000, accounting for a rich cultural life and lively atmosphere. It hosts one of the largest university hospitals in France, powering cutting-edge medical research. Home to the largest gothic cathedral in France (a UNESCO world heritage site) and famous floating gardens, its situation in the Somme valley (with more than 200 km of cycling paths) and the vicinity of the Somme bay (ranked amongst the world’s most beautiful bays) also makes it ideal for nature lovers.
Eligibility
Successful candidates should hold a Master’s degree (or equivalent) in chemistry, physics, molecular biology or related disciplines and possess an intermediate English level. Knowledge or experience in computational chemistry, molecular modeling and/or computer programming is highly desirable.
How to apply
Applications should be sent to Benjamin Bouvier (benjamin.bouvier@u-picardie.fr) or Nicola D’Amelio (nicola.damelio@u-picardie.fr) before June 1st, 2023, comprising:
a curriculum vitae detailing the completed university courses;
grades and ranking sheets for the courses followed during bachelor’s and master’s degrees;
a letter of motivation in which the candidate advertises her/his suitability to the project;
the contact details of at least two of the candidate’s previous supervisors or lecturers willing to recommend their application.
The selected candidate will be required to participate in a competitive selection process between applicants to PhD projects shortlisted by the doctoral school; it is therefore essential that the application file be of high quality. The PhD position will start in October 2023.
References
1 Lindgren, M. ; Hällbrink, M. ; Prochiantz, A. ; Langel, U. Trends Pharmacol. Sci. 2000, 21, 99–103.
2 Abadi, A. T. B. ; Rizvanov, A. A. ; Haertlé, T. ; Blatt, N. L. BioNanoScience 2019, 9, 778–788.
3 Bouvier, B. J. Chem. Theory Comput. 2019, 15, 6551–6561.
4 Ramos-Martín, F. ; Annaval, T. ; Buchoux, S. ; Sarazin, C. ; D’Amelio, N. Life Sci. Alliance 2019, 2, e201900512.
MASTER INTERNSHIP M2 (6 months, second semester) - NOW CLOSED
A 6 month internship is offered at the GEC Department, University "Picardie Jules Verne" (UPJV) in Amiens, France, to study the interaction of anti-amyloidogenic peptides with biomimetic bacterial membranes
Academic year: 2023-2024
Title of the project: cRossing the blood-brAin barrier for The delIvery Of aNti-AmyLoidogenic peptides with antibactErial activity (RATIONALE)
Supervisor(s): Pr. Nicola D’Amelio, Pr. Francisco Ramos-Martin
Contact : nicola.damelio@u-picardie.fr, catherine.sarazin@u-picardie.fr and francisco.ramos@u-picardie.fr
Laboratory : Unité de Génie Enzymatique et Cellulaire UMR 7025 CNRS, Université de Picardie Jules Verne; Amiens, France
Master 2 fellowship: around 3200 euros for 6 months
Summary: Neurodegenerative diseases are mostly associated with the presence of peptides and proteins capable of forming amyloid fibers. Most therapeutic strategies aim at inhibiting their aggregation. Interestingly, the proteins involved in amyloidogenesis display important similarities with antimicrobial peptides. The synthetic peptide QBP1 is a promising agent against amyloidogenesis because it is able to inhibit the aggregation of amyloidogenic proteins without showing in-vivo toxicity. QBP1 also displays important sequence similarity with several antimicrobial peptides suggesting an antibacterial activity never studied before.
This collaborative project aims at proposing new effective therapies to fight against neurodegenerative diseases by creating QBP1 analogs capable of crossing the blood-brain barrier and inhibiting the formation of amyloid aggregates while exerting an antimicrobial activity in the brain. From a more fundamental point of view, the project could lead to a better understanding of the role of microbial infections in the initiation and progression of neurodegenerative diseases.
Actual work in the frame of the project:
In this project, various peptide derivatives of QBP1 will be studied in their interaction with biomimetic biological membranes, mimicking bacterial lipid composition. Multiple techniques will be used (circular dichroism, fluorescence) with special emphasis on both liquid and solid state NMR and molecular dynamics (MD) simulations. Paramagnetic probes will be used to locate the peptide in the membrane and to determine its structure.
Eligibility
The successful candidate should have a solid background in biochemistry and/or in relative fields involving structural biology or NMR spectroscopy or molecular modelling, be eager to learn and be able to work both independently and in a group. Theoretical knowledge of biochemistry, basic practical experience in the laboratory and an intermediate level of English are mandatory.
How to apply
Interested candidates can send applications to nicola.damelio@u-picardie.fr, catherine.sarazin@u-picardie.fr and francisco.ramos@u-picardie.fr including:
- A 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 first year of master training period.
