Skip to main content
KBS_Icon_questionmark link-ico

BiPAS Projects

Available projects - October 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)

Project Overview

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.

Biophysical Modelling of Age-related changes to Muscle Regeneration using Multiphoton and DESI-Raman Microscopy

1st Supervisor: Robert Knight (Centre for Craniofacial and Regenerative Biology)
2nd Supervisor
: Mads Bergholt (Centre for Craniofacial & Regenerative Biology)

Project Overview

Ageing affects muscle regeneration leading to weakness. Many molecular changes occur during ageing but how changes to muscle stem cell (muSC) function are related to physical properties of muscle in ageing is poorly understood. To address this important question we will combine live cell imaging with molecular characterisation of muscle to determine how molecular signatures correlate with muSC function in regenerating muscle of a living animal. Using a powerful new DESI mass spectrometry / Raman imaging microscope we will investigate how the molecular composition of regenerating muscle is altered in a zebrafish genetic model of ageing relative to muSC function.

Collagen electro-mechanics

1st Supervisor: Patrick Mesquida (Department of Physics)
2nd Supervisor
: Catherine Shanahan (School of Cardiovascular Medicine and Sciences / James Black Centre)

Project Overview

Collagen, an extracellular, structural protein forming microscopic fibrils smaller than cells, is increasingly being used in a variety of biological and medical applications for tissue-engineering. However, not much is known about the relation between the physical properties (mechanical and electrical) of single fibrils, macroscopic tissues, and the resulting cell response across different length scales. A better understanding of these interdependencies is vital for the creation of hierarchically structured scaffolds for tissue regeneration. This project will use state-of-the-art mechanical testing at the macroscale and novel methods to determine mechanics at the microscale, combined with cell cultures to gain an understanding of key biological responses.

Creating dynamic functional membrane structures; the molecular basis of biomembranes

1st Supervisor: Paula Booth (Department of Chemistry)
2nd Supervisor
: Snezhana Oliferenko (Randall Centre for Cell & Molecular Biophysics)

Project Overview

Biological systems organise themselves with efficiency and precision. We are far from a complete understanding of this natural self-assembly, which in turn limits our ability to mimic biological construction in tuneable synthetic systems. Natural membranes are formed from only two core components, proteins and lipids, but they conceal a functional sophistication that cannot be mimicked in artificial systems. We want to understand how this collective emergent behaviour of membranes arises and exploit this in artificial cells. These goals will be achieved by integrating biophysics, chemistry and synthetic biology approaches on individual molecules through supramolecular chemistry to complex biological systems.

Cryo-focused ion beam milling, cryo-electron tomography and subtomogram averaging of a large ankyrin-1 complexes from human erythrocytes

1st Supervisor: Roberto Steiner (Randall Centre for Cell & Molecular Biophysics)
2nd Supervisor
: Roland Fleck (Centre for Ultrastructural Imaging / Randall Centre for Cell & Molecular Biophysics)

Project Overview

Cryogenic electron microscopy methodologies are revolutionising structural biology. While single particle analyses typically require in vitro reconstitution of protein complexes, modern tomographic approaches allow their study in their native environment. In this project we will use the world-class facilities at King’s-CUI and expertise in cryo-electron tomography to study a large membrane ankyrin-1 complex recently discovered in human erythrocytes. We will combine cryo-focused ion beam milling and subtomogram averaging to obtain the in situ structure of the complex. Our analysis is expected to reveal ancillary subunits and possibly differences between membranes of healthy individuals and patients suffering from blood diseases.

Environment dependence of molecular cytoskeletal dynamics investigated through high speed super-resolution microscopy and tracking

1st Supervisor: Susan Cox (Randall Centre for Cell & Molecular Biophysics)
2nd Supervisor
: Maddy Parsons (Randall Centre for Cell & Molecular Biophysics)

Project Overview

The behaviour of the cell cytoskeleton is known to depend on the local environment of the cell, particularly whether it is 3D. However, the link between microscale changes in the cytoskeleton and the nanoscale dynamics of molecules in cells is poorly understood. This project will develop a novel imaging approach, where a light sheet illuminates sections of the sample and the images are time filtered and then fitted to allow tracking of large numbers of molecules in 3D at high speed in live cells. We will initially investigate the behaviour of fascin, an actin binding protein upregulated in cancer.

Integrated tools to probe chaperone-antioxidant interactions in prostate cancer

1st Supervisor: Rivka Isaacson (Department of Chemistry)
2nd Supervisor
: Ulrike Eggert (Randall Centre for Cell & Molecular Biophysics / Department of Chemistry)

Project Overview

Steroid hormone receptor (SHR) regulation plays an important role in hormone-related cancers. This project will develop an integrated chemical biology/biophysics approach to understand and exploit a tweezer-like co-chaperone called SGTA known to stabilize SHRs. The Isaacson lab has extensive experience in structurally characterizing SGTA and has recently begun working on a newly discovered SGTA-antioxidant interaction in prostate cancer. The Eggert lab has specialised cell/chemical biology expertise for elucidating the important roles membrane lipid composition play in major cellular processes. Here we join forces to examine the role of membrane lipids in SHR/co-chaperone/antioxidant interactions from single molecule, to crowded cellular context.

