Thesis topic proposal
Csaba Pál
Toward resistance-free antibiotics with biomimetic approaches


Institute: University of Szeged
theoretical medicine
Theoretical Medicine Doctoral School

Thesis supervisor: Tamás Martinek
co-supervisor: Csaba Pál
Location of studies (in Hungarian): SZTE GYTK Gyógyszeranalitikai Intézet
Abbreviation of location of studies: GYTK

Description of the research topic:

Fighting against antibiotic resistance is a great current challenge. Spontaneous mutations and horizontal gene transfer result in complex bacterial response with increasing frequency, which decrease the efficacy of the existing antibiotics. Our goal is to construct compounds that are rationally designed to evade bacterial evolutionary mechanisms producing the antimicrobial resistance. We build on systems biology results including patterns of cross-resistance and collateral sensitivity observed among selected antibiotics. Our approach utilizes mimetics of antimicrobial peptides (short peptides with a broad spectrum of antibacterial activities). Such peptides are found among all classes of life, and are part of the defence mechanisms against microbial pathogens. Because antimicrobial peptides have diverse chemical features and cellular targets, they are promising antibacterial agents and offer excellent templates to construct biomimetic foldamer candidates. Small molecules are also part of the toolbox. Careful selection and charaterization of bacterial targets is carried out by means of molecular and structural biology, which is supported by molecular modeling. The methodology includes rational design of candidate molecules relying on the toolbox of in silico design, synthesis, biophysical and structural characterizations of compound-target interactions. We expect new methodologies, tailor made foldamers and foldamer-small molecule combinations as output, which successfully supress bacterial resistance mechanisms.

Required language skills: english
Number of students who can be accepted: 1

Deadline for application: 2019-12-31

All rights reserved © 2007, Hungarian Doctoral Council. Doctoral Council registration number at commissioner for data protection: 02003/0001. Program version: 2.2358 ( 2017. X. 31. )