Thesis topic proposal
Ferenc Vonderviszt
Development of flagellin-based artificial binding proteins for diagnostic applications


Institute: University of Pannonia
material sciences
Chemical Engineering and Material Sciences Doctoral School

Thesis supervisor: Ferenc Vonderviszt
Location of studies (in Hungarian): University of Pannonia
Abbreviation of location of studies: MÜKKI

Description of the research topic:

Biosensors and protein-chips usually apply antibodies as recognition elements. However, these proteins are expensive, poorly stable and hard to produce. It is highly desirable to replace antibodies with other kind of sensing molecules. Flagellin, the subunit protein of bacterial flagellar filaments, is a protein polymerizable to form long filaments. The major objective of this project is to develop a technology to engineer the central variable portion of flagellin to give it specific molecular recognition functionality, and to use these modified flagellins to build filamentous nanostructures. These filamentous receptor structures may serve as basic recognition units for biological sensors and diagnostic kits applicable in medical diagnostics, environmental monitoring or food quality control.
Novel flagellin-based binding proteins against various target molecules will be fabricated by engineering the hypervariable D3 domain of flagellin or replacing it by known binding domains/motifs, in a way preserving polymerization ability. D3 will be used as a scaffold, and the amino acid sequence of its L1-L3 surface loop regions will be randomly modified to create a huge number of mutants displaying different binding sites. Variants capable of binding the desired target molecules will be selected by ribosome display technology. They will be cheaply produced in bacteria in large quantities. Due to their polymerization ability, flagellin-based binding proteins will be used to build functionalized flagellar nanotubes of a desired length with a very high binding site density on their surface. Their binding properties will be characterized and their applicability as sensing elements will be explored.

Bereczk-Tompa E, Vonderviszt F, Horvath B, Szalai I, Pósfai M (2017) Biotemplated synthesis of magnetic filaments. Nanoscale 9, 15062-15069.
Bereczk-Tompa E, Pósfai M, Tóth B, Vonderviszt F (2016) Magnetite-binding flagellar filaments displaying the MamI loop motif. ChemBioChem 17, 2075-2082.
Klein A, Szabo V, Kovacs M, Patko D, Toth B, Vonderviszt F (2015) Xylan-Degrading Catalytic Flagellar Nanorods. Mol. Biotech. 57, 814-819.

Further requirements: 
Requirements: good command of English; solid background in molecular biology

Number of students who can be accepted: 1

Deadline for application: 2018-06-30

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