DTP3 Cohort 5 Details
Matthew Kirby
University of Liverpool
Supervisor: Dr Emmanuel Biau
Project title: Brain rhythms that serve as the ‘binder’ for memory and concept formation
Using EEG and behavioural data, we will examine the effect of synchronicity and variation between visual and auditory cues and how that relates to memory encoding. This line of enquiry will delineate neurological activity - in terms of brainwaves and localization - involved in memorization and recall.
Julia Pryde
Durham University
Supervisor: Prof Francesco Boselli
Project title: Development and Engineering of Ciliated Tissues: Unravelling the Role of Mechanical Forces with Smart Tissue Scaffolding
The epithelial tissue within the lungs is covered with thousands of hair-like structures called cilia. Their coordinated beating generates extracellular flow through the airway, clearing mucus and germs from the respiratory system. Dysfunction of these ciliated tissues can result in life-limiting diseases such as primary ciliary dyskinesia and cystic fibrosis. The spatial organization of the cilia is essential for coordinating their collective function and establishing long-range transport. Mechanical forces are emerging as important players in the development of these tissues, but the underlying cellular mechanisms remain elusive. Studies have demonstrated poor alignment and reduced transport efficiency in cells grown without the in vivo mechanical environment. However, when exogenous fluid flow is applied, cilia can realign to follow the direction of flow, thus enhancing the efficiency of fluid transport. Moreover, mechanical forces have been shown to regulate cell size, cilia number, and cell division. We aim to determine the interplay between the forces arising from the interactions of cilia with the extracellular fluid and the internal mechanical state of the cells, as well as their contribution to the self-organization of the tissue. We will quantify cellular shape and dynamics using live imaging and techniques such as traction microscopy within a controlled biomechanical microenvironment. The impact of mechanical forces on cell shape and tissue remodelling will be explained through modelling and validated by perturbing the mechanical environment and interfering with relevant mechanogenetic players. Part of this effort involves developing a novel cell substrate based on magnetic nanoparticles, which will allow precise control and perturbation of mechanical forces in space and time in response to an applied magnetic field. By combining developmental biology, material sciences, fluid mechanics, and tissue mechanics, we propose a novel approach to understanding the complexity of how mechanical forces impact tissue form and function.
Beñat Yañez
Durham University
Supervisor: Prof Alistair McGregor
Project title: Eye development, structure and vision in the pest species Drosophila suzukii
Drosophila suzukii is an invasive fruit fly which has become a problematic agricultural pest. It develops a spectrum of phenotypic variation depending on environmental conditions. For example, at low temperatures and short days in autumn and winter these flies develop more pigmentation and have larger wings than at higher temperatures and longer days in spring and summer. Of interest to my project is their eyes. The ‘winter' morph has more but narrower ommatidia than the ‘summer' morph, which might lead to differences in their visual capabilities including acuity and contrast sensitivity. In this project, in Professor McGregor’s lab, I will characterize the differences in eye morphology between these two morphs, investigate the developmental basis behind these differences and test the impacts of these differences on vision. For this, I will use various imaging technologies including X-ray synchrotron tomography with Dr Kittelmann at Oxford Brookes. I will also generate RNA-Seq datasets to identify differentially expressed genes from the developing eyes under different environmental conditions and then test their role in regulating differences in eye morphology. Finally, under Dr Nityananda at Newcastle University, I will experimentally assay fly behaviour to determine whether the two morphs differ in their visual abilities. These findings could help understand the seasonal behaviours of these flies and inform tactics to combat this pest species.
