PhD and Employment Opportunities

This project aims to optimise sorting of biological cells according to their mechanical properties by utilising novel microfluidic devices.

Various diseases lead to alteration in the physical properties of the cell plasma membrane such as membrane elasticity, viscosity and electrostatics. This could compromise biological functions hosted by the plasma membrane.  Sorting of cells according to their physical properties is therefore an important step in understanding the effects of disease on membrane properties and cell function. This project will explore novel strategies for cell sorting based on their viscoelastic properties, using structured microfluidic devices with carefully controlled geometries. The concept will be validated on subpopulations of human red blood cells with different viscoelastic properties (membrane bending and shear moduli, membrane and cytoplasmic viscosity) and geometry (volume-to-area ration), all of which are important for cell deformability. Later stages of the project will focus on designing and implementing adaptive microfluidic devices capable of optimising cell sorting depending on particular cell properties in the subpopulations. This is an exciting interdisciplinary project suitable for a student interested to work on the boundary between physics and biology.

• Please contact Dr Peter Petrov or Dr Stefano Pagliara for more information

Recently it has become possible to design and make intricate 3D synthetic nanostructures. This is the basis of a revolution in material science as well as new drug designs and delivery methods to mention just a few applications. In this project we will design and make intricate 3D nanostructures from DNA that we design on the computer and assemble in the laboratory, so called DNA origami.

A major challenge has been the characterisation of such purpose designed structures to ensure that they are indeed folded in 3D as designed on the computer. Here we will use new optical imaging techniques, so called optical super-resolution, to directly take molecular scale images of the 3D DNA origami structures with a resolution that is better than 10 nm. This will also allow us to probe the flexibility of these structures when we mechanically load them.

An important aspect of the imaging of these nanostructures will be the use of deep learning methods to analyse the image data and help us construct even higher resolution images of these synthetic nanostructures. We will implement a number of deep learning approaches that have recently been introduced and train them with our data to provide analysis with previously unattainable spatial and temporal resolution.

The insights of the 3D DNA origami design and synthesis will be used to implement and validate molecular scale biological imaging applications that, for example, can monitor at the molecular scale how a virus enters a cell.  The student will receive training in advanced super-resolution microscopy, DNA nanotechnology, deep learning and application of DNA structures for biological imaging.

• Please contact Prof Christian Soeller or Dr Alex Corbett for more information

Biography: I am an Associate Professor in Biomedical Spectroscopy at the School of Physics and Astronomy, University of Exeter. My research is focused on the development of Brillouin, Raman and FTIR spectroscopy and imaging methods for applications in life sciences and healthcare. I am particularly interested in the physical and chemical aspects of biological systems on a microscopic scale, as well as their implications in tissue function and pathology. Previously I developed the application of attenuated total reflection (ATR) FTIR spectroscopic imaging to atherosclerosis in animal models of the disease. I also applied ultrafast time-resolved optical Kerr effect (OKE) and complementary THz Raman spectroscopy to elucidate the dynamics, structure and interactions in ionic solutions. My PhD project was focused on investigating the hydrogen-bonding properties of isomeric octanols from liquid to supercritical fluid conditions using FTIR (mid and near infrared), Raman and depolarised Rayleigh scattering. I currently co-chair the EU COST Network BioBrillouin aimed to advance the development and applications of Brillouin spectroscopy in biomedical sciences. I am also co-investigator in the EPSRC Programme Grant “RaNT” which will develop novel nanotheranostics for translation of Raman spectroscopy to the clinics.

Please contact Prof Francesca Palombo

Phagocytosis is the fascinating process by which immune cells in our body search out, engulf and destroy foreign particles like bacteria. Almost all previous work in this area has only studied phagocytosis of spherical beads. This is despite real cells having to engulf a whole host of different target shapes including capped-cylinders (such as bacteria like E. coli), hourglasses (such as budding yeast during division) and tubes (such as asbestos fibres).

In this project, you will investigate how target shape and size affect phagocytosis, including which shapes can be engulfed and how long it takes. This will involve making particles of various interesting shapes, assaying how phagocytosis depends on particle shape and size using a new dual-micropipette system, and developing tools to automatically extract the success rate of phagocytosis.