- 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: 01/15/2024
Start date: mid-January/February 2024
MASTER INTERNSHIP M2 (6 months, second semester) - NOW CLOSED
A 6 month internship is offered at the GEC Department, University "Picardie Jules Verne" (UPJV) in Amiens, France, to study the interaction of anti-amyloidogenic peptides with biomimetic bacterial membranes
Academic year: 2023-2024
Title of the project: The interaction of selective antimicrobial peptides (STAMPs) with the membrane of different bacterial species.
Supervisor(s): Pr. Nicola D’Amelio, Pr. Francisco Ramos-Martin
Contact : nicola.damelio@u-picardie.fr, catherine.sarazin@u-picardie.fr and francisco.ramos@u-picardie.fr
Laboratory : Unité de Génie Enzymatique et Cellulaire UMR 7025 CNRS, Université de Picardie Jules Verne; Amiens, France
Master 2 fellowship: around 3200 euros for 6 months
Aim. The non-specific nature of most antibiotics makes their use deleterious for the human and animal microbiome. By recognising the different composition of bacterial membranes, a subclass of AMPs called STAMPs (selective antimicrobial peptides) can selectively kill bacterial pathogens thus reducing the impact of antibiotics on the microbiome (Figure 1). This thesis will be devoted to unraveling the molecular mechanisms by which STAMPs can selectively interact with specific pathogens exploiting the differences in membrane lipid compositions. It implies studying the interaction by liquid and solid state NMR and molecular dynamic simulations, among other techniques.
Scientific context. The fundamental role of human microbiota, mainly composed of bacteria and bacteriophages [1,2], in metabolic, digestive, immune and even neurological functions is becoming more and more apparent [3]. The use of non-specific antibiotics has deleterious effects on its complex equilibria. In the era of antibiotic resistance, antimicrobial peptides (AMPs) are an appealing alternative to classical antibiotics. They are produced in all life kingdoms and considered part of innate immunity [4]. Even though the mechanism of action of AMPs is multifaceted, a key step of their activity resides in the interaction with the bacterial membrane, often causing its destabilization and/or the formation of lethal pores. While exceptions exist [5], their mode of action is intrinsically not prone to resistance, as demonstrated by their efficacy, optimized by evolution in millions of years.
Although some AMPs are in use [4], their clinical development has been severely limited by the high cost of production and their short half-life in plasma. Recent advances in molecular biology have allowed the development of engineered bacteria, able to produce bioactive molecules in response to stimuli [6]. These include modulating the host’s immune system, sensing and diagnosing disease, altering the host’s metabolism and combating [6–8] pathogens. The latter opens the way to the controlled production of AMPs in situ by engineering commensal bacteria of the target tissue. Such an application would solve at once the problem of AMPs delivery to the site of infection and their production cost, making their short half-life an advantage for their clearance.
The main challenge of the production of AMPs in situ, is the potential toxicity for the producing engineered species and for other beneficial species present in the flora of the target tissue. On the other hand, our body naturally produces AMPs which are safe within their site of expression. In particular, some AMPs can be selective towards specific organisms. Such AMPs are called STAMPs (Selective Target AntiMicrobial Peptides). The lipid membrane composition largely varies among bacterial species [9] and there is evidence that the selectivity of STAMPs is due to the recognition of such diversity [10–13]. Selective targeting of pathogens, unlike large-spectrum antibiotics, further limits the risk of resistance within the microbiota. Despite their great potentiality, STAMPs are relatively unexplored [14–16](and refs therein), although experimental data on their activity can be found spread in different databases.
The project/methodology. For this project we have selected 10 STAMPs each specific for one or more ESKAPE bacteria (E. faecium, S. aureus, K.pneumoniae, A. baumannii, P. aeruginosa and E. coli). The interaction of these STAMPs with various models of biological membranes (micelles, bicelles, nanodisks and liposomes of different sizes) will be studied by liquid and solid state NMR (including 2H and 31P of lipids), fluorescence and molecular dynamic simulations. The determination of the molecular structure of STAMPs in the absence and in the presence of membranes is likely to reveal key interatomic interactions at the basis of their selectivity.
Eligibility
The successful candidate should have a solid background in biochemistry and/or in relative fields involving structural biology or NMR spectroscopy or molecular modelling, be eager to learn and be able to work both independently and in a group. Theoretical knowledge of biochemistry, basic practical experience in the laboratory and an intermediate level of English are mandatory.
How to apply
Interested candidates can send applications to nicola.damelio@u-picardie.fr, catherine.sarazin@u-picardie.fr and francisco.ramos@u-picardie.fr including:
- A 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 first year of master training period.
- 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: 01/12/2023
Start date: mid-January/February 2024
Figure 1. (left) STAMPs (here represented as orange hairpins) selectively kill pathogens (brown bacteria) while leaving STAMP-expressing bacteria (light green) and the rest of the microbiome unaffected. (right) The differences in the minimal inhibitory concentrations (MIC) of STAMPs towards different bacteria depends on the difference in the lipid composition of their membranes. Image created by Biorender.
Page updated
Google Sites
Report abuse