09/11/2023
Key points:
Projects by four Institute group leaders have been successful in receiving funding through Biotechnology and Biological Sciences Research Council (BBSRC) Pioneer awards. Announced today, Pioneer awards support bold and exploratory fundamental research with the potential to transform our understanding of life.
Championing blue-skies and curiosity-driven frontier bioscience founded on scientific excellence, the awards will allow Dr Ian McGough, Dr Teresa Rayon, Dr Jon Houseley and Dr Maria Christophorou to apply revolutionary, creative and high-stakes approaches to break new ground in their respective fields.
Dr Simon Cook, Institute Director, said: “Congratulations to Ian, Teresa, Jon and Maria on these incredibly bold and visionary ideas and their success in securing Pioneer award funding to start investigating these concepts. Each of these projects combines scientific and technical expertise from across the Institute and its collaborators and I’m proud that the Institute is the perfect place to explore ideas that might potentially become transformative in each of their areas.”
Professor Guy Poppy, Interim Executive Chair at BBSRC, said: “BBSRC is committed to understanding the rules of life and by investing in cutting-edge discovery research through schemes such as the Pioneer Awards pilot, we are expanding the horizons of human knowledge while helping to unlock innovative bio-based solutions to some of the world's most pressing challenges.”
Ranging in length from 15–18 months, each of the Pioneer award projects supported at the Institute offers rapid proof-of-concepts for exciting new ideas with the potential to deliver significant insight to direct future research and even establish new research fields and therapeutic approaches.
Read UKRI’s announcement of the Pioneer awards for details of the projects supported in this round. The Institute’s four Pioneer award projects are described below.
Supporting transformational potential across cell signalling and epigenetics research
Dr Ian McGough – understanding mRNA oxidation and its role in protein aggregation and ageing
The functional decline of ageing tissues is accelerated by the formation of age-dependent protein aggregates. These protein clumps reflect the breakdown of protein quality control mechanisms acting at the protein folding, conformational fidelity and protein degradation phases, ultimately preventing normal cellular function. One theory of ageing proposes that oxidative stress is a driver of protein quality control failure.
In attempts to therapeutically prevent and counter protein aggregation, attention has focused on the proteins themselves, however cellular damage caused by oxidative stress also affects the cell’s RNA molecules. This project will investigate whether modified mRNAs interfere with general protein quality control pathways and are the origins of protein aggregates, potentially revolutionising therapeutic strategies to prevent protein aggregation.
The project will use the intestine of the fruit fly, Drosophila melanogaster, which shows age-related increases in oxidative stress and protein quality control issues. Dr Ian McGough will partner with Institute group leader Dr Della David on the project, who brings expertise in studying protein aggregation, and the team will utilise the technology and know-how in the Institute’s Mass Spectrometry, Genomics and Bioinformatics facilities.
Image: Part of a fly gut with fluorescent staining marking ubiquitin (cyan) and p62 (yellow), both of which are commonly found in disease-related protein aggregates. Cell nuclei are shown in purple.
Dr Teresa Rayon - dissecting the species-specific rates of development
A fundamental unknown in our understanding of the rules of life is how time is measured at the cellular level. This is most clearly seen during development where equivalent structures are established on different time trajectories in different species. For example, spinal cord motor neurons in humans develop in culture about 2.5 times more slowly than neurons from mice.
Building on her expertise in studying how developmental timing is controlled, Dr Teresa Rayon will use interspecies cell fusions, in this case fusing human and mouse neural progenitor cells from the equivalent developmental stage. The developmental dynamics of these hybrid cells will be analysed, including gene expression profiling, measuring protein levels and protein degradation rates, to identify key determinants of the developmental pace.
The project brings cutting-edge proteomics to classical experiments in developmental cell biology, allowing the field to move beyond correlative comparisons and reveal the fundamental molecular mechanisms that control developmental tempo. Institute experts in proteostasis from the Samant lab and technical specialists from the Institute’s Imaging, Mass Spectrometry, Flow Cytometry and Bioinformatics facilities will help deliver the project.
Image: Mouse neural progenitor cells stained with the pan neural marker SOX1 in cyan and the motor neuron progenitor marker OLIG2 in red.
