Summer Studentships

My research group aims to discover how to modulate the immune system for improved prevention and treatment of lung diseases. My current research focus is on the lymphatic vessels that make vital contributions to fluid balance and immune responses inside our lungs. We currently lack approaches to selectively enhance or inhibit pulmonary lymphatic function, partly because it is challenging to image pulmonary lymphatics. My group are therefore developing new approaches to shrink and grow the pulmonary lymphatic vasculature, and new imaging methods to image and measure these structures in 3D. Students will learn techniques for staining and clearing tissues for 3D imaging, will receive training in confocal microscopy and will develop skills in image analysis. The long-term goal of this work is to develop new medicines that can accelerate the healing of injured lungs and prevent the spread of lung-metastatic cancers.

Hydra are simple aquatic animals of ancient evolutionary origin. As model organisms they are used for studying fundamental processes that underlie biological phenomena including regeneration, stem cells and neural networks. Hydra tentacles contain specialised mechanosensitive cells (nematocytes) which detect and respond to mechanical signals. These cells are involved in hunting, defence and locomotion. We are studying hydra to understand how structures in these cells support their function, and what they can tell us about mechanosensitive structures in sensory organs like the ear. To do this we are using a variety of electron and light microscopy methods.

This project will focus on a novel observation in our data, an interaction between an uncharacterised granule and a porosome-like structure in the plasma membrane. Porosomes are cage-like structures that allow ‘kiss-and-run’ partial secretion of granule contents, a vital process in nerve function and hormone and enzyme secretion. Their existence is still somewhat contentious. Our observations are different to those described in other systems (airway epithelium, synaptic junctions) and are the first time they have been observed in a non-mammal.
The project student will be expected to undertake light (expansion microscopy) and electron microscopy (including 3D volume electron microscopy) on hydra to investigate this putative granule/porosome interaction. They will also learn microscopy image analysis. The project will be co-supervised by the Imaging Unit Manager at the UCL Institute of Ophthalmology and Microscopy Unit Manager/Senior Research Fellow at the UCL Ear Institute

AI-directed imaging workflows hold promise to revolutionise data collection on high-resolution confocal and other imaging systems. Likewise, multiscale imaging of whole organisms could unlock key holistic context for high-mag and super resolution functional imaging of dynamic processes and will inform and elevate connectome and systems biology research. This project will focus on developing an AI-driven automated workflow for multi-organism, multiscale, imaging of live functional neurobiological, cardiovascular, and metabolic systems on a state-of-the-art, dedicated, purpose-built, whole-organism superresolution imaging platform.

The student will be taught the fundamentals of light microscopy imaging including confocal, multiphoton, and superresolution. They will learn how to train multiple levels of AI models to detect biological features in live whole zebrafish. A number of projects in the imaging facility will require custom AI-driven workflows and one will be assigned that interests the student. The microscope software platform will allow them to train AI-models and generate a fully automated image acquisition protocol that images, at high throughput, a population of whole live zebrafish: From whole-fish overview down to AI-directed target ROIs imaged with multichannel super resolution structural imaging and/or fast functional dynamic imaging across time. If time permits, they may also have the opportunity to introduce a level of AI-directed optomanipulation to detected target cells.

Salmonella enterica serovar Typhimurium (STm) is a significant human enteric pathogen capable of invading both macrophages and non-phagocytic cells such as epithelial cells. It secretes various factors to manipulate host processes and evade immune responses. Disruption of Ca²⁺ signalling is a strategy used by many microbes, including viruses and bacteria, to dampen inflammation and establish their replicative niche. Enterobacteriaceae like Klebsiella and Shigella have been shown to modulate host Ca²⁺ signalling to influence infection dynamics and pathogen survival. However, the impact of intracellular Ca²⁺ flux on Salmonella survival and the role of its virulence factors in counteracting this host response remain unclear.