Aminat Adeola Adesina
Newcastle University
Supervisor: Dr David George
Project title: Micromoth: Unraveling the roles of microbes in the ecological success of two invasive moths
The tomato leafminer (Tuta absoluta) and the diamondback moth (Plutella xylostella) are devastating invasive lepidopteran pests that affect vegetable crops, including tomatoes, cabbage, potatoes, cauliflower, and broccoli. The tomato leafminer and diamondback moth cause extensive harm to host plants, resulting in substantial yield loss and a huge economic impact. Microbial symbionts contribute significantly to shaping the invasive success, persistence, and resilience of these moths. Microbes enhance the fitness of tomato leafminer and diamondback moth by detoxifying plant defense chemicals, facilitating adaptation to a specific nutritional niche, and degrading pesticides, thereby conferring resistance. This microbial support not only enhances the herbivorous lifestyle of the pests, but also complicates their management, making conventional insecticidal control methods progressively ineffectual, and potentially impacting long-term efficacy of emerging approaches (eg biopesticides). A deeper understanding of the influence of microbial partners in the adaptability, resilience, and ecological success of the tomato leafminer and diamondback moth is therefore essential. Furthermore, targeting the moths’ microbial partners offers a potential route to provide a novel and environmentally friendly sustainable strategy for the management of these lepidopteran pests. The project will investigate the role of microbial communities throughout the developmental phases of tomato leafminer and diamondback moth, emphasizing the contributions of the microbial partners to the ecological success of tomato leafminer and diamondback moth.
Lucie Marx
University of Liverpool
Supervisor: Dr Bettina Wilm
Project title: Analysing the molecular and cellular mechanisms involved in tissue homeostasis and scar formation in the peritoneum using novel photo-activated photosensitisers
The peritoneum is a layer of mesothelial cells that line the abdominal cavity and its organs. In normal conditions (homeostasis), it provides a gliding surface for the organs. When damaged, the resulting scars can develop into fibrotic lesions that can cause adhesion between organs or with peritoneal tissue. Peritoneal fibrosis following long term dialysis, endometriosis, post-surgical adhesions, for example, are some of the conditions involving peritoneal scarring and fibrosis. In this project, we are interested in understanding the principles of homeostasis and scar formation in the peritoneum. We will look into different molecular pathways that might be involved in cell differentiation during scar formation and fibrosis, using primary samples from patients. This project hopefully will uncover some of the molecular mechanisms of scarring and open new paths towards understanding and treatments of those diseases.
Leela Ghimire
Newcastle University
Supervisor: Prof Tracy Palmer
Project title: Characterisation of a novel secretion system
Secretion systems in bacteria play an important role in their pathogenicity. The type VI (T6SS) and type VII secretion systems (T7SS) found in gram negative and gram-positive bacteria respectively are responsible for secreting effector proteins including toxins which cause infections and diseases. Recently, bioinformatic analysis of Bacillota revealed unique loci which encode proteins analogous to T6SS components along with toxins like those found in T7SS. This combination is remarkable since T6SS are usually only found in gram positive bacteria. The aim of my project is to bring to light features of this newly discovered secretion system and characterise toxins associated with it. Studying this secretion system structurally and mechanistically has great implication not only for furthered understanding of protein secretion but also for translational aspects like development of therapeutic strategies.
Kyle Walker
University of Liverpool
Supervisor: Dr Marcus Blagrove
Project title: Does the natural larval habitat of a mosquito affect its ability to transmit viruses?
Due to climate change and anthropogenic factors such as increased movement of people and goods, the UK is at an increased risk of mosquito-borne disease. This is most evident in the detection of Usutu virus in Greater London every summer since 2020. The primary vectors of both Usutu and the closely related West Nile virus are mosquitoes of the Culex pipiens complex. Due to the emergence of Usutu in the UK and West Nile in northern Europe, it is imperative to gain better understanding of these mosquitoes and their habitats. Larval habitats in particular are pivotal in the mosquito lifecycle during their early aquatic stages. My project will focus on the physicochemical properties of these habitats, whether specific properties attract specific mosquitoes, and whether they have a knock-on effect on the vector competence traits of the adults that emerge. This information will in turn aid surveillance efforts that monitor the spread of these species to better inform control strategies and prevention of future mosquito-borne disease outbreaks.
