(Previously Future Leader fellows)
Interested in becoming a fellow? Go to the Discovery Fellowships page (in Funding section).
For details of all current Discovery fellows, please use the links below
Dr Sam Amsbury, University of Sheffield
Disentangling plant cell walls: the characterisation of dynamic polysaccharide interactions in the developing cell wall
Plant cell walls are polysaccharide networks surrounding all plant cells fulfilling crucial structural roles during plant development, cell walls are also a renewable resource being a huge source of biomass. The complexity of the cell wall is extraordinary and understanding their structure has proved extremely challenging and the link between cell wall composition and plant physiology is not well understood. The aim of my research is to understand cell wall responses to environmental fluctuations. In the first part of the project I will characterise polysaccharide interactions within the cell wall during plant development and in response to abiotic stresses to understand environmental drivers of cell wall composition. In the second part of the project I will identify novel cell wall regulatory genes that are related to abiotic stress to understand the genetic drivers behind the cell wall responses identified in phase I.
Dr Magdalena Czubala, Cardiff University
Eosinophil and macrophage crosstalk defines cell survival and modulates local tissue niche
Tissue resident immune cells, such as macrophages, are crucial for maintaining tissue homeostasis. Different types of immune cells communicate and instruct each other in this complex process. Disruption to this communication leads to tissue damage and prolonged healing.
My research focuses on interactions between two immune cells, macrophages and eosinophil, and how this crosstalk influence cells’ biology and tissue health. During the fellowship, I will combine aspects of immunology and lipidomics to decipher the role of lipids in cell communication. My data suggests that macrophages dictate the survival and function of eosinophil in tissue via lipid signalling. This is particularly important, because the reasons for eosinophil accumulation in tissues remain poorly understood, and hypereosinophilia leads to diseases, such as asthma and atopic dermatitis. I will further investigate how we can manipulate macrophage-eosinophil communication to maintain and restore healthy tissues.
Dr Melanie Eckersley-Maslin, Babraham Institute
Dppa2/4 regulate the epigenome during gastrulation
Embryo development is a remarkable process. Following fertilisation of the egg by the sperm, the embryo must grow from a single cell capable of becoming any part of the body to an ordered group of cells each with their own identity. This requires tight regulation and control however we have a limited understanding of how this is achieved.
I have recently identified 2 factors which ‘epigenetically prime’ the genome in embryonic stem cells. These factors are required to establish a permissive chromatin landscape at key developmental genes enabling them to be appropriately activated at later stages of development. My research will investigate how these factors function at a molecular level and their impact on the function of the cell. I will be using a combination of stem cell cultures and animal models and cutting-edge single-cell and epigenomic technologies. My research not only builds our basic understanding of developmental biology but could also help improve regenerative medicine and stem cell therapies.
Dr Ian Lidbury, University of Sheffield
Discovering novel microbial tools to mitigate the global phosphorus crisis: Identification of unique phosphatases in abundant rhizobacteria
To produce enough food from plants to feed an increasing global population, farmers apply excessive quantities of chemical phosphorus fertilisers, such as rock phosphate. Unfortunately, rock phosphate is a non-renewable resource that will likely be exhausted within 50-200 years. This presents an emerging global crisis to the world food supply chain. Soils contain a natural reserve of phosphorus, but this is largely unavailable to the plant without prior transformation to an available form, orthophosphate. Developing new and sustainable ways to transform this natural reserve is essential for mitigating the global phosphorus crisis.
Microorganisms living in close proximity to plant roots help plants acquire phosphorus by releasing orthophosphate from this natural reserve. Ian recently discovered that an enigmatic group of root-associated bacteria possess enormous potential to perform this process through the expression of novel and unusual enzymes. The project has two aims. First, Ian will identify and characterise these orthophosphate-mobilising enzymes. Second, he will investigate whether they can improve plant phosphorus uptake. Ultimately, this will provide opportunities to develop state-of-the-art sustainable agricultural practices.
Dr Lewis MacKenzie, Durham University
Usurping the scalpel: non-invasive oxygen nanosensors to refine data acquisition
Understanding how oxygen is used and consumed in the body is vital for our fundamental understanding of a wide variety of diseases (e.g. cardiovascular diseases, cancer tumours, and multiple sclerosis). However, current oxygen measurement technologies are fundamentally limited, so biomedical research often necessitates the use of lethally invasive methods, resulting in the sacrifice of laboratory animals for limited data at a single time-point.
The aim of my fellowship is to develop nanosensors capable of non-invasively measuring oxygen in cells and tissue of interest even through deep tissue (e.g. 1 – 2 cm thick). The oxygen nanosensors will be put through their paces in cells, blood, and tissue-mimicking ‘phantoms’, demonstrating that they hold the potential to non-invasively measure oxygen over extended time-periods; thereby ‘usurping the scalpel’.