This PhD will be based in purpose-built labs in the recently-opened Living Systems Institute. It will involve a combination of wet-lab experiments, microscopy, cell culture, and phagocytosis assays. It will also involve some image analysis using ImageJ and/or MATLAB. This will train you in an excellent combination of skills that will be valuable in your future career, be it within or outside academia

• Please contact Dr David Richards, Dr Kirsty Wan or Dr Charlie Jeynes for more information

Neuroblastoma is a pediatric solid tumor of the sympathetic nervous system with an unmet need of novel treatment approaches. In-vitro cultured cancer cells can serve as important models for preclinical testing of anti-cancer compounds. 3D cell culture formats have emerged as powerful paradigms that can closely mimic in-vivo culture conditions. However, finding optimal conditions that allow the retention of original tumor features during in vitro 3D culturing of cancer cells is challenging. This research project builds upon a novel high-throughput imaging tool developed in FG lab which allows for the fast imaging and on-demand selection of flowing microdroplets using machine learning approaches. We will use imaging information for neural network training that will be used for selection of the best spheroids. The selected cultures will be subjected to differentiation with signalling molecules, before analysis for gene expression (via immunostaining) and/or high-content screening. This project will pave the way towards building neuroblastoma tumour development models for use in differentiation therapies.

• Please contact Dr Fabriece Gielen or Prof Christian Soeller or Dr. Akshay Bhinge for more information

The ability to generate ultra-short pulses of light has revolutionised biological imaging. Compressing energy delivery into femto-second timescales has enabled super-resolution optical imaging down to nanometric levels, and non-linear imaging capable of reporting the chemical composition of living systems in-situ. These techniques teach us how biological systems function and crucially, how they fail.

When an ultra-short optical pulse enters living tissue, it fragments and spreads out in both space and time. This scattering disrupts the formation of images deeper than a few hundred microns from the surface. Recently, the field of wavefront shaping has emerged as a powerful method to overcome some of these scattering effects. By 'pre-scrambling’ the light in just the right way before it enters the tissue, imaging can be achieved deep inside scattering systems. However, controlling light in both space and time, critical for ultra-short pulse delivery, is still an open challenge.

The aim of this project is to develop new technologies to control ultra-short optical pulses inside scattering systems, with the ultimate goal of imaging deeper inside living tissue. This builds on the wavefront shaping and non-linear optics experience in the Phillips and Winlove labs.

• Please contact Dr David Phillips or Dr Ben Sherlock or Prof Peter Winlove for more information

Migratory songbirds have a remarkable “sixth sense” that allows them to use the Earth’s magnetic field as a source of navigational information. This molecular compass is hypothesized to rely on coherent spin dynamics in radical pairs, which are formed in the protein cryptochrome, located inside the animals’ eyes (Annu. Rev. Biophys. 45 (2016) 299). This remarkable, yet compelling, supposition relies on long-lived quantum coherences and entanglement, i.e. traits that are not typically associated with the wet, warm and noisy environment characteristic of living organisms. The hypothesis of a direct quantum underpinning of biological processes raises fundamental questions about our understanding of life and offers the prospect of learning from nature how to exploit quantum phenomena in noisy environments in ways that could surpass current technologies.

We support projects to investigate the mysteries of cryptochrome magnetoreception and related phenomena of biological magnetosensitivity by theoretical means (i.e. spin dynamic calculations based on the theory of open quantum systems). The current research focus is on the recently discovered effects related to the quantum correlation of three radicals (the so-called chemical Zeno effect), effects emerging in driven open quantum systems and the development of new modelling tools allowing for a hybrid quantum-semiclassical description of the dynamics of larger spin systems. Collaborative experimental studies are also possible (e.g. using time-resolved HDX-mass spectrometry to investigate cryptochrome in vitro). Projects will be adapted to your particular interests, prior knowledge and background.

• Please contact Dr Daniel Kattnig or Dr Jonathan Phillips for more information

Techniques such as X-ray crystallography and electron cryo-microscopy give us extraordinary insights into the structure of the components of life – with one caveat: the structures are static and cannot tell us directly about their dynamics and function. All-atom molecular dynamics simulations can be used to shed light on this, but are restricted to small proteins or protein complexes and very short time scales. However, their results can be used to build models with fewer degrees of freedom. This approach is called coarse-graining and allows one to simulate and study large protein complexes on biologically relevant time scales.

We propose to use this bottom-up coarse-graining approach to study the mechanisms of a variety of biological systems, for example molecular motors that function in microbial motility or the movement and adsorption of viruses in a dense population of bacteria.

