Our colleague Soumya from Bionanoscience and Biochemistry Laboratory at the Malopolska Centre of Biotechnology, Krakow, Poland, is looking for a new PhD student for his project 'A Programmable Modular, Molecular “Ball-and-Glove” with Potential for Drug Delivery' (description below). Application deadline 15 August.
This study aims to design and develop a molecular “ball and glove” consisting of a designed DNA origami hemisphere (“glove”) capable of holding a ferritin-based, hollow cage-protein nanosphere (“ball”). The successful design will enable us to carry out two important fundamental research goals simultaneously, these are: firstly, solving the problem of breaking the protein symmetry of multimeric protein assemblies and secondly, construction of higher order, complex nanometric structures for use as “smart” drug delivery systems. The individual goals of the research are: i) To design a DNA origami “glove” capable of binding and partially enveloping a ferritin protein cage; ii) To use the produced “ball and glove” structure to allow modification of only one hemisphere of the protein cage (symmetry breaking). iii) Filling of the ferritin “ball” with its natural ligand, Fe2O3, to produce magneto-ferritin, which has potential application in MRI imaging, iv) filling of the ferritin cage with the anti-cancer agent doxorubicin; iv) Addition of targeting moieties to the DNA origami glove to endow it with programmable targeting capability, specifically, the addition of G-quadruplex DNA aptamers for targeting to cancer cells through nucleolin binding and v)
initial testing of delivery of the assembled biological nanomachine whereby a programmable DNA origami “hand” targets a cancer cell a delivers to it either a magnetoferritin (for imaging) or a doxorubicin drugloaded ferritin (for therapy).
Impact of the Research
The research offers the prospect of signify advancement both in i) advancement of basic bionanoscience capabilities and ii) progress towards new smart systems for attacking cancer. For i) the ability to modify a useful protein nanosphere in its natural state with symmetry breaking alterations presents a completely new tool for the bionanoscientist`s construction kit toolbox. For ii) we propose a complex nanoscale system that is programmable – a first step towards adaptive therapeutics that may be able to “outwit” resistant targets. Furthermore the system is modular with logic components being interchangeable while core structure and cargos can be reused. We expect this system to be a foundation for a new field of complex, programmable hybrid therapeutic nanosystems.
More info about the position here and here.