Current Projects 2022
The projects listed below will be available to students commencing their programme in October 2022. Visit the BiPAS CDT page for more information on the project selection process.
Advanced fluorescence microscopy and image analysis for revealing sarcomere structure at the nanoscale
1st Supervisor: Siân Culley (Randall Centre for Cell & Molecular Biophysics)
2nd Supervisor: Mathias Gautel (Randall Centre for Cell & Molecular Biophysics)
Sarcomeres are the fundamental repeating units of striated muscle tissue. Within sarcomeres, complex molecular architecture at the nanoscale anchors long cytoskeletal actin/myosin filaments within perpendicular structures. By coupling millions of sarcomeres into myofibrils, this nanoscale organisation ultimately dictates muscle behaviour on a length scale of millimetres to centimetres. Studying the spatial organisation of the numerous protein species within the anchoring networks of sarcomeres is challenging due to the tight packing of structures beyond the resolution limit of conventional light microscopy. This project will develop and apply advanced fluorescence microscopy and analysis methods to overcome this limit and dissect sarcomere nanostructure.
Novel imaging strategies to investigate 3D tumour invasion
1st Supervisor: Simon Poland (Cancer and Pharmaceutical Sciences/Comprehensive Cancer Centre)
2nd Supervisor: Maddy Parsons (Randall Centre for Cell & Molecular Biophysics)
The key objective of this PhD studentship is to develop novel optical imaging strategies which will enable for the first time, the complete interrogation of 3D cell culture models, to understand how cancer cells to dissociate from the primary tumour, evade immune surveillance and invade surrounding tissues. The imaging platform will be based on light sheet fluorescence microscopy (LSFM) to enable high-speed volumetric imaging capability. The candidate will work closely with life scientists to develop this technology in parallel to the development of more sophisticated 3D biological models which can mimic complex cellular interactions which drive cancer progression.
Revealing the design rules of therapeutic antimicrobial and anticancer peptides
1st Supervisor: Martin Ulmschneider (Department of Chemistry)
2nd Supervisor: Paula Booth (Department of Chemistry)
Membrane-active peptides have been hailed as promising next-generation therapeutics for treating infections and cancer, due to their unique ability to bind, aggregate, and perforate membranes of target organisms with high selectivity. Selective perforation is driven by highly dynamic processes spanning a wide range of temporal and spatial scales that are poorly understood. This project will apply both experimental techniques and atomic detail simulations to reveal the molecular mechanisms underpinning selectivity. The ultimate goal is to derive rules for the design and optimization of peptide therapeutics targeting bacteria, fungi, envelope viruses, and cancer cells.
Understanding muscle tissue formation and the origins of muscle defects by combining agent-based modelling and embryological data of muscle development
1st Supervisor: Katie Bentley (Department of Informatics)
2nd Supervisor: Malcolm Logan (Randall Centre for Cell & Molecular Biophysics)
Muscles develop with high fidelity to achieve their correct size, shape and position within the musculoskeletal system. During muscle tissue formation, muscle fibres undergo a sequential process of orientation and compaction to form discrete bundles, which in some instances can be followed by splitting of a single bundle to produce two daughter muscles.Using a combination of experimental data and agent-based modelling tools we will generate predictive models of muscle fibre organisation and tissue morphogenesis, modelling the step-by-step processes that developing muscles undergo. These tools can improve understanding of tissue morphogenesis and how disruption of these process leads to disease.