This project aims to answer two questions:

1. Do host cells modulate intracellular Ca²⁺ flux to combat intracellular Salmonella?
2. What virulence factors might Salmonella deploy to combat host Ca2+ signalling?

This project will utilise tissue culture and infection of in vitro cell lines, including human macrophage-like THP1 cells and A549 epithelial cells. Cells will be treated with various pharmacological agents to manipulate Ca²⁺ levels such as BAPTA-AM, ATP, thapsigargin and Ca2+ ionophores. The impact on intracellular survival of STm will be assessed using gentamicin protection assays. Additionally, Salmonella type 3 secretion system effectors will be screened for their capacity to inhibit Ca2+ signalling via luminescence and immunofluorescence assays using THP-1 dual reporter cells.

The student will be expected to engage with the project and lab members, attend lab meetings and take part in journal clubs. Additionally, a closing presentation is expected to discuss project findings to date.

Short spells of hot dry air can cause fast desiccation of crop land, devastating crop yields. These ‘flash droughts’ are becoming more prevalent as the climate crisis worsens. This project will examine how the model plant, Arabidopsis, changes its canopy to cope with this kind of low humidity.

At low humidity, plants produce smaller leaves with fewer stomata (pores) to prevent water loss, helping the plant survive. This project will try to answer whether this reduction in leaf growth is due to hydraulic constraints on photosynthesis (closing stomata prevents CO2 uptake) or changes in growth regulating hormones such as abscisic acid, gibberellin, auxin and ethylene. 

You will work closely with Dr Jim Rowe, an expert in plant stress biology, molecular biology, imaging and image analysis and to learn modern research techniques, experimental design and data analysis methods. You will also be welcome to join and contribute to lab meetings to get a wider understanding of the science.

In this project, you will use the following techniques:

• Cutting edge microscopy (confocal and FRET) to image biosensors to detect hormone and sugar concentrations
• Raspberry pi cameras to track leaf growth over time in a variety of mutants
• Stomatal impressions and microscopy to count stomata
• Image analysis to measure stomatal number, leaf size and hormone concentrations

Spider webs are marvels of natural engineering, exhibiting exceptional structural diversity and functionality. This project aims to explore the micro- and nanoscale architecture of different spider web types using advanced scanning electron microscopy (SEM). Additionally, it will investigate the interaction of spider silk with environmental factors such as humidity, offering insights into their unique material properties.

The research will involve imaging various spider web samples, optimising sample preparation methods for SEM, and employing Environmental SEM (ESEM) to study silk behaviour under atmospheric humidity. Single-fibre tensile testing will also be trialled to assess the mechanical strength of spider silk at the microscale under controlled environmental conditions.

Student Responsibilities:

• Complete training in SEM operation, sample preparation, and advanced SEM techniques
• Conduct a literature review on spider web imaging and the use of electron microscopy in silk studies
• Perform detailed imaging of spider web structures and analyse differences at micro- and nanoscale levels
• Utilise in-situ ESEM to investigate the impact of humidity on silk properties
• Trial single-fibre tensile testing to understand the strength and elasticity of spider silk under varying humidity conditions
• Present findings through an engaging scientific poster and a concise oral presentation (~15 minutes)

Advanced paternal age is associated with an increased risk of fathering children with genetic disorders. The Goriely lab at the MRC WIMM in Oxford characterises the mechanisms that drive this ‘paternal age effect’, having discovered a new process termed ‘Selfish Selection’ that takes place in the testes of all men as they age. We have previously shown that when new ‘selfish’ DNA mutations occur in human testes, they form small clusters of mutant stem cells, which spread over time in a manner similar to tumours. This explains how selfish mutations become more abundant in sperm as men age - and why older fathers are more likely to have children with specific genetic disorders. Using mice models carrying known disease-causing ‘selfish’ mutations, we assess their long-term impact on male fertility. Our preliminary results suggest that, although selfish mutations cause serious diseases in children, they also increase male fertility.

