Cross-Species determinants of stress susceptibility in PSC-derived Neural Progenitors and Spinal Motor Neurons

About the project

About the Project Project Title: Cross-Species determinants of stress susceptibility in PSC-derived Neural Progenitors and Spinal Motor Neurons Life unfolds at remarkably different speeds across species, yet the molecular mechanisms that regulate developmental tempo remain poorly understood. A central unresolved question in developmental and evolutionary biology is how timing is controlled across species, with major implications for stem cell biology, regenerative medicine, and disease modelling. Emerging evidence suggests that stress responses, which vary across species and influence embryonic development, may act not only as protective mechanisms but also as active regulators of developmental timing and cellular maturation. However, it remains unknown how stress-response dynamics are integrated with developmental programs during neuronal differentiation, and how their dysregulation contributes to neurodevelopmental and neurodegenerative disease, including amyotrophic lateral sclerosis (ALS). Motor neurons provide a powerful and clinically relevant system to address this question due to their high metabolic demand, intrinsic stress sensitivity, and selective vulnerability in ALS and related disorders. Pluripotent stem cell (PSC)-derived motor neurons are widely used for disease modelling and neurotoxicity screening, but show substantial variability across species and developmental states. Whether this reflects developmental maturity, species-specific biology, or intrinsic differences in stress responsiveness remains unresolved. Building on previous work demonstrating conserved differences in motor neuron developmental tempo between mouse and human (Rayon et al., Science, 2020; Nakanoh, Stamataki et al., bioRxiv, 2025), this four-year industrial PhD project, in partnership with Axol, will establish a cross-species and disease-relevant stem cell platform to define how developmental state and species identity shape neuronal stress susceptibility, with direct relevance to ALS. Using pluripotent stem cell (PSC)-derived neural progenitor cells (NPCs) and spinal motor neurons (MNs) from multiple mammalian species, the student will investigate how stress responses emerge during neuronal differentiation and how they relate to developmental tempo, maturation, and disease-relevant vulnerability. Project aims: Develop a harmonised cross-species stem cell platform by generating spinal motor neurons from multiple mammalian PSC lines, including human and non-human primates. Define how stress susceptibility changes during neuronal development by comparing neural progenitor cells and motor neurons. Identify molecular signatures of stress resilience and vulnerability using comparative proteomic profiling. Determine how stress-response pathways influence developmental timing and neuronal maturation through targeted functional perturbations. Overall, this four-year industrial PhD project will uncover how stress biology is integrated into neural developmental programs across species, and how this integration shapes motor neuron maturation, resilience, and vulnerability in ALS. Research environment The Rayon Lab investigates the molecular and metabolic mechanisms that regulate biological timing, developmental tempo, and lifespan across species. The group combines stem cell and embryo models with quantitative experimental and computational approaches to understand how developmental processes evolve and are regulated. The project is based at the Babraham Institute and will be conducted in close collaboration with Axol, providing exposure to both academic and industrial research environments. The student will have access to state-of-the-art facilities and expertise in stem cell biology, developmental biology, imaging, genomics, proteomics, and computational analysis. Candidate profile We welcome applications from motivated students with interests in developmental biology, stem cells, neuroscience, evolution, or quantitative biology. Previous experience in cell culture, molecular biology, bioinformatics, or programming would be advantageous but is not essential, as full training will be provided. This project offers a unique opportunity to address a fundamental biological question while developing innovative stem cell technologies with direct relevance to disease modelling, drug discovery, neurotoxicity testing, and the development of more predictive preclinical models. Informal enquiries, including a brief statement of motivation, are encouraged. Please contact Teresa Rayon. Principal Supervisor Dr Teresa Rayon Email address: Teresa.rayon@babraham.ac.uk Fully funded BioSCaPe iDLA Studentship URL link to personal profile page or website: Teresa Rayon | Babraham Institute Further details about the BioSCaPe iDLA including how to apply can be found here The applications deadline for all PhD studentships: 8th December 2027 Please note interviews will be held the week commencing 18th January 2027 Students will not be able to take up an award unless they meet all University eligibility criteria and are successful in securing admission to the University. In addition, they will not be able to apply for a visa (if needed) until they hold an unconditional offer from the University. Incomplete applications will not be considered. Bioscience South Cambridge doctoral training Partnership (BioSCaPe) is a transformative PhD programme designed to create the bioscience leaders of tomorrow. Based in the heart of the world-leading Cambridgeshire bioscience cluster, BioSCaPe offers an unparalleled opportunity to combine cutting-edge research with entrepreneurial and leadership skills. BioSCaPe is a partnership between four world-leading research organisations; the Babraham Institute, Wellcome Sanger Institute, MRC Laboratory of Molecular Biology, and the University of Cambridge in collaboration with major industry partners including AstraZeneca, Illumina, Alloy Therapeutics, and others, alongside the Babraham Research Campus and its network of bioscience companies. Starting October 2027, 4-year Research Studentships will be available, leading to a University of Cambridge PhD degree, in the laboratories of Dr Jon Housley, Dr Teresa Rayon and Dr Arianne Richard at the Babraham Institute. Details of the Babraham Institute’s interactive scientific programmes can be found on www.babraham.ac.uk . As a student at the Institute, you will have access to all of the outstanding science facilities , each one providing specialist equipment and expertise to support key research techniques and technologies.

Research areas