COFUND PhD position – Biomedical engineering

Title of the thesis project: Development of bio-based antiviral materials based on biopolymers and marine bacteria-derived compounds for biomedical applications

Scientific Context

Viruses continue to pose a significant threat to global public health, being one of the leading causes of mortality worldwide, responsible for millions of deaths every year, as exemplified by recent pandemics. The primary approach to clinical antiviral therapy involves the use of antiviral drugs alongside symptomatic treatments. However, significant side effects from antiviral drugs, such as gastrointestinal, liver, kidney, or hematopoietic issues, can impact patient adherence and potentially disrupt treatment. Additionally, frequent viral mutations and the limited scope of single antiviral mechanisms can result in drug resistance, often causing therapeutic failure. The incorporation of biomaterials, such as alginate and chitosan, into antiviral therapy offers distinct benefits and novel mechanisms of action. Antiviral biomaterials function through a variety of mechanisms, including physically adsorbing viruses, interference with the virus–cell interaction by binding to the viruses as entry inhibitors, inducing irreversible viral deformation, interfering with viral nucleic acid replication, and preventing the release of viruses from infected cells, among other mechanisms. The capture of viruses through virus– biomaterial interactions and the disruption of viral structures via applied forces represent distinctive antiviral mechanisms of biomaterials. Therefore, biomaterial-based antivirals further offer new mechanisms and reduce the risks of developing drug resistance, which can be observed widely in molecular antivirals. In this regard, numerous biomaterials are being designed in combination with antiviral drugs against a range of viral infections. Interestingly, various biomaterial formulations have demonstrated higher efficiency in inhibiting viral nucleic acid replication compared to conventional antiviral drugs. Therefore, there is an urgent demand for novel antiviral materials that offer effective prevention and control of viral infections, especially in the context of biomedical applications. 

The marine environment represented a largely unexplored habitat. Due to the abundance and chemical composition of marine compounds, this environment represents a significant reservoir of original biomolecules. Marine species, both prokaryotes and eukaryotes, synthesize numerous metabolites belonging to various structural classes, such as sugars, pigments, lipids, proteins, polyketides, alkaloids, steroids, etc. The biological activity of these compounds is highly promising for the development of new drugs derived from natural marine organisms. Among these original compounds, some are derived from marine bacteria, which are a rich source of molecular diversity. Their adaptation to extreme and often competitive environments promotes the development of specific metabolites. As a result, these bacteria remain among the most promising microorganisms for the discovery of new molecules with unique properties, including antimicrobial, anticancer and antiviral activities. Therefore, marine bacteria represent a promising and underexplored source of bioactive metabolites with potential antiviral properties.

By leveraging these metabolites and combining them with biocompatible biopolymers like alginate and chitosan, this PhD thesis project aims to develop antiviral materials capable of mitigating viral infections while maintaining safety and functionality in biomedical contexts.

Scientific Objectives

The main objective of this PhD thesis is to develop, characterize, and evaluate antiviral materials for biomedical applications using bioactive metabolites extracted from marine bacteria from La Rochelle Collection. The specific objectives are as follows:

1. Isolation and identification of antiviral metabolites by extracting and characterizing bioactive compounds with antiviral activity from marine bacterial cultures.
2. Formulation of antiviral materials by developing composite materials by incorporating the identified metabolites into alginate and chitosan matrices, ensuring uniform distribution and stability of the bioactive agents.
3. Evaluation of antiviral efficacy by assessing the antiviral activity of the developed materials against a range of viral pathogens, with emphasis on clinically relevant strains.
4. Characterization of material properties by evaluating the physicochemical, mechanical, and biocompatibility properties of the developed antiviral materials to ensure they meet biomedical standards.
5. Mechanistic studies by investigating the mechanisms underlying the antiviral activity of the developed materials to elucidate their modes of action.

Scientific Challenges

The project entails several scientific challenges:

1. Extraction and stability of marine-derived metabolites by ensuring efficient extraction, purification, and stability of bioactive metabolites from marine bacteria, while maintaining their antiviral efficacy during processing and integration with polymers.
2. Material formulation and uniformity by achieving homogeneous integration of antiviral agents within alginate and chitosan matrices to ensure consistent antiviral effects while preserving mechanical and biocompatibility properties.
3. Viral testing and safety assessment by conducting rigorous antiviral assays, while ensuring the developed materials are non-toxic and safe for biomedical applications.
4. Optimization of material properties by balancing antiviral efficacy with essential properties such as biodegradability, mechanical strength, biocompatibility, and processability to meet the diverse needs of biomedical applications.

Methods Chosen to Address Challenges

1. Extraction and characterization of marine bacterial cultures will be subjected to optimized extraction protocols, and bioactive metabolites will be characterized using analytical techniques such as HPLC, mass spectrometry, and NMR spectroscopy.
2. Material synthesis of the extracted metabolites will be incorporated into alginate and chitosan matrices through methods such as solvent casting, crosslinking, and freeze-drying techniques to produce homogenous composites with controlled release properties.
3. Antiviral assays to determine the antiviral efficacy by using the double-layer method.
4. Physicochemical and mechanical characterization by TGA, DSC and FTIR spectroscopy, FESEM, mechanical testing, and biodegradability assays will be used to characterize the developed materials.
5. Biocompatibility testing through cytotoxicity assays, following ISO-10993 standards on fibroblast L929 and keratinocyte HaCaT cells, to ensure they are safe for potential biomedical applications.
6. Mechanistic studies to explore interactions between viral particles and the bioactive metabolites within the materials, using molecular docking during the three months secondment with a non-academic actor (ProtoQSAR).

Expected Results

• Development of antiviral material by integrating marine-derived bioactive metabolites into alginate and chitosan matrices.
• Broad-spectrum antiviral activity against a range of viral pathogens, with the potential for use in a variety of biomedical applications.
• Production of biocompatible and functional materials with desirable mechanical, physicochemical, and biocompatibility properties suitable for biomedical applications.
• Insights into the molecular mechanisms of antiviral action, paving the way for the rational design of future antiviral materials.
• This project represents a pioneering effort to combine marine-derived bioactive compounds with biocompatible polymers, aiming to produce antiviral materials with broad applications in biomedicine. It holds promise to address unmet needs in combating viral infections through innovative and sustainable solutions.

Since its creation in 1993, La Rochelle University has been on a path of differentiation.

Thirty years later, as the university landscape recomposes itself, it continues to assert an original proposition, based on a strong identity and bold projects, in a human-scale establishment located in an exceptional setting.

Anchored in a region with highly distinctive coastal features, La Rochelle University has turned this singularity into a veritable signature, in the service of a new model. Its research it addresses
the societal challenges related to Smart Urban Coastal Sustainability (SmUCS).

The new recruit will join the Littoral, Environment and Society laboratory (LIENSs).

Cotuelle: Catholic University of Valencia (UCV), Spain. Biomaterials and Bioengineering Laboratory.

Research Field: Biological sciences

Education Level: Master Degree or equivalent