Ongoing projects

Antifungal proteins - Investigation of antifungal mechanism and biological role for new therapeutic approaches (OTKA FK 134343)

Principal Investigator: László Galgóczy
Duration: 48 moths (2020-2024)

In the consequence of the emerging number of drug-resistant fungal strains the incidences of fungal infections dramatically increased worldwide. The facts that only a few classes of antifungal drugs are available and that they can cause serious side-effects and damage the host’s organs permanently hamper patient management. Therefore, there is a substantial demand for development of fundamental new, effective and safely applicable antifungal strategies to prevent and treat fungal infections.

The features of the small molecular weight, cysteine-rich, cationic antifungal proteins secreted by the filamentous ascomycete, Neosartorya (Aspergillus) fischeri (crAFPs) correspond well to these challenges. One of the key steps in their application as antifungals drugs is an understanding the molecular mechanisms behind the antifungal activity.
The present project focuses to this aspect, (1) investigation of their antifungal mechanism in human pathogenic fungi and biological role in the native producer, and (2) identification the molecular components of these mechanisms. Furthermore, to (3) identify or design potential drug candidate compounds acting on these molecular components, and (4) prove their safe applicability in the clinical therapy.

These goals will be achieved by young and senior scientists, and supervised university students applying a multidisciplinary approach that integrates transcriptome meta-analysis, virtual ligand screenings and docking techniques, antifungal and toxicity tests.

As a final outcome of the accomplished project, we will be able to make suggestions for a new and effective crAFP target-based antifungal strategy.

Supported by Hungarian National Research, Development and Innovation Office.

Biofungicide and bioactivator potential of novel defensin-like proteins from Solanum lycopersicum L. (OTKA PD 134284)

Principal Investigator: Liliána Tóth
Duration: 36 moths (2020-2023)

As a consequence of the worldwide increase of enormous crop losses by pesticide resistant plant-pathogenic fungi, there is a substantial demand to develop new antifungal strategies in
agriculture to support the increasing global calorie consumption in the next decades.

Antifungal proteins and peptides, including plant defensins are already considered as potential biofungicides; however, several factors still limit their direct topical agricultural application to treat of prevent fungal infections. These limitations are the high costs of production, narrow antifungal spectrum, and potential detrimental effects on plant development and human/animal health.

The present project aims at proving the safe and effective applicability of novel defensin-like proteins from tomato plant (Solanum lycopersicum L.) and their rational designed γ-core peptide derivatives as biofungicide agents in plant protection by investigating their antifungal efficacy against plant pathogenic filamentous fungi and the toxicity against different human cell lines
and plant seedling; furthermore, their application as protective or therapeutic agents against fungal infections on plants leaves and roots. The cost-effective heterologous production of these tomato plant-derived defensins applying a fungal expression system is also in the focus of present project.

In addition, present project aimed to reveal the antifungal mechanisms of these defensins in sensitive fungi, and their potential bioactivator role in the host to trigger the self-defence mechanisms
or modulate the plant development as responses to fungal infection.

Supported by Hungarian National Research, Development and Innovation Office.