• Please contact Dr Wolfram Moebius or Dr Daniel Kattnig for more information

Longitudinal growth of the bones in the human spine occurs at their interface with the intervertebral discs. This interface, called the endplate, comprises a layer of cartilage and bone and acts as the primary site of growth through propagation and calcification of the cartilage. A key component for healthy growth is the vast capillary network in the underlying bone. These capillaries supply nutrients, signals and materials required for growth to occur. We know little about this capillary network and a better understanding will provide a baseline for elucidating the mechanisms of abnormal growth such as seen in spinal deformity. The proposed project will address this knowledge gap by characterising the structure and function of the capillary network in a bovine model. The structure will be visualised, mapped and characterised using a range of novel microscopy and image analysis methods. The function will be assessed using a combination of imaging and perfusion experiments to determine fluid and solute transfer to and through the surrounding tissues. The effects of a mechanical load will also be evaluated.

• Please contact Dr Jude Meakin or Dr Junning Chen for more information

As part of the leading Biospec unit based within Biophysics at the University of Exeter, you will have access to world leaders in applying Biophotonics solutions for healthcare needs. With our partner hospitals (Royal Devon and Exeter and Gloucestershire Hospitals) we seek to solve clinical needs with physical science based solutions.

We have currently projects working across:

Bio fluid spectroscopy and novel methods and instrumentation to provide molecular analysis of liquid biopsy samples for clinical diagnosis and monitoring of disease.

Nanomedicine combining nano constructs and photonics to provide both read out / detection / thermal therapeutics. We lead the EPSRC healthcare technologies Raman Nanotheranostics RaNT programme that explores novel nanotechnologies coupled to light for detection and monitoring of disease as well as triggering specific treatments. We have two funded studentships as part of this programme of work.

We host a EPSRC national user facility for coherent Raman imaging for biomedical samples - CONTRAST

• Please contact Prof Nick Stone for more information

This EPSRC-PhD project will develop single coronavirus sensing capabilities based on the laser interferometric technology pioneered in Professor Vollmer's laboratory, see Vollmerlab.com, and apply the instrument for testing saliva and nasal patient samples for CoV2 virus nanoparticles.  The goal is to develop new sensing physics for the specific single CoV2 virus detection by laser-interferometers (optical microcavities). The optical method has already been successful for the detection of Influenza A and the clinical trial is to confirm appropriate high-throughput sensing to detect the virus CoV2.

This project is a collaboration between the University of Exeter (Micro-Laser Interferometry, sensing physics); University of Plymouth (Adeno- and coronavirus surrogates for initial testing, receptor molecules); NHS Taunton (deployment and test of instrument with patient samples).

The project will involve: 1) new instrumentation physics for building a micro-interferometer based on whispering-gallery modes excited in glass microspheres see Optical Whispering Gallery Modes for Biosensing - From Physical Principles to Applications 2) miniaturisation by integration with micro/nanofabricated photonics structures and 3D printing, advanced microfluidics 3) Application of optoplasmonic signal enhancements for ultra-sensitive detection at the single virus particle and possibly single molecule level 4) application of advanced sensing schemes based on exceptional points and PT symmetry.

• Please contact Prof Frank Vollmer for more information

Toxins secreted by bacteria are major causes of disease. Usually, the interaction between the toxin and the cell plasma membrane is a complex, multistage process, which may ultimately lead to cell death. Whilst the biochemistry, molecular and cell biology of this process has been extensively studied, little is known about the role of the membrane physical properties in cell susceptibility to toxins. We have pioneered research revealing that electrical and mechanical properties of the cell plasma membrane could determine cell susceptibility to toxin. Membrane physical properties are also altered in disease, thereby influencing cellular susceptibility to toxin. This project will focus specifically on a class of toxins called pore-forming toxins. We shall investigate how membrane physical properties (viscoelasticity, electrical properties and their changes in disease) affect the three stages of toxin-membrane interactions (binding, aggregation and membrane insertion) leading to formation of pores in the membrane and, ultimately, cell lysis. We shall also investigate the effects of elevated oxidative stress, an ubiquitous condition in a number of diseases. This will be achieved through integrated cross-disciplinary approaches accounting for each aspect of toxin-membrane interactions and their interdependence.

This research will have an impact on the growing community of scientists working on the mechanisms of invasion of host cells by bacterial pathogens. It will inform the development of novel therapeutic approaches to combat bacterial infections in humans and domestic animals, major concerns for human health and for farming communities.

This is an exciting interdisciplinary project suitable for a student motivated to work at the boundary between physics and biology..

• Please contact Dr Peter Petrov for more information