Diploma & Master thesis projects


DNA-based nanoscaffolds for membrane protein reconstitution

Master student:
Naga Suresh Kola
Supervisors:
M. Sc. Madhumalar Subramanian, Prof. Dr. Karim Fahmy (HZDR)
Departement:
Biophysics

Membrane proteins play a vital role in the cellular processes and the functions of these lipid-associated proteins can be elucidated from their structural data. Owing to their hydrophobicity and tendency to aggregate in hydrophilic solution had made it difficult to unravel their structure in-vitro. In order to investigate their fold and functions, membrane proteins are reconstituted into a native phospholipid-like environment called membrane mimetics. However, controlling the size and shape of these in-vitro model systems in a defined way is difficult and challenging. An advent of DNA nanotechnology had leveraged in programming these structures with precise size and dimensions. Our group has developed a novel nano-scaled membrane-mimetic system called DNA-encircled Lipid Bilayers (DEBs) by exploiting the versatile toolbox of DNA nanotechnology. This versatile approach helps to functionalize the lipid bilayer in accordance to the specific needs of biophysical investigations.

Molecular dynamics model of a DEBs composed of a 147 bp dsMC with 28 dodecyl groups and 434 DMPC lipids. DNA ring is represented in white, alkyl chains are in red, and the DMPC head groups are in blue. (Abbildung aus Iric, K., et al. (2018). DNA-Encircled Lipid Bilayers. Nanoscale. 10. 10.1039/C8NR06505E.) ©Copyright: Thorsten Lars-Schmidt

Molecular dynamics model of a DEBs composed of a 147 bp dsMC with 28 dodecyl groups and 434 DMPC lipids. DNA ring is represented in white, alkyl chains are in red, and the DMPC head groups are in blue. (Abbildung aus Iric, K., et al. (2018). DNA-Encircled Lipid Bilayers. Nanoscale. 10. 10.1039/C8NR06505E.)

Foto: Thorsten Lars-Schmidt

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DEBs are made of multiple copies of alkylated oligonucleotides hybridized into a double-stranded minicircles (dsMC). Upon addition of lipids to the dsMC, the alkyl chains of the minicircles stabilizes the hydrophobic rim of lipid bilayer and self-assembles it inside the minicircles. Though the theoretical possibility of an alkylated DNA ring stabilising a lipid bilayer has been proved, still the main purpose of stabilising a membrane protein in-vitro has to be proved. In my master thesis, I intend to accomplish the reconstitution of a membrane protein inside DEBs and further also contribute to the improvement of the DEBs assembly as it is still in its infancy.