RNA splicing regulation by RNA modifications

How do RNA modifications regulate gene expression in the germ cells? Our RNA (epi)genetics laboratory addresses this broad question using the nematode Caenorhabditis elegans as an animal model. Germline stem cells are essential for the survival of organisms by giving rise to offspring. Gene expression changes within the germ cells can affect embryonic development, and in some organisms, such changes are transgenerationally inherited. RNA is at the centre of many

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Feeling the force of fungi: A novel role for piezo1 in the cellular detection of fungal invasion

The fungal mould Aspergillus fumigatus represents a significant threat to the health of humans and animals. A. fumigatus spores are inhaled daily, but in organisms with weakened immune systems, inhalation can be life-threatening. Once inside an organism, A. fumigatus germinates to produce vine-like structures called hyphae. These hyphae break through the lung and into the bloodstream, leading to fungal growth throughout the body. The question we aim to ask is, how do cells know that they are being invaded and how do they respond?

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Light-Triggered Enzyme Catalysis Inside Vesicle Microreactors

This exciting project will engineer light-driven microreactors converting nitrate to ammonia thereby delivering proof-of-principle for a sustainable technology converting a widespread pollutant to a valuable fertiliser and chemical feedstock.

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New strategies for pest insect control by population suppression

Pioneering solutions for pest insect control are urgently needed, as climate change is increasingly driving pests into new geographic areas. The student will address this critical challenge for innovative control solutions by developing new methods for managing key insect pests. The focus will be the Mediterranean fruit fly (Ceratitis capitata, medfly), which is moving into new environments including the UK, and poses a growing threat to agriculture and food security.

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More than one route to fertility

Male sexual traits are notoriously variable, which is puzzling, as traits essential for fitness are expected to exhibit low variation due to strong directional selection. Though many solutions have been proposed, we still lack satisfactory, general explanations. A good example in found in Drosophila melanogaster, in which there are over 250 seminal fluid compounds that have essential functions, but which also exhibit substantial diversity. It remains unclear why some seminal fluid proteins have multiple functions, some only one, and why there is

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Understanding molecular wires involved in enhancing bacterial electricity.

Bacteria that can produce electricity are being intensively researched due to their potential applications in metal recovery, desalination and enhanced fermentation. The model microorganism Geobacter sulfurreducens is one of the most efficient producers of bioelectricity, and the current production has been linked a single extABCD gene cluster. Our preliminary characterisation of the products of this gene cluster reveals that it contains 3 cytochromes with unique and distinct heme clusters. This project aims to fully understand the properties

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Controlling greenhouse gas emissions by targeting G-quadruplex DNA/RNA structures in plant-associated bacteria

As well as carbon dioxide (CO2), other important climate-active gases are known to drive global warming. Importantly, nitrous oxide (N2O) also known as laughing gas, is the third most abundant greenhouse gas with 300-times greater global warming power than CO2 and it also contributes to the destruction of the ozone layer. Production of N2O is a by-product of

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Tailoring building blocks for carbohydrate assemblies: combined NMR and computational approach

Imagine a world free of oil-based plastics where biodegradable materials based on carbohydrates, the most abundant polymers on Earth, reigned supreme. Carbohydrates fulfil many important biological functions ranging from their ability to impart molecular recognition within (cell wall structure) and between species (infection). The natural self-assembly of sugar chains into complex 3D architectures is central to these functions, and also to widespread applications in food, packaging, pharmaceutical tabletting etc. Cellulose is widely used

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Elucidating Biophysics of Starch Granule Assembly

Wheat is by far the UK’s most important crop in terms of production and wheat-based foods are a staple component of our diet. Most of the calories from wheat grains come from starch, which comprises ~80% of the grain weight. We still do not fully understand how starch is synthesised during grain development. Recently our team have identified a set of conserved proteins that control the number and timing of starch granules formation. By mutating the genes that encode these proteins, they have

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Dissecting calcium signalling in Marchantia polymorpha

Plants need to respond to the environment in order to adapt and grow. Plants often modify the concentration of calcium ions in their cells in response to different environmental stimuli and stresses [1]. These changes in cellular calcium concentration trigger many downstream responses, including re-programming of gene expression. Calcium signalling pathways are therefore essential for plants to respond and adapt to environmental stimuli and stresses.

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Hematopoietic specification using single-cell in vivo CRISPR screen

Are you passionate about revolutionary research in stem cell biology, gene regulation, and cutting-edge molecular techniques? Join our innovative project, Hematopoietic Specification Using Single-Cell In Vivo CRISPR Screen, where you will delve into the genetic blueprint of blood formation and make impactful discoveries with real-world applications.