Hal Flowerdew
Newcastle University
Supervisor: Dr Katarzyna Mickiewicz
Project title: Characterisation of physiological properties and pathogenic potential of mycobacterial L-forms
Antimicrobial resistance stands as a global threat. It is an issue that is causing more deaths annually. One such disease which is of vast concern is that of Tuberculosis, with 1 in 3 new antimicrobial infections being TB related. Mycobacteria are a unique family of bacteria, in that their cell envelope is very unique. it is comprised of four layers, with a double membrane, and it is a mycolic-acid-rich cell wall made up of peptidoglycan and arabinogalactan. This means mycobacterial infections require unique treatment, which tends to be hyper-specific to the cell wall. However, there is evidence that suggests that a way in which mycobacteria may persist is through the entire loss of the cell wall, via L-form switching. This is a process that has been associated with other persistent infections such as recurrent UTIs. Therefore the project aims to identify and research these mycobacteria in an L-form state, in the hopes of helping in the battle against antimicrobial resistance. In addition, this project is a CASE studentship and offers a unique opportunity to work with Nanovery to develop a nanorobot diagnostic tool for bacteria.
George Batten
Newcastle University
Supervisor: Dr Patricia Lopez-Calcagno
Project title: Enhancing Crop Resilience and Productivity: Investigating relationships between Plant Photosynthetic Efficiency, Pest Defence, and Microbial Interactions for Sustainable Agriculture
The interplay between the community around the plant, including rhizobacteria and pests, and how these might change depending on the plant's photosynthetic capacity remains largely unexplored. It is known that plants exhibit a different response to insect herbivory when exposed to elevated CO2. Yet, it is unknown to what extent changes in photosynthetic capacity affect the plant's C/N ratio and their relationships with insects, pests and the microbial communities in their vicinity. This project investigates the interplay between defence-inducing rhizobacteria, pests - we will focus on aphids and caterpillars, and plants with different photosynthetic efficiency. Utilising both GM and non-GM germplasm to address this question under controlled conditions and agricultural settings, we aim to understand the effect that breeding for increased productivity through increasing photosynthetic capacity will have in the communities around the plant.
Hong Chen
University of Liverpool
Supervisor: Dr Manolis Papamichos Chronakis
Project title: Quality control mechanisms of mRNA biogenesis
Epigenetic control of gene expression is essential for cell viability, differentiation and identity. Deregulated epigenome contributes to disease, including oncogenesis. Transcription, the first step in gene expression, underpins life. Elimination of non-functional transcripts is vital for proper gene expression and of paramount importance to cellular homeostasis. In eukaryotes, nuclear RNA surveillance and termination of aberrant transcription is an established, pivotal facet of cellular stability. Notably, despite advancements, an existing knowledge gap persists regarding the molecular mechanisms underpinning the identification and abortion of aberrant transcription by RNA polymerase II. This project is designed to bridge this gap and illuminate the pathways that safeguard RNA quality control, with the potential of providing fresh insight into the complexity of metazoan gene expression and the role of RNA quality control in disease.
Heiloi (Louie) Yip
Newcastle University
Supervisor: Dr Vivek Nityananda
Project title: Insect-inspired pattern recognition with low computing power
Bees have miniature brains compared to humans, but manage to perform impressive feats of visual behaviour. They can learn concepts, discriminate complex patterns and assess quantities. While these achievements are well documented we know less about how bees manage to perform these tasks. Some recent research has argued that they do so using active vision - combining movement patterns and visual input. By using stereotypical flight movements and assessing the visual input, bees in effect convert complex visual problems into simpler ones. My PhD project will investigate how bees use active vision in pattern recognition tasks and develop algorithms based on their behaviour that can be used for technological applications. Understanding how they do this is especially promising for technological innovations as it would allow robots with low computational processing power to nonetheless perform seemingly complex tasks.