This summer studentship project aims to investigate the impact of selfish mutations in novel genes and assess how they affect male fertility in mouse models. The project will be carried out both in the Goriely Lab who have extensive experience of laboratory research and in the WIMM Imaging Centre offering access to state-of-the-art microscopy training. The student will learn to dissect mouse testis samples, perform protein staining, analyse specimens with widefield and confocal fluorescence microscopy, quantify stem cell number and perform statistical analysis. The student will be embedded into the wider Institute’s research landscape and participate in lab meetings, seminars and lectures.

Colloidal quantum dots (QDs) show great promise for bioimaging and sensing applications due to their high photoluminescence quantum yields and easily functionalised surfaces. These properties can be enhanced when the QDs are used as building blocks to form mesoscopic supraparticles (SPs). Formed solely from QDs, the SPs can range from a few hundred nanometres to several microns in size. Due to the high refractive index of the QDs that make up the SPs, the SPs act as optical antennas or micro resonators, enhancing light absorption and emission when compared to singular QDs. These SPs have even shown laser oscillation due to the presence of whispering gallery modes which in turn allow the possibility of refractive index sensing. Current research focusses on highly toxic cadmium based QDs, however for biological applications, a non-toxic alternative is needed. 

During this project, the student will synthesise non-toxic, water soluble, AgInS2 QDs using an eco-friendly low temperature method. A phase transfer will then be performed resulting in QDs soluble in solvents such as chloroform and toluene. SPs will then be synthesised using the QDs as building blocks in an oil-in-water emulsion template technique. Finally, the SPs will be functionalised with biomolecules to test the practicality of the material for biosensing applications. All the materials will be characterised via zeta potential, FTIR, SEM, absorption and photoluminescence spectroscopy. This project is highly multi-disciplinary, combining the theory of quantum dot physics with chemical experimental techniques for biological applications.

Intrinsically disordered regions (IDRs) of proteins are inherently dynamic and lack a defined tertiary structure. IDRs often function as flexible sequences that link binding motifs in proteins, therefore their length, dynamics and ensemble properties can modulate molecular recognition. Consequently, it is important to consider linker properties when designing synthetic proteins with multivalent binding properties. Typically, naturally occurring sequences or glycine-serine repeats are used as linkers in protein engineering projects. However, neither approach is ideal; the physicochemical and ensemble properties of a naturally occurring linker sequence may not match the use case, while it can be challenging to synthesise DNA encoding highly repetitive sequences.

The aim of this project is to test an in-house computational tool for designing bespoke linker regions that (a) have sequences that are easy to synthesise; and (b) display ensemble properties that are tailored for multivalent binding to a target protein. The project will comprise both computational protein design and experimental characterisation, and would suit someone with good familiarity with Python and structural biology.

The initial portion of this 6-week project would use our recently developed tools to design synthetic linker sequences with different lengths and sequences and then computationally evaluate their properties in the context of a multivalent binding protein. We would then experimentally test 5 designs, evaluating expression level, stability and binding properties. The practical part of the project would expose the student to bacterial cell culture, protein expression and purification and biophysical characterisation of protein stability and binding.

Dense surface-associated colonies of bacteria known as biofilms are the cause of nearly half of all healthcare-associated infections. Biofilms have been shown to promote antibiotic resistance; therefore infections in implanted medical devices such as catheters and intravenous lines are extremely difficult to treat clinically.  The prevention of biofilm formation requires understanding how bacteria can adhere to surfaces and proliferate. Mathematical models are able to exploring biofilm formation and prevention methods virtually.  In this research project the student will learn and explore stochastic mathematical descriptions of individual bacteria dynamics, implement an agent-based computational model and use this model to predict the efficacy of biofilm mitigation measures such as surface chemistry or roughness variations. This will help the student develop mathematical modelling skills and scientific computing skills.

