Methodology for Development of Synthetic Molecular Machines - Biophysical Limitations and Possibilities

Lead Research Organisation: University of Oxford
Department Name: Oxford Physics

Abstract

The project aims to further the understanding of the structure and operation of biological molecular machines and to explore the opportunities of developing them synthetically as well as enhancing and altering their original functions.

A meta-study of known types of biological molecular machines (e.g. the bacterial flagellar motor [BFM], myosin, dynein, kinesin, DNA- and RNA-polymerase, ion channels etc.) will be done together with their operation mechanisms aiming to determine biophysical principles (e.g. low Reynold's number environment or energy confluence at nanoscale) imposing limits on their structural functionality.

Current and potential future methods of engineering synthetic molecular machinery (including molecular motors, propellers, switches, shuttles, tweezers, logic gates, rotaxanes and catenanes) will be determined including bottom-up approach (self-assembly, molecular synthesis, guided molecular evolution, single atom manipulation, molecular 3D printers etc.) and top-down approach (nanolithography, genetic modification of cells etc.). Ways of supplying energy and controlling their operation (e.g. via magnetic or electromagnetic fields) will also be researched.

The work will be supported by experimental research on the BFM and the intricacies of its operation, the torque generation at the rotor/stator interface, the variations in step size, the on and off operation of stators, load dependence, mutations, reason for clockwise / counter clockwise rotation direction change, possibility of artificial assembly and control. Novel methodology will utilize the use of ultrafast dark field microscopy and gold nanoparticles markers.

Invention of a methodology for synthesising nanomachines with desired functionality could mean a revolution for medicine and material manufacturing industry similar to the one brought to computing by the invention of semiconductor transistors or to microbiology by the invention of a microscope. In medicine, the synthetic molecular machinery could allow for selective cell targeting and drug delivery or minimally-invasive surgery combating cancer or cardiovascular diseases. Nanorobots would provide unmatched performance for manufacturing 3D nanomaterials and structures e.g. for 3-dimentional IC chips as well as offer ultra-precise manipulation of matter at atomic level in scientific equipment.

It falls within the EPSRC "Biophysics and Soft Matter Physics" research area listed within the "Physical Sciences" theme as well as within "Manufacturing the Future" theme."

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509711/1 01/10/2016 30/09/2021
1947239 Studentship EP/N509711/1 01/10/2017 30/09/2020 Michal Wojcicki