Jake Bell
University of Liverpool
Supervisor: Dr Igor Barsukov
Project title: Investigating the link between ageing, neurodegeneration and maintenance of axonal microtubules through EB1 phosphorylation: from structures to Drosophila models
Neurodegenerative disorders, such as Alzheimer's Disease, are a growing global health concern, significantly impacting the quality of life for millions of individuals. These conditions are characterised by neuronal dysfunction often linked to the breakdown of axonal microtubule bundles (MTs). In Drosophila ageing models, MT degradation has been observed before overall cellular dysfunction, highlighting the importance of MT maintenance. One potential therapeutic target is the plus end-tracking protein end-binding protein 1 (EB1), which facilitates the recruitment of microtubule-associated proteins (MAPs) to the damaged MTs, promoting repairs. Post-translational modifications, such as phosphorylation regulate the interactions between EB1, MAPs, and consequently its protective role on MTs. Importantly, however, the effect of phosphorylation on EB1 and its affinity to MAPs changes throughout ageing. Consequently, there is a need to investigate how EB1 interaction networks change in response to phosphorylation/dephosphorylation in a neurodegenerative context. Therefore, I will utilise NMR and X-ray crystallography to solve structures of the EB1 complexes and network assembly in vitro and in cells. I will then disrupt specific EB1 interactions in Drosophila ageing models and monitor the age-related MT stability to understand the role of specific interactions in MT maintenance. This project presents opportunities for better understanding potential therapeutic targets for neurodegenerative disorders.
Jo Stokell
Newcastle University
Supervisor: Dr Agnieszka K Bronowska
Project title: Development of lysine-targeting irreversible chemical probes for selective inhibition of protein targets
Irreversible covalent targeting of proteins using small molecule probes and inhibitors offers prolonged target engagement, improve potency, enhanced selectivity and the option to hit traditionally "undruggable" sites. Traditionally, covalent drugs are designed to react with solvent-exposed cystine residues, however this approach has two major limitations: they are not applicable to protein targets which do not possess accessible, reactive cysteines, and they do not bypass the problem of acquired drug resistance that has emerged in, for example, small-molecule kinase inhibitors. Lysine is one of the most abundant amino acids present in a protein and offers an alternative target for covalent strategies. The first stage of this project is the further development and optimisation of a 2-ethynylbenzaldehyde (EBA)-based, lysine-targeting “warhead”, that targets the MenT1 toxin by formed adducts with essential K137 residue of MenT1. The overall aim of this project is to further validate the generality of this strategy by structure-based development of lysine-targeting irreversible chemical probes targeting MenT12 (mycobacterial toxin) and pyrin domain (PYD)3 of mammalian NLRP3 inflammasome, demonstrating transferability of this approach and applicability of selective lysine-targeting to structurally and functionally diverse protein targets.
Molly Keen
University of Liverpool
Supervisor: Dr Krystyna Cwiklinski
Project title: Understanding the impact of parasitic co-infections on animal immune health in UK sheep
Sheep in the UK are exposed to several economically important helminth parasites during the grazing/production season. These can result in disease that impacts animal growth rates and quality of meat, wool and milk to name a few. Anthelmintic resistance has been reported for current drug classes in use and vaccines may offer a new means of prevention. However, the complexities of host-parasite interactions and the impact of multiple parasite exposures on the pasture needs to be considered for the development of efficacious vaccines. This project aims to investigate the occurrence of parasite co-infections in sheep, and understand how this impacts host immune responses over the grazing/production season. This will be split into two key means of investigation: 1. Analysis of parasite prevalence in UK sheep flocks over multiple grazing seasons using faecal and serological diagnostic techniques. In conjunction with questionnaires on farming practices and parasite management, this data will be used to identify patterns of co-infections that can be interpreted into management of parasite control in sheep. 2. Systematic immune responses to parasite infections will be investigated using in vitro cellular assays and transcriptomic analysis of PBMC’s collected throughout the grazing season. This will determine the immune profile being driven by parasite infections which can be incorporated into the vaccine strategy.
Neha Manoj Ramchandani
Newcastle University
Supervisor: Dr Henrik Strahl
Project title: Interplay between bacterial multidrug efflux and outer membrane permeability creates an unexpected vulnerability towards antibiotics
Antibiotic resistance (AMR) is a serious global health emergency that increasingly challenges our ability to treat life-threatening infections. To tackle this major threat to our health, it is critical to develop new and innovative therapeutics that are less prone to AMR development. Recently, it was discovered that the multidrug efflux and outer membrane permeability barrier, two key processes implicated in AMR, are surprisingly closely interlinked. My project involves studying this newly identified cellular link to uncover exciting insights into the mechanisms through which bacteria evolve and acquire antibiotic resistance, while also identifying vulnerabilities that can be exploited for the development of drugs and drug combinations that are less prone to AMR development.