Dr Jon Houseley – exploring the acquisition of drug resistance in fungi
Fungal pathogens kill over 1.5 million people per year and destroy food crops that could otherwise feed 8.5% of the global population (Bongomin & Gago et al., 2017, Fisher et al., 2012). While there’s widespread public awareness of the risk of drug-resistant ‘superbugs’ on health, fewer people are aware of the threat fungal pathogens present to health and our food supply as they develop resistance to current treatments. In 2022 the World Health Organisation (WHO) published the first-ever list of priority fungal pathogens.
Dr Houseley, an expert in how changes in the environment drive genetic change in order to ensure survival in new conditions, proposes that fungi use a rapid and reversible mechanism to confer drug resistance during exposure, which is quickly lost once the challenge subsides. The project will chart the formation and inheritance of extrachromosomal circular DNA (eccDNA) in the human pathogen Candida albicans (categorised by the WHO as a critical priority pathogen) and in the primary fungal pathogen of European wheat, Zymoseptoria tritici, to study whether eccDNA are used to ramp up the copy number of resistance-conferring genes and pass this protective status to their progeny in conditions of drug exposure.
The team will apply their developed assays for detecting eccDNA segregation to progeny cells, utilising the capability and expertise in the Institute’s Flow Cytometry, Genomics and Bioinformatics facilities and working with experts on the project’s target fungal pathogens.
Image: An illustrative representation of Candida albicans.
Dr Maria Christophorou – are extracellular histones novel messengers in cell to cell signalling?
The role of histone proteins in packaging DNA into tightly coiled condensed units within the restricted space of the cell nucleus is well defined. But what if histone proteins have a completely unappreciated signalling role, whereby they act to influence cell fate and function?
Based on the observation that histone proteins are released from stem cells maintained in culture as they transition between pluripotency states, Dr Maria Christophorou proposes that they could be fulfilling a signalling function and communicating messages between cells. The results of this project could challenge our current understanding of histone function, cell signalling and cell-cell communication.
In exploring this possibility, the Christophorou lab will apply their expertise in post-translational modification of histones to understand how histone proteins might be differentially modified to act as signalling messengers capable of influencing cell state. The Imaging facility’s state-of-the-art high-resolution microscopy and live imaging capability, and the Institute’s Mass Spectrometry capability will be key to answering this previously unexplored area. The team will work closely with Dr Nick Ktistakis who brings expertise in intracellular trafficking research to understand how histones are released from cells.
Image: Extracellular histone proteins labelled in green and DNA labelled in blue.
Press contact Dr Louisa Wood, Head of Communications, louisa.wood@babraham.ac.uk.
Image description Focal point of a light beam and the diffraction pattern when the 640nm laser of the Flow Cytometry facility’s Influx high speed flow cytometer interact with the sample stream prior to cell sorting. Entry to the Institute’s Image Prize competition 2021 by Christopher Hall, Deputy Manager of the Flow Cytometry facility.
Research funding Pioneer awards are funded by BBSRC, part of UK Research and Innovation, to support early-stage research with the potential to transform our fundamental understanding of biological systems.
Animal research statement As a publicly funded research institute, the Babraham Institute is committed to engagement and transparency in all aspects of its research. The research projects presented here use alternatives to animal models, namely cell lines, Drosophila and yeast.
Animal research is a component of our discovery research and used only when other research approaches are not suitable. Please follow the link for further details of our animal research and our animal welfare practices.
About the Babraham Institute The Babraham Institute undertakes world-class life sciences research to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. Our research focuses on cellular signalling, gene regulation and the impact of epigenetic regulation at different stages of life. By determining how the body reacts to dietary and environmental stimuli and manages microbial and viral interactions, we aim to improve wellbeing and support healthier ageing. The Institute is strategically funded by the Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation, through Institute Strategic Programme Grants and an Institute Core Capability Grant and also receives funding from other UK research councils, charitable foundations, the EU and medical charities.
About BBSRC The Biotechnology and Biological Sciences Research Council (BBSRC) is part of UK Research and Innovation, a non-departmental public body funded by a grant-in-aid from the UK government.
BBSRC invests in world-class bioscience research and training on behalf of the UK public. Our aim is to further scientific knowledge, to promote economic growth, wealth and job creation and to improve quality of life in the UK and beyond.
Funded by government, BBSRC invested £451 million in world-class bioscience in 2019-20. We support research and training in universities and strategically funded institutes. BBSRC research and the people we fund are helping society to meet major challenges, including food security, green energy and healthier, longer lives. Our investments underpin important UK economic sectors, such as farming, food, industrial biotechnology and pharmaceuticals.
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