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Signalling pathways that mediate the dual origins of the dorsal aorta

Embryo development is a fascinating process generating a highly organised body plan with many features that are conserved across different vertebrate species. This includes the metameric organization of the vertebrae and the associated skeletal muscles, nerves and blood vessels, produced by somites residing on each side of the neural tube. In previous work, we have determined molecular profiles of somites and adjacent tissues along the anterior-posterior axis of developing chick embryos. This identified accessible chromatin, differentially

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Passerine viromics and genomics - a One Health approach to understanding infectious disease

Passerine birds are often closely associated with humans but very little is known about their viromes despite them hosting viruses that cause disease in humans and domestic animals Furthermore, the extent to which passerines can catch and transmit viruses from other species, including reservoirs of key viral pathogens, such as seabirds, is unknown1. Finally, determining what genomic characteristics enable passerines to combat viral challenges can provide insight into the evolved traits and mechanisms that may help us mitigate such

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The mechanistic and physiological significance of Hfq in bacterial sRNA regulation of greenhouse gas emissions

Nitrous oxide (N2O) is a major greenhouse gas, with 300-fold greater warming potential than carbon dioxide. A major source of N2O comes from soil microbes utilising nitrogen-based fertilisers rather than oxygen to breathe in a process called denitrification. The final step in denitrification, the reduction of N2O to N2, is carried out by the enzyme nitrous oxide reductase, NosZ. However, NosZ does not always work in natural environments, and we know that denitrifying organisms make a substantial contribution to N2O emissions. An

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Is glutamine the answer to reversing blood stem cell ageing

As our ageing population grows it is becoming increasingly important to better understand the changes that occur during physiological ageing. Ageing drives intrinsic metabolic changes that alter normal physiology and result in tissue dysfunction and the development of numerous age-related diseases. This project will aim to better understand the age-related metabolic changes that occur in blood stem cells with a focus on glutamine metabolism and the impact this has on blood production. Whilst our previous work has demonstrated that

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Investigating the recovery of blood stem cells from infection

The ability of haematopoietic stem cells (HSC) to expand and differentiate is key to normal homeostasis and the systemic immune response. HSCs promote a rapid immune response by generating innate and adaptive immune cells that are recruited to the site of infection. After the infection has been overcome HSC numbers decline to pre-infection levels, however what controls this reduction in numbers is not known. Our laboratory has shown that the non-haematopoietic cells (fibroblasts and adipocytes) support HSC maintenance in the

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Molecular cross-talk between copper and zinc resistance in pathogenic bacteria

Group B Streptococcus (GBS) is an effective pathogen of humans and animals and is well known as the leading cause of often-fatal infections in newborn infants. Little is known about how GBS resists the immune system and colonises to cause invasive disease. This PhD will develop a new understanding of how streptococci resist intoxication by metals, a major antimicrobial effector of the human innate immune system. It will investigate how GBS controls a network of genes to counteract toxicity of zinc (Zn) and copper (Cu) when in

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Bioproducing a weight loss fibre product from algal waste

Demand for natural weight loss remedies is exceptionally high. With Central Pharma Biotechnica Limited (Biotechnica), this PhD aims to develop a cost-effective and low carbon emission, microbial route to bioproduce a high-value weight loss fibre product from seaweed waste. Currently, our seaweed-derived fibre contains sulfur molecules that confer it bad tastes and smells. Microbial fermentation is our chosen route to safely remove these compounds. Our product would enhance the seaweed industry and offer natural and safe routes to

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Unveiling a key enzyme in global sulfur cycling

Billions of tonnes of the osmolyte dimethysulfonioproprionate (DMSP) are produced annually in Earth’s oceans by many algae and bacteria. These organisms produce DMSP at mM intracellular concentrations for protection against varied stresses. When released into the environment, microorganisms import and catabolise DMSP, generating the climate-cooling gas and signalling molecule dimethylsulfide (DMS) via DMSP lyase enzymes. However, marine microbes can also oxidise DMSP to form

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Searching for buried treasure: extraction of high-value pharmaceutical ingredients from seaweed fertiliser and waste

The use of seaweed as a raw material is a rapidly growing area with enormous commercial potential. Unlike conventional land-based sources or fossil-fuels, seaweed acts as a carbon sink and does not require land, water or fertiliser to grow. With Central Pharma Biotechnica Limited (Biotechnica), this PhD aims to develop a cost-effective route to bio-produce high-value ingredients including phlorotannins (antivirals), fucoidans (digestive health) and alginates (pharmaceutical materials) from harvested seaweed. Currently, the raw

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Engineering the yeast cytochrome bc1 complex for the development of new antifungal inhibitors

Cytochrome (cyt) bc1 complexes are central to electron transport chains in many species of bacteria and in mitochondria. The essentiality of this complex makes it a promising target for the development of new compounds that target human and plant pathogens. However, producing pure proteins from these pathogens in a laboratory environment is challenging because these organisms are often not genetically tractable, cannot be cultured on large

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Developing and industrialising attachment of chemical probes to monitor biological events

We use biophysical methods to study the architecture and functional dynamics of membrane proteins, especially many medically-relevant membrane transport systems. There is increasing evidence that membrane proteins do not act alone, but that they are organised as nano-machines which function through the concerted action of individual components with high precision and specificity observed in both time and space. We are seeking to unravel the principles underlying the architecture and dynamics of these protein nano-machines as well as their function.

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The Role of AGMO - alkylglycerol monooxygenase - in development

The canonical Wnt pathway is a potent signalling system that regulates numerous processes during embryonic development, including cell fate determination, migration, polarity, proliferation, and apoptosis, as well as stem cell biology and adult tissue homeostasis. Dysregulated Wnt signalling contributes to many diseases, including birth defects, neurodegeneration, and cancers. As a result, investigation of the Wnt pathway, and identification of Wnt regulators, is considered a research priority.

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