Ana-Mariya Anhel Valdes
University of Liverpool
Supervisor: Dr Jamie Soul
Project title: Omic data integration and machine learning to define molecular drivers of chondrogenesis
Cartilage is a strong, flexible connective tissue that protects joints and bones. It plays a crucial role in our daily activities like walking or bending. Damage to this tissue can cause pain and stiffness, reducing joint mobility. Since cartilage lacks a blood supply, it has a limited ability to heal, making research into its regeneration vital for developing new treatments. Cartilage formation, or chondrogenesis, occurs when mesenchymal stem cells differentiate into chondrocytes, a process influenced by various molecular regulators. This project aims to uncover new regulators of this process. For that purpose, we will use a high-throughput omics database developed by my supervisor's team and network-based approaches to track molecular pathways that have been altered during in-vitro chondrogenesis. This pathway information, alongside already known regulators of chondrogenesis from biomedical literature, will be used as an input of machine learning algorithms to obtain new chondrogenesis regulators. Newly identified factors will be tested to assess their ability to drive mesenchymal cells to differentiate into chondrocytes. These findings could lead to novel treatments for cartilage-related diseases, benefiting millions of patients. The project will also enhance our understanding of how combining large omics databases can uncover cell differentiation regulators.
Finn Brady
Newcastle University
Supervisor: Dr Jon Marles-Wright
Project title: Using structural biology and biochemistry to study environmental stress sensing by bacterial stressosome complexes
To adapt to an ever-changing environment, bacteria must be able to sense changes in their environment and produce an appropriate response. Proteins embedded in the cell membrane can detect changes in the external environment, and sensors inside the cell can monitor cellular conditions. These protein sensors can directly or indirectly influence gene expression to reprogram the cell to respond to a change in conditions and ensure its survival. The stressosome is a multi-protein complex made up of sensor proteins and a protein kinase. This acts as a signal integration hub, transducing signals into a response, such as a change in gene expression. The stressosome is present in many bacterial species, including Bacillus subtilis, Listeria monocytogenes and Vibrio vulnificus. Despite the important role the stressosome complex plays in the survival and adaptation of these bacteria, the signals which activate the stressosome have not been clearly identified. During the project, I will conduct a structural investigation into the native stressosome complex from Bacillus and Listeria species using molecular microbiology techniques, protein purification, single-particle cryogenic electron microscopy (cryo-EM) and machine learning.
Isaac White
University of Liverpool
Supervisor: Dr Dan Canniffe
Project title: The evolution of oxygen tolerance
The phototrophic alphaproteobacterium Blastochloris viridis has received attention in recent years owing to its unique ability to perform photosynthesis by capturing extremely long wavelength light, creating opportunities to utilise underused wavelengths of light for biotechnological purposes. However, culturing this bacterium in the lab is difficult - predominantly due to its poor tolerance of oxygen, meaning characterisation and manipulation has to be performed in strict anaerobic environments. This project will aim to accomplish three objectives: 1) Using directed evolution techniques, we aim to generate an oxygen tolerant variant of Blastochloris viridis to allow us to more easily tap into its biotechnological potential; 2) We will attempt to use insights gained in the evolutionary experiments to delineate a general ‘anaerobe to aerobe’ pipeline for use in other stubborn anaerobes and 3) We hope to provide some answers to the questions of precisely how tolerance to oxygen evolved during the Great Oxygenation Event on an early Earth.