Novel bio-orthogonal fluorophores for advanced fluorescence polarization and polarized FRET studies of protein dynamics in biological systems

1st Supervisor: Andre Cobb (Department of Chemistry)
2nd Supervisor
: Thomas Kampourakis (Randall Centre for Cell & Molecular Biophysics)

Project Overview

The measurement of protein orientation in situ has the potential to significantly increase our understanding of their functional behaviour in real time. The use of bifunctional fluorescent probes gives us the potential to achieve this via a technique pioneered at KCL known as Fluorescence for in situ Structure (FISS). In spite of the huge potential of this highly informative biophysical endeavour, the tools to achieve this effectively are extremely limited. This studentship would seek to develop a dynamic toolkit that will be able to significantly broaden the potential targets of this biophysical technique.

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)

Project Overview

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)

Project Overview

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.

Supramolecular sensor arrays to assess and screen nanoparticle interactions in biological systems.

1st Supervisor: Andrew Surman (Department of Chemistry)
2nd Supervisor
: Khuloud Al-Jamal (Institute of Pharmaceutical Science)

Project Overview

Nanoparticles are commonly used in drug delivery and medical imaging: e.g. the use of lipid nanoparticles for delivery of therapeutic nucleic acids, like RNA vaccines, is currently growing. Such are designed carefully, and can show promise during in vitro testing, but fail – or behave unexpectedly – in vivo or in biofluids (blood, serum, nasal fluid, etc). Often this is due to unforeseen interactions like the formation of protein coronas which envelope particles which changestheir bionanointeractions. This project will use supramolecular sensor arrays –an approach more common for sensing small molecules – as a platform to assess and predict these otherwise-unforeseen interactions.

The impact of topography-induced local cytoskeletal rearrangement on metabolic cell requirements

1st Supervisor: Ciro Chiappini (Centre for Craniofacial and Regenerative Biology)
2nd Supervisor
: Andrea Serio (Centre for Craniofacial & Regenerative Biology / The Francis Crick Institute)

Project Overview

Topographical cues are widely investigated as microenvironmental stimuli for stem cells differentiation in regenerative medicine. In particular, we have recently shown that high aspect ratio nanomaterials (nanoneedles) stimulate directly multiple elements of the cell, inducing local rearrangements of endocytic vesicles, cytoskeleton, and nuclear envelope. Yet, to date there is no systematic study focusing on how these dramatic rearrangements impact the organelle shuttling and distribution across cell compartments or how organelle dynamics are carried through these strongly altered networks. In this project we will focus on the effect of cytoskeletal local pinning, wrapping and sharp bending around nanoneedles on shuttling dynamics, biogenesis and function of mitochondria in neural progenitors, neurons and astrocytes.

The nanomechanics of the endoplasmic reticulum (ER) across length- and force- scales

1st Supervisor: Sergi Garcia-Manyes (Department of Physics / Randall Centre for Cell & Molecular Biophysics / The Francis Crick Institute)
2nd Supervisor
: Ulrike Eggert (Randall Centre for Cell & Molecular Biophysics / Department of Chemistry)

Project Overview

Mechanical forces influence many aspects of cell behaviour. While much has been studied on the mechanisms governing the first stages of mechanotransduction on focal adhesions at the plasma membrane level, comparatively less is known on how forces propagate deep inside the cell. Apart from some recent inspiring work on nuclear mechanoresponse, how mechanical forces affect the different cellular organelles remains elusive. Here we will employ a combination of nanomechanical techniques with cell biology, mass spectrometry and optogenetic experiments to dissect how mechanical forces affect the endoplasmic reticulum’s function, focusing on its potential role in propagating mechanical stimuli to the nucleus.

Understanding electron transfer in Cytochrome P450 towards sustainable catalysis

1st Supervisor: Sarah Barry (Department of Chemistry)
2nd Supervisor
: Ismael Diez Perez (Department of Chemistry)

Project Overview

The drive towards sustainable synthesis of chemicals including pharmaceuticals, has led to a rise in the use of enzymes as biocatalysts in industry. Cytochrome P450 oxygenases are of growing interest as biocatalysts due to their ability to use oxygen to catalyse reactions with excellent stereoselectivity and regioselectivity. While P450s have been studied for decades due to their vital biological roles in e.g. biosynthesis of hormones and human drug metabolism, many questions remain about their biochemistry, including the control and timing of electron transfer crucial for successful catalysis. This project aims to understand the structure function relationships between protein and electron transfer towards predictable engineering  of P450s as biocatalysts.

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)

Project Overview

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.

Unravelling mechanisms of B cell activation using a physical simulator

1st Supervisor: James Millen (Department of Physics)
2nd Supervisor
: Katelyn Spillane (Department of Physics)

Project Overview

Microscopic biological systems use thermal fluctuations as fuel and employ intricate feedback mechanisms, leading to dynamics which cannot be described by standard thermodynamics. Understanding and modelling such energetics with a computer is challenging, due to the presence of widely varying time- and energy-scales. In this project you will work with a physical simulator, formed by a microparticle levitated in vacuum and controlled by electrical fields, to emulate biological processes such as B cell antigen discrimination. This project could inform the design of next-generation vaccines which are rationally engineered to elicit desired antibody responses.