Thesis supervisor: Gyula Batta
Location of studies (in Hungarian): Building of Chemistry Abbreviation of location of studies: E-18,
Description of the research topic:
Resistance of microorganisms against commercially available antimicrobial agents is growing and threatens with epidemics in the 21st century. Antifungal disulfide miniproteins, are potentially useful e.g. against Aspergillosis, with fatal outcome in immunocompromised patients. We have a long research history in this topic. These small proteins are produced by fungi, like Penicillium chrysogenum, have 50-60 residues, and their -barrel like structures are maintained with several covalent disulfide bonds. They are harmless for mammalian cells, however they selectively kill other fungal strains. We have successfully determined the tertiary structures of some representatives in solution, by NMR (PAF, pdb: 2MHV, sfPAFB pdb: 2NC2, NFAP pdb: 5OQS). However, their mode of action is unclear until now at a molecular level. PhD student on the project will be familiar with up to date multidimensional protein NMR techniques for assignment and evaluation of the spectra, that ultimately leads to the structures of new members of this protein family. Some protein expression work (wet lab) might be necessary, to produce stable isotope labelled proteins for NMR. The planned NMR conformational dynamics and unfolding studies may help to disclose hidden states for understanding their mode of action. In addition, search for interacting partnes will be carried out using bioinformatics, LC-MS and ITC screening with the lysates of sensitive non-pathogenic fungi. Stability will be studied using chemical denaturation with DSC monitoring. We are focussing now on new antifungal proteins belonging to the phylogenetically distinct ”bubble-protein” (PAFC and NFBP), and the anti-yeast (NFAP2) groups. More importantly, new antimicrobial potential of these proteins were discovered, e.g. the recently published NFAP2 has anti-candidal, and PAFB showed antiviral activity. In our project we aim to disclose the structural dynamics of the three new proteins and we attempt to understand their molecular mode of action in comparison with some PAF-like proteins.
Required language skills: english Further requirements: Chemistry or Biology MSc. and practical knowledge of analytical chemistry, biochemistry and possibly NMR
Number of students who can be accepted: 2
Deadline for application: 2021-05-17
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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