Gemma Bell
University of Liverpool
Supervisor: Prof Sonia Rocha
Project title: How hypoxia regulates the histone methylation cycle, role of the MAT2 complex
My project aims to investigate how the histone methylation cycle is regulated through the methionine adenosyltransferases (MAT2) complex in hypoxia. In hypoxia the levels of Hypoxia-inducible factor (HIF) increase which leads to increased chromatin accessibility and increased transcription of hypoxia related genes. Chromatin accessibility can be regulated through methylation. This is controlled in different ways, one of which being through the production of S-Adenosylmethionine (SAMe) a methyl donor – which is synthesized by MAT2. As SAMe levels are dysregulated in cancer it is likely that hypoxia alters MAT2’s normal function. Therefore, my PhD project will look at how MAT2 changes in hypoxia, investigating potential binding partners and how it contributes to the hypoxic response. Additionally, the impact of MAT2 on gene expression through the regulation of the histone methylation cycle.
Eve Apostel
Newcastle University
Supervisor: Prof Nick Jakubovics
Project title: Ultrasmall bacteria for oral biofilm control
The oral microbiome is diverse, consisting of a plethora of different microorganisms, including bacteria, microeukaryotes, archaea, and viruses. Through the use of metagenome sequencing, ultrasmall candidate phyla radiation bacteria (CPR) have been discovered. The CPR group is ubiquitous within microbial communities, accounting for 25–50% of bacterial diversity on Earth. However, it remained uncultured until 2015, when the TM7 group was co-cultured with another bacterium. Formally known as Saccharibacteria, these tiny obligate epibiont bacteria have a reduced genome and are incredibly host-specific. Interestingly, several different TM7 bacteria have been identified within the oral microbiome and have been linked to inflammatory conditions, including gingivitis and periodontal disease. Despite the isolation of several TM7 bacteria from the oral cavity, their physiology and mechanisms of pathogenesis remain unknown. Therefore, the aim of the iCASE project is to characterise cell-cell interactions between TM7 and host bacteria to be able to determine the mechanisms of host cell specificity and pathogenesis.
Cherry Bedford
University of Liverpool
Supervisor: Dr Matthew Barden
Project title: Harnessing Phenotypic and Genomic Data to Reduce Lameness in Dairy Cattle
This project will initially use simulated data to assess and develop variable selection methods for GWAS. Subsequently, data from recent or ongoing projects will be analysed, specifically a dataset of around 5,000 genotyped cattle with computer vision phenotypes, and a large dataset of foot lesion records collated from foot-trimmers. These data will support GWAS of novel computer vision lameness-associated traits, and the estimation and validation of foot lesion breeding values, calculated within a single-step framework. Foot lesion data will be merged with farm records, through collaboration with the industry partner, to quantify herd survival associated with each foot lesion, and to estimate the environmental cost of foot lesions by incorporating these results into a whole-farm simulation model.
Cameron Westland
Durham University
Supervisor: Dr Vincent Croset
Project title: Dopamine transport and the modulation of learning and memory in Drosophila
Dopamine plays several essential roles in cognitive processes, including learning, memory, and motivation. The dopamine transporter (DAT) is responsible for dopamine reuptake from the synaptic cleft, thereby controlling dopamine temporal dynamics, and concentration and diffusion in extracellular space. DAT is central to neurological conditions such as depression, ADHD, Parkinson’s, and addiction. This project utilises cutting-edge technologies to investigate how dopamine transport affects behaviour, metabolism, and gene expression in the Drosophila melanogaster brain. Recent data suggest a context-dependent function of DAT in promoting either learning or forgetting, and I aim to understand further how this balance is adjusted. Furthermore, I will investigate DAT’s role in preventing dopamine spillover between adjacent but functionally distinct dopaminergic synapses, and to decipher the long-term consequences of disrupted dopamine reuptake across the life course. These experiments will focus particularly on elucidating the role of recently discovered DAT expression in post-synaptic partners of memory-relevant dopaminergic neurons. It is anticipated that increased extracellular dopamine levels resulting from the dysregulation of dopamine transport may lead to the accumulation of toxic catabolites and contribute to neurodegeneration, and may also influence the expression of genes involved in the response to oxidative stress, homeostasis, mitochondrial function, or neurotransmission, Using RNA-sequencing and metabolomics, I will identify these molecules to highlight the molecular consequences of dopamine transport disruption, and identify candidate compounds linked to age-dependent loss of memory performance.