This research holds the potential to not only reduce need for animal sacrifice in biomedical research, but also to make research more efficient, cheaper to fund, and more sustainable.
Dr Chiara Maniaci, Newcastle University
Regulation of protein stability by lysine hydroxylation
Cells control the rates and extent to which 'worker' proteins are produced and eliminated as a means to control physiological processes, including development and ageing. To distinguish proteins to be retained from those to be disposed of, cells use a code of alterations to proteins known as post-translational modifications (PTMs). When something goes wrong in such a complex and intricate set of processes it can lead to disease. While a number of PTMs have been characterized, many others remain to be discovered and their biological functions remain elusive. In the Fellowship, I will use a combination of biochemical, biophysical and cellular studies to shine light on an unprecedented and recently identified PTM involving atmospheric oxygen. The results will help us to understand how cells determine protein lifetimes as a function of their environment.
Dr Peter Martin, Institute of Cancer Research
Unravelling the role of topoisomerase II beta binding protein 1 (TOPBP1) in the resolution of ultra-fine anaphase bridges
Faithful and accurate division of the genome is vital to prevent damage during every cell cycle. The processes which govern chromosomal segregation are conserved throughout evolution and the accuracy of these processes is essential in complex multi-cellular organisms that rely on the cooperation between functional organs and tissues. However, cells often acquire DNA entanglements that are observed in mitosis as 'chromatin bridges', linking separating daughter cells, a sub-set of which are termed ultra-fine anaphase bridges (UFBs). If not resolved in a timely manner these bridges are a threat to the stability of the genome.
Through an interdisciplinary approach I will provide insight into the role of the multifunctional replication checkpoint protein TOPBP1 and its protein interactome in UFB resolution during mitosis. This will improve our understanding of the fundamental molecular mechanisms that facilitate the faithful transfer of genomic information to daughter cells, permitting the continuation of all multi-cellular life.
Dr Siobhan O’Brien, University of Liverpool
Exploring how species interactions shape adaptive evolution in soil microbial communities
Agricultural soil microbial communities provide vital ecosystem services such as providing nutrients to crops, protection against pathogens, breaking down toxic heavy metals and carbon storage. However, these communities are increasingly faced with harsh environmental conditions imposed by human activity – such as intensive use of pesticides, increased salinity from rising sea levels, and antibiotic run-off from pig farms. While experiments in vitro reveal that microbes can rapidly evolve resistance to such stressors, such studies tend to be limited to a single species evolving in the presence of a single stressor in a highly artificial laboratory environment. My proposed research will use real-time experimental evolution of soil microbial communities, to test if and how species interactions in complex soil microbial communities influence evolutionary responses to a stressful environment.
Dr Nuno Miguel Oliveira, University of Cambridge
Bacterial motility and chemotaxis as drivers of antimicrobial resistance in biofilms
Bacteria can actively bias their motion when exposed to chemical gradients (chemotaxis), and this behaviour is critical for their reproductive success. While we have a thorough understanding of how swimming individuals direct their motility, and indeed this is often pictured as one of the best understood biological processes, we know little about how bacteria perform chemotaxis when growing as surface-attached communities (biofilms), which is their typical growth mode in natural conditions. In particular, we do not know how biofilm bacteria control their motility when exposed to gradients of antibiotics and other antimicrobials, and this lack of understanding is surprising because bacterial biofilms are particularly resilient to antibiotic stress, and chemical gradients always emerge in biofilms. We found that biofilm bacteria actively control their motility in gradients of antibiotics, and the BBSRC Discovery Fellowship will be used to further explore this striking new bacterial behaviour. Our aim is to understand its genetic and ecological basis, and how it contributes to the evolution of antimicrobial resistance, which is a major public health concern.
Dr Irem Sepil, University of Oxford
The impact of paternal age and nutrition on offspring fitness
Mothers have long been known to influence their offspring's condition in many ways other than just transmitting genes. Less obvious is that the condition and environment of fathers can affect their sperm and, as a result, the quality of their offspring. However, we still know little about the causes and consequences of such effects. A major barrier to progress is that these effects are challenging to study in humans and other mammals. To overcome this barrier and push the field forward, I will make use of one of the major alternative models for understanding animal evolution and physiology, the fruit fly Drosophila melanogaster.
With the fruit fly, I will tackle three of the major open questions in the study of paternal effects: 1) Why do they occur? 2) How do they impact offspring? and finally 3) What causes them? I will combine large-scale evolutionary experiments with cutting-edge molecular methods, and establish a major new research program to understand all aspects of these important and fascinating effects.