PhD Topics

Drug repurposing according to mechanism of action of an antifungal protein to inhibit Candida biofilms

As a consequence of the increasing number of fungal infections caused by antifungal drug-resistant Candida biofilms, there is an urgent need to develop new and effective biofilm inhibitory strategies against the most prevalent clinically important species, such as Candida albicans and Candida auris. The Neosartorya fischeri antifungal protein 2 (NFAP2) is considered as a potential candidate for this purpose as it shows inhibitory and eradication activities on Candida biofilms.

However, development of an NFAP2-based anti-biofilm drug is cost- and time-consuming. Drug repurposing represents a time- and cost-effective straightforward strategy for identification of new applicability of existing drugs beyond the original medical indication.

The announced PhD project focuses on these aspects, and aims to (1) investigate the biofilm inhibitory mechanism of NFAP2 in C. albicans and C. auris, (2) identify the direct and indirect molecular components of the Candida biofilm inhibitory activity of NFAP2 to find protein targets for a drug repurposing strategy, (3) identify NFAP2 binding pockets of the directly targeted proteins, and search for molecules with binding affinity to these pockets from approved drug, experimental drug and traditional Chinese medicine libraries, (4) investigate the potential, safe, and future-proof applicability of the most promising candidate molecule.

These goals will be achieved with a multidisciplinary approach that integrates protein localization investigation, transcriptome analysis, whole genome sequencing, in vitro protein-protein interaction analysis, in silico protein-protein docking, structure-based virtual screening, antifungal susceptibility testing, laboratory microevolution, acute toxicity testing. As a final outcome of the project, we will be able to make suggestions for a new and effective Candida biofilm eradication strategy for the medicine.

Required skills:
Good communication in English. Basic knowledge in microbiology, protein works and bioinformatics.



The possibility of resistance development to antifungal proteins in fungi

In spite of the emerging number of life-threatening fungal infections with high mortality rate caused by drug-resistant strains, and the fact that the recently applied prolonged antifungal therapies can seriously damage the host’s organs, the initiation to develop effective and safely applicable new antifungal drugs is still neglected for human welfare.

The already intensively studied antifungal proteins from filamentous Ascomycetes and their functional peptide derivatives show high fungal-specificity and antimicrobial efficacy, thus they represent promising candidates to develop fundamental new antifungal therapeutic strategies to overcome global antifungal challenges. Although, knowledge about the potential of fungi to develop resistance mechanism to antifungal proteins, and about the influence of antifungal protein resistance mechanisms on the physiology of fungi is still limited which hampers their application as potential new antifungal drugs.

The announced PhD project focuses to these aspects. These goals will be achieved with a multidisciplinary approach that integrates laboratory microevolution, metabolic fitness investigation, abiotic and biotic stress factor tolerance analyses, genome sequencing, transcriptome meta-analysis, virulence analysis, antifungal susceptibility testing, recombinant protein expression, and peptide synthesis.

The accomplishment of present project provides the first step toward new fungal-specific drug development not just in the medical treatment, but also in the pest control and food preservation with worldwide economic and societal impact.

Required skills:
Basic knowledge in microbiological and protein works. Basic bioinformatics knowledge.



Potential of novel defensin-like proteins from Solanum lycopersicum L. in sustainable agriculture

As a consequence of the worldwide increase of enormous crop losses by pre- and postharvest pesticide resistant phytopathogenic fungi, there is a substantial demand to develop new antifungal strategies in agriculture and food industry to support the increasing global food consumption in the next decades.

Antifungal plant defensins are already considered as potential biofungicides; however, several factors still limit their direct agricultural application. These limitations are the high costs of production, narrow antifungal spectrum, and potential toxic effects on plant and humans/animals.

The announced PhD research project aims at proving the safe and effective applicability of novel defensin-like proteins from tomato plant (Solanum lycopersicum L.) and their rational designed peptide derivatives as biofungicides in plant protection by investigating their antifungal efficacy against phytopathogenic fungi and the toxicity on different human cell lines and plant seedling; furthermore, their application as protective or therapeutic agents against fungal infections on plant leaves and roots.
The cost-effective production of tomato plant defensins applying a fungal expression system is also in the focus of the project. In addition, present project aimed to reveal the antifungal mechanisms of these defensins in sensitive fungi, and their potential biostimulator role in the plants to trigger the self-defence mechanisms or modulate the plant development as responses to fungal infection.

The accomplishment of present project provides the first step toward new fungal-specific biofungicide development in the pest control and food preservation with worldwide economic and societal impact.

Required skills:
Basic knowledge in microbiological and protein works. Basic bioinformatics knowledge.