Maxym Besh
University of Liverpool
Supervisor: Prof Luning Liu
Project title: Synthetic engineering of cyanobacterial CO2-concentrating mechanisms for enhanced carbon assimilation
CO2 levels in the atmosphere, being a large contributor to the Green House Effect, continue increasing yearly, despite efforts to prevent that. Net Zero Coalition’s plans to avoid the 2-degree Celsius increase in global temperatures (above pre-industrial levels) have included a component of carbon capture, which is the removal of CO2 from the atmosphere. However, conventional chemical-based carbon capture systems might not be sufficient to meet global demand. The alternative is to use cyanobacteria that is already capable of carbon assimilation and utilisation. The aim of my project is to enhance the existing mechanism of CO2 breakdown present in cyanobacteria by making the breakdown process highly productive, controllable, scalable, and sustainable for underpinning biomass and biofuel production under different environmental conditions. The project is run in collaboration with an industry partner Cyanocapture.
Mantas Jonaitis
University of Liverpool
Supervisor: Dr David Turner
Project title: Uncovering the role of NF-κB2 in embryonic stem cell pluripotency and differentiation
Understanding the regulation of cell fate decisions is a fundamental objective in developmental and stem cell biology. During early development, embryonic stem cells possess unlimited potential and can differentiate into all cell types in the body. The decision to maintain or commit to a specific fate is tightly regulated by a complex network of signalling pathways. While Nuclear Factor kappa B (NF-κB) signalling is implicated in many cell fate decisions, its role in early development remains underexplored and highly controversial. In this project, we will combine bulk-cell techniques with single-cell analysis using immunofluorescence and fluorescently tagged NF-κB2 proteins to visualise its dynamics and lineage-specific reporter expression during cell fate decisions in mouse embryonic stem cells (mESCs). This will be complemented by experiments using small-molecule inhibitors to disrupt upstream components of NF-κB signalling and assess their impact on pluripotency and differentiation. These approaches will allow us to uncover the fundamental principles guiding cell fate decisions during early embryonic development and how the interplay between NF-κB, cell states, and chemical signalling orchestrates these decisions.
Sophia Johnson
Newcastle University
Supervisor: Dr Adam Wollman
Project title: Lightsheet microscopy to uncover the architecture of gene regulation in human cells and its role in cancer
Many diseases have been linked to aberrant transcription factor (TF) behaviour such as the NF-kB TF family that can promote the proliferation of a range of cancers. Despite this, we do not fully understand the mechanisms behind how TFs find their targets and possess specificity for the correct genomic loci. Many imaging labs have discovered that TFs including NF-kB operate in clusters or “condensates” especially at super enhancers which may be key to their specificity and target finding. This project will utilise novel microscopy combined with genomic technologies to map the 3D structure and mechanical properties of the DNA NF-kB is binding to. This would allow us to understand why clustering occurs and how it could be therapeutically targeted for cancer.
Madeline Park
Newcastle University
Supervisor: Dr Catriona Anderson
Project title: Targeting Nutrient Transport in Insect Pests for the Development of Novel Crop Protection Tools
Sap-feeding insects such as aphids, spittlebug and whitefly are global pests for crops including potatoes, grapes and olives. The sap that these insect species feed on is low in essential amino acids and therefore these species have evolved symbiotic relationships with intracellular bacteria to meet this nutritional need. At the heart of this relationship is the ability for amino acids and other nutrients to be exchanged between insect and bacteria. This project aims to identify transporter proteins integral to the symbiotic relationship and to test inhibitors that may disrupt nutrient transport. In partnership with Fera Science this CASE studentship aims to enable the development of novel crop protection tools which are specific for existing and potential future UK pest species
Benjamin Shone
Durham University
Supervisor: Dr Jungnam Cho
Project title: Understanding the host recognition of nonself alien DNA and initiation of epigenetic silencing
Transposable elements (TEs) are mobile sections of DNA capable of moving to different locations within the genome. This is typically achieved via a “cut and paste” or “copy and paste” mechanism, depending on the class of TE. Up to 90% of some cereal crop genomes are formed of TEs. The mobilisation of these TEs can lead to significant genomic changes such as, frameshifts, gene duplication, translocations and inversions. The genomic diversity promoted by TE mobilisation can be desirable for crop plants as it can lead to favourable phenotypes for production and consumption. However, these genomic changes can also be detrimental, potentially resulting harmful mutations or promotion of oncogenes in eukaryotic cells. This project will analyse how TEs are regulated via epigenetic pathways and how these pathways can be influenced to promote positive TE effects, such as transgene stability in crop plants, whilst discouraging pathological features.
