Batta Gyula
Structure, dynamics, and stability of small disulfide proteins with antimicrobial targets as investigated by NMR and microcalorimetry methods


Intézmény: Debreceni Egyetem
biológiai tudományok
Juhász-Nagy Pál Doktori Iskola

témavezető: Batta Gyula
helyszín (magyar oldal): DE Kémiai Épület E-18, B-13
helyszín rövidítés: DEKÉ

A kutatási téma leírása:

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.

Laboratory and equipment: we have Bruker AVANCE II.-500 and Bruker NEO-700 - prodigy NMR spectrometers, and a protein wet lab for protein expression work extended with microcalorimeters, ITC-200 and automatic capillary VP-DSC from Microcal/Malvern.

1.Huber, A. ; Galgóczy, L. ; Váradi, G. ; Holzknecht, J. ; Kakar, A. ; Malanovic, N. ; Leber, R. , Koch, J. ; Keller, M.A. ; Batta, G. et al. Two small, cysteine-rich and cationic antifungal proteins from Penicillium chrysogenum: A comparative study of PAF and PAFB, BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 1862, 183246 (2020) 10.1016/j.bbamem.2020.183246

2. Alex, Jimi M. ; Rennie, Martin L. ; Engilberge, Sylvain ; Lehoczki, Gábor ; Hajdu, Dorottya Zsuzsanna ; Fizil, Ádám ; Batta, Gyula ; Crowley, Peter B.: Calixarene-mediated assembly of a small antifungal protein IUCRJ 6 : 2 pp. 238-247. 10 p. (2019)

3. A. Huber, D. Hajdu, D. Bratschun-Khan, Z.Gáspári, M. Varbanov, S. Philippot, Á. Fizil, A.Czajlik, Z. Kele, C. Sonderegger, L. Galgóczy, A. Bodor, F. Marx, G. Batta, New antimicrobial potential and structural properties of PAFB: a cationic, cysteine-rich protein from Penicillium chrysogenum Q176, Scientific Reports, 8, 1751 (2018)

a kutatás fedezete: saját bevételek (CLYCOM, TEVA)
előírt nyelvtudás: angol
további elvárások: Chemistry or Biology MSc. and practical knowledge of analytical chemistry, biochemistry and possibly NMR

előírt nyelvtudás: angol
ajánlott nyelvtudás (magyar oldal): english
felvehető hallgatók száma: 1

Jelentkezési határidő: 2021-05-17

2021. V. 01.
ODT online ülés
Az ODT következő, online ülésére 2021. május 21-én 10.00 órakor kerül sor.

Minden jog fenntartva © 2007, Országos Doktori Tanács - a doktori adatbázis nyilvántartási száma az adatvédelmi biztosnál: 02003/0001. Program verzió: 2.2358 ( 2017. X. 31. )