Computer Aided Design of Synthetic Viruses

This 3 year PhD research project, due to start at the end of Sep 2017, is a collaboration between the Biomolecular Modelling (FLG) and Molecular Bionics groups(GB) (www.battagliaresearchgroup.com) Chemistry Department and Institute of Structural and Molecular Biology at UCL.
The shape and superficial patterns of viruses present a unique inspirational source to produce complex self-assembled structures that are able to effectively enter living cells and overcome biological barriers (as the blood-brain barrier). The significant advantage of building virus-inspired self-assembled vesicles from designed peptides is that they would be biodegradable, biocompatible and have the capability of (i) improving existing therapies and/or (ii) enable new ones.
The aim of this PhD project is to use atomistic and coarse-grained molecular dynamics simulations together with enhanced-sampling algorithms to design novel artificial peptides that are able to self-assemble in biomimetic nanoparticles. The multiscale models will be used to determine how the size, topology, topography and surface chemistry of the nanoparticles are determined by the peptide sequence and properties. Within the GB group the knowledge gained by the simulations will be used to synthesize the different components hierarchically. At the molecular level, the single building blocks can be synthesised using both solid-phase synthesis or recombinant methodology. At the supramolecular level, the different structures will be formed in water using advanced multiphase mixing units and/or microfluidics. The final structures will be fully characterised using a combination of advanced microscopy (including a new liquid Scanning Transmission Electron Microscopy STEM just acquired by the department), scattering techniques (DLS and MALS) and small angle x-ray scattering (SAXS) and spectroscopic techniques (NMR, Fluorescence, Circular Diachronism and UV/Vis).
The new particles will be also tested by GB’s group in vitro and in cells to assess their capability of achieving effective selectivity, endocytosis and subsequent payload delivery.
This ambitious project will combine cutting-edge molecular and mesoscale simulations with aqueous self-assembly and advanced characterisation techniques. The outcomes of the proposed research will yield crucial insights into the chemical principles of biological organisation and provide cutting-edge drug delivery systems for the treatment of cancer, neurological and immunological disorders.
This studentship offers an excellent opportunity for a gifted individual to work on a significant, novel and exciting problem in biophysics and will allow them to learn about molecular simulations, coding, computational method development as well as electron microscopy and other advanced biophysical techniques under the supervision of well-known experts in the field.

Please submit a full CV and covering letter to Professor Francesco L. Gervasio (f.l.gervasio(at)ucl.ac.uk). The Deadline for applications is 1st of July 2017or as soon as the position is filled.