The EPSRC Centre for Doctoral Training in Cross-Disciplinary Approaches to Non-Equilibrium Systems (CANES) has two fully-funded four-year PhD projects that are co-sponsored by the National Physical Laboratory for Sept. 2015 entry: 1) De novo peptide self-assembly for antimicrobial and gene delivery strategies 2) Interdisciplinary approach to designing stealth peptide capped gold nanoparticles. The projects are summarised below.
The CANES training programme consists of a first year combining taught courses and research projects, leading to the award of an MSc. In years two to four, the programme will include open question sandpits, master classes, journal clubs and an annual retreat. Students will also be able to undertake internships at a broad range of industrial and international academic partners. For further information on the 4 year programme please see here: http://www.kcl.ac.uk/innovation/groups/noneqsys/STUDY/CANES-Training-Programme/Index.aspx . Funding for CANES students covers course fees, a stipend for living expenses (ca. £16,000 per year), and conference travel and internship funds. The programme can support UK applicants as well as a limited number of students from the EU. ------------------------ De novo peptide self-assembly for antimicrobial and gene delivery strategies 1st Supervisor: Prof. Franca Fraternali, Randall Division of Cell & Molecular Biophysics, KCL 2nd Supervisor: Dr. Chris Lorenz, Department of Physics, KCL & Dr. Max Ryadnov, Biotechnology Group, NPL Peptide self-assembly is being exploited for the construction of nano-to-micro scale assemblies from the bottom up. Peptides can be readily made and their sequences are structurally amendable to support specialist functions ranging from tissue repair to antimicrobial activity. Establishing the physicochemical determinants that underlie peptide self-assembly as a process and a tool is an essential step towards novel applications in biomedicine. Combining computational methods with experimental biophysical approaches provides a powerful strategy for the development of a framework aiding in the better understanding of mechanisms behind the formation of self-assembled structures and in their designs possessing selected properties. In this context, researchers from the National Physical Laboratory (NPL) led by Max Ryadnov apply the principles of de novo protein design to construct artificial peptide sequences that assemble into novel macromolecular architectures with different functions enabling intracellular delivery and antimicrobial activity. These are experimental designs but are best described using computer molecular dynamics simulations which allow deciphering, with atomistic precision, the exact self-assembly mechanisms. Importantly, interactions in a specific environment in which the designed peptides and their assemblies exploit their function can be modelled and detailed in silico. In this project we will demonstrate how the first design principles of self-assembling peptides can be used and computationally prescribed to lead to novel and efficient antimicrobial and gene delivery strategies. Please see www.kcl.ac.uk/canes for further details of how to apply. Interested candidates should apply by 20 February if at all possible. Late applications will be considered as long as places remain, provisionally until 20 March. Informal enquiries can be addressed to the CANES Centre Manager (ca...@kcl.ac.uk) ------------------------ Interdisciplinary approach to designing stealth peptide capped gold nanoparticles 1st Supervisor: Dr. Chris Lorenz, Department of Physics, KCL 2nd Supervisor: Prof. Franca Fraternali, Randall Division of Cell & Molecular Biophysics, KCL & Dr. Max Ryadnov, Biotechnology Group, NPL Nanoparticle-based technology has many biomedical applications including drug delivery, biosensing, diagnostics and imaging. In all cases, the nanoparticles must be capped appropriately to render them biocompatible, functional and stable against aggregation in biological systems. Most nanoparticles that are introduced into the bloodstream are susceptible to opsonisation (the process by which a pathogen is marked for ingestion and destruction by a phagocyte) and therefore are rapidly cleared from circulation by the immune system. Additionally, the process of nonspecific protein adsorption can have a significant effect on the physicochemical properties of nanoparticles and affect their circulation, biodistribution, cellular internalization and trafficking in vivo. Traditionally, nanoparticles were made to resist nonspecific protein adsorption by surface modification with polyethylene glycol (PEG), polysaccharides, mixed charge self-assembly or zwitterionic polymers. An attractive alternative to make the nanoparticles ‘stealth’ and therefore resist fouling by proteins is to coat the nanoparticles with natural materials such as peptides, which are biocompatible, well-characterised, nonimmunogenic, biodegradable and multifunctional. While some initial studies have shown that this approach is viable and has potential to be quite useful in the various applications described above, there is still a need to develop an understanding of what is the best peptide sequence to use to coat the peptides in order to prevent nonspecific adsorption of peptides onto the coated nanoparticles and also to reduce aggregation. Therefore in this project we will utilise the de novo peptide synthesis capabilities in the Biotechnology group at NPL to construct new peptides that take inspiration from naturally occurring peptides. Then using the various high resolution surface imaging tecniques that are available within the Surface & Nanoanalysis group at NPL we will be able to characterise the films of peptides that result on the gold interfaces. Simulations will be used to provide a atomistic description of the formation of the films of peptides on the gold interfaces. Additionally, we will use simulations to study the interaction of lysozyme and fibrinogen with these peptide-capped gold interfaces to attempt to provide insight into which peptides provide the most resistence to fouling by these proteins which are commonly found in the bloodstream. Finally, we will use simulations to characterise the forces that are felt between two coated nanoparticles in order to characterise how likely they are to aggregate. Please see www.kcl.ac.uk/canes for further details of how to apply. Interested candidates should apply by 20 February if at all possible. Late applications will be considered as long as places remain, provisionally until 20 March. Informal enquiries can be addressed to the CANES Centre Manager (ca...@kcl.ac.uk).