Diamond Light Source is the UK’s national synchrotron, where we use X-rays to study various materials, including biological cell representatives from across all kingdoms of life. To gain comprehensive information about the system we regularly need to employ different techniques with the same sample. This often involves transitioning samples between different beamlines of the synchrotron. However, transferring biological samples between different instruments poses a significant challenge, as we must consider the sample requirements and the conditions needed for each technique.

In this project, we will explore how various sample preparation methods influence correlative X-ray imaging of cells treated with iron (Fe) nanoparticles, which will act as a proxy for similar drug-like molecules. We will focus on the correlative workflow between two of Diamond’s beamlines: cryo-soft X-ray tomography (beamline B24) and the hard X-ray nanoprobe (I14). We aim to investigate how sample preparation at both cryogenic and room temperature impacts each technique, and how to minimise disruptions to the morphology or chemistry of the cells.

This will create a reference database for researchers looking for valuable insights into the elemental, chemical, and biological composition of cells.

This project provides the opportunity to work in a world-class synchrotron, developing skills for sample preparation using two advanced and in-demand techniques in a BSL-2 lab.  We are seeking a student interested in interdisciplinary science, combining biology and chemistry to tackle practical challenges in microscopy. This work requires attention to detail, a passion for learning, laboratory experience in biology/chemistry and a keen interest in imaging.

When a microscope acquires an image, it will always be blurred due to the limitations of the physical optics of the system. Deconvolution is a computational technique to correct for this blurring. Deconvolution allows biology researchers to push the limits of their microscopes, see the smallest details possible and potentially reveal previously unseen components of life! In this project you will work within a microscopy facility to develop user friendly work streams for users to digitally improve the image quality. This will involve collecting images using microscopes to calculate the amount of blurring caused by the system; investigating existing tools for their ease of use and quality of results; and writing guides for other users to follow. The project will focus on two types of microscopes, a point scanning confocal and a lattice lightsheet, managed by the Computing and Advance Microscopy Development Unit (CAMDU) at Warwick. Under supervision of CAMDU's imaging specialist, you will learn how to use these systems to record your own images of reference and biological samples. Then, working with CAMDU's computing specialist, you will use these images to test and compare existing software tools. The final stage of the project will be to select the best tool and implement a deconvolution workflow that can be followed by other users of these microscopes.  This project would suit someone with an interest in biological research with microscopy or computing. Some programming experience (any language) and A-level maths or equivalent would be helpful but not necessary.

The migratory capacity of metastatic cancer cells is associated with the acquisition of features within the spectrum of the epithelial-to-mesenchymal transition (EMT) phenotype. Development of EMT involves the increased expression and assembly of the intermediate filament vimentin accompanied by the polymerisation of F-actin into branched filaments, which fuels the formation of cell protrusions at the leading edge of migrating cells. This process is regulated by the multimeric actin nucleation factor Arp2/3 complex, which is activated by the WASP/WAVE family of proteins. 

Our published in silico work (currently validated in vitro) has uncovered the co-transcription of the genes coding for vimentin, WASP (the family member of the WASP/WAVE proteins that in normal physiological conditions is exclusively expressed in haematopoietic cells) and specific components of the Arp2/3 complex in various epithelial tumours. No changes in the ubiquitously-expressed WASP homologue (N-WASP) was associated with the expression of the EMT signature. 

Using the WASP KD breast cancer cell lines that we have generated, the summer student will explore the possible role of WASP in regulating the unit isoform composition and localisation of the Arp2/3 complex in cells undergoing EMT. For this purpose, the student will be trained in cell culture, microscopy and analysis of fixed and live specimens as well as in detection of proteins by Western blot and will compare the following parameters in parental vs WASP KD cells: 1) Vimentin and F-actin organisation; 2) Levels of expression and distribution of the Arp2/3 components; and 3) migratory capacity (random and chemotactic migration).