Charlotte Malpass
Durham University
Supervisor: Dr David Doupe
Project title: Signalling Dynamics in Intestinal Stem Cell Homeostasis and Ageing
The intestinal epithelium undergoes constant turnover, with intestinal stem cells (ISCs) essential for balancing proliferation and differentiation to maintain tissue homeostasis. Ageing, however, disrupts this balance, impairing function and signalling pathways. Although many of the regulatory signals have been identified, the temporal dynamics involved and how they interact remain poorly understood. This is especially important since the same pathways are often reused in various biological contexts, with temporal changes being a key factor in enabling diverse outcomes. This project aims to understand the importance of signalling dynamics in stem cell regulation in vivo, through the widely recognised usage of Drosophila ISCs, providing an excellent model for mammalian ISCs due to their conserved pathways. By using live intravital confocal imaging, fluorescent pathway reporters, and deep learning-based image processing, we will explore how pathway interactions change with age, to test whether altering signalling dynamics can shift cell fate and restore homeostasis, through: 1. Measuring signalling pathway dynamics in ISCs in vivo during homeostasis and ageing. 2. Characterising the regulatory mechanisms that drive these dynamics. 3. Manipulating dynamics to change cell fate. Overall, these findings will provide key insights into stem cell regulation and ageing, with implications for human intestinal health.
Ellie Harland
University of Liverpool
Supervisor: Prof Caroline Dart
Project title: Molecular, biophysical and regulatory characterisation of ion transport pathways in the human skin apocrine gland
Skin is the largest organ in the human body and forms a protective layer against the environment. While the human eccrine sweat gland is known to be crucial in cooling the body by secreting a salty fluid (sweat) onto the skin surface, the function of the apocrine sweat gland is less clear. Apocrine glands located in the axillae (underarm) secrete a milky fluid into the lumen of the hair follicle which is subsequently metabolised by bacteria to produce malodorous compounds. They are not thought to participate in thermoregulation and little is known about their function or the molecular mechanisms that drive apocrine secretion. Therefore, my Unilever-sponsored CASE PhD project will use a multi-disciplinary approach, to characterise the molecular and regulatory mechanisms involved in apocrine sweat production. The ultimate aim of the project is to provide the first integrated model of ion transport systems involved in apocrine sweat gland secretory cells.
Joshua Underwood
University of Liverpool
Supervisor: Dr Nick Fallon
Project title: An Investigation of the Neural Basis of Changes in Tactile Acuity During Healthy Ageing and its Impact on Emotional Wellbeing
The sense of touch involves perceiving tactile stimuli through mechanoreceptors in the skin and joints, integrating both tactile and proprioceptive inputs. During tactile exploration, humans rely on their hands, which have a high density of mechanoreceptors providing sensory acuity. However, this acuity declines with age, affecting interactions with external stimuli. Age-related declines in passive tactile acuity are linked to changes in the peripheral nervous system, while active exploration declines later, suggesting central nervous system mechanisms may play a role. Aging also affects motor control and GABA levels, potentially leading to compensatory neural processing in active touch. Recent lab research explored brain activation during tactile exploration and the hedonic properties of touch, advancing understanding of active touch mechanisms. Although this research didn't focus on aging, the link between touch and emotional well-being suggests that declining tactile acuity may impact quality of life. This project aims to address this by examining the central mechanisms behind age-related declines in tactile acuity, with potential applications for improving aging outcomes.