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Thesis topic proposal
 
László Norbert Galgóczi
Drug repurposing according to mechanism of action of an antifungal protein to inhibit Candida biofilms

THESIS TOPIC PROPOSAL

Institute: University of Szeged
biology
Doctoral School of Biology

Thesis supervisor: László Norbert Galgóczi
Location of studies (in Hungarian): University of Szeged, Faculty of Science and Informatics, Department of Biotechnology
Abbreviation of location of studies: SZTE


Description of the research topic:

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 language skills: English
Further requirements: 
Basic knowledge in microbiology, protein works and bioinformatics.

Number of students who can be accepted: 1

Deadline for application: 2024-08-31


2024. IV. 17.
ODT ülés
Az ODT következő ülésére 2024. június 14-én, pénteken 10.00 órakor kerül sor a Semmelweis Egyetem Szenátusi termében (Bp. Üllői út 26. I. emelet).

 
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