Biofilms are made up of a complex soup of extra-cellular DNA, proteins and polysaccharides that surround bacterial colonies and play a key role in persistent infections and bacterial resistance to antibiotics by reducing the dosage of antibiotics reaching the pathogens. In doing so they further exacerbate the problem of rising antibiotic resistance within pathogenic bacteria. As such it is key that we understand the fundamental physical and biochemical properties of biofilms and how their constituent components affect these properties. The understanding of these properties will allow for the better targeting of persistent infections through combined therapies targeting not just the bacteria but the biofilms themselves.

The project aims to build model biofilm using a DNA hydrogel and DNA binding proteins, that will allow for the probing of the physical properties of a biofilm, while forming the basis for further work engineering a more complex model system.

In this project a student will benefit from biochemical and molecular biology training in working with and assaying proteins as well as constructing DNA hydrogels. The student will also use sub-millisecond super-resolved fluorescence imaging to track diffusion through the model biofilms to assess how changes in biofilm makeup or changes to chemical conditions such as ionicity or pH affect the physical properties of model biofilms. They will also use confocal FRET microscopy to assay the effects of changing chemical conditions on the individual bridging or bending actions of DNA binding proteins on fluorescently labelled DNA molecules.

Cells are complex, highly organised structures, with the cytoplasm subdivided into compartments allowing spatiotemporal separation of a huge number of different molecules for tight control of biochemical reactions. A number of these compartments lack an enclosing membrane, collectively known as condensates or “membraneless” organelles, with liquid-liquid phase separation (LLPS) established as a key phenomenon driving their formation.

Optical microscopy has revealed the importance of these organelles in diverse cellular processes. Condensates can adopt a variety of material states but the relationship between the material state and biological function remains an open question. Bacterial aggresomes, LLPS-driven structures, concentrate vital mRNA and proteins, aiding survival under stress. This project aims to investigate the viscoelastic properties of bacterial aggresomes using biophysical tools like super-resolution microscopy and optical tweezers. The student will develop tools to explore either:

• Implementing a dual optical trap to our existing optical tweezer setup using an acousto-optical modulator (AOM) and the programming of control software on an FPGA using LabView. This instrument will then be used to characterise the material state of the aggresome.  
• Implementing 3D single-particle tracking capabilities using point spread function engineering with a spatial light modulator. This technique will be used to probe, in three dimensions, the spatial dependence of the aggresome’s material state from the diffusivity fluorescently-tagged aggresome proteins.

The student will work in the highly interdisciplinary Physics of Life group at the University York at the forefront of biophysics research, developing key skills for a career in research. 

Differential phase contrast (DPC) microscopy is a method of quantitative phase imaging which facilitates high-resolution live imaging of biological specimens. DPC affords high optical sectioning power, allowing selective visualisation of thin planes within thick 3D specimens, and performs well with highly absorbative dyes, such as the amyloid-binding dye Congo Red. We have built a DPC system that couples to the Mesolens, a cross-scale imaging platform with a capture volume of 108 mm³ and sub-cellular spatial resolution (700 nm lateral, 7 μm axial). The combination of DPC with the Mesolens presents timely opportunities to apply quantitative phase imaging to complex, 3D, live specimens across spatial scales. We used the Mesolens to discover intricate networks of nutrient transport channels in mature E. coli biofilms. These bacterial communities are a strategic priority for industrial biofouling, food security and the clinic – allowing bacteria to become over 1000x more resistant to antibiotics than their free-swimming counterparts. Our research focuses on the use advanced multi-modal imaging methods to study the formation and exploitation of biofilm transport channels as a new route for antibiotic delivery. We aim to use mesoscopic DPC (mesoDPC) to quantify the channel matrix, the main structural component of the channel network and presents a physical barrier antibiotics during treatment. We will use mesoDPC to image biofilms stained with the amyloid-binding dye, Congo Red, which will reveal the matrix distribution in the biofilm channels. We will quantify the distribution across spatial scales before and after antibiotic treatment to determine the interplay between biofilm matrix and successful antimicrobial delivery. This project will see the first use of DPC to study biofilm architecture, presenting a great opportunity for future research applying multi-modal quantitative phase imaging to microbiology.