Project 5 Outline: Mapping the Hidden Language of Heart Cells with Spatial Transcriptomics: Spatial Mapping of β-Adrenergic Signalling Heterogeneity in Stem Cell-Derived Cardiomyocytes
Supervisors
Dr Paolo Annibale (Physics & Astronomy) & Dr Ilary Allody (Psychology and Neuroscience)
Project description
Cardiovascular disease remains a leading cause of mortality worldwide, and β-adrenergic signalling is a central regulator of cardiac function, controlling contraction, relaxation, and adaptation to stress. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are increasingly used for disease modelling and drug testing; however, their reliability is limited by substantial cell-to-cell variability, even among genetically identical cells. Emerging evidence indicates that neighbouring cardiomyocytes can differ significantly in the molecular components governing adrenergic signalling (1), potentially leading to heterogeneous calcium handling and variable drug responses.
This project will test the hypothesis that spatially organised differences in key signalling components underlie functional heterogeneity in hiPSC-CMs. To address this, we will generate a spatially resolved, single-cell transcriptomic map of adrenergic signalling in intact cardiomyocyte monolayers.
Using established differentiation protocols, hiPSC-CMs will be cultured on gridded coverslips to preserve positional information. The student will apply targeted spatial transcriptomics to quantify four key markers representing distinct regulatory nodes: ADRB1 and ADRB2 (β₁/β₂-adrenergic receptors), PDE4B (cAMP degradation), and PRKAR1A (PKA regulatory subunit). High-resolution fluorescence imaging combined with computational segmentation will enable assignment of transcript counts to individual cells while maintaining spatial relationships (2).
Quantitative spatial analysis will identify cell-to-cell variability, detect clustering or gradients of expression, and reveal whether distinct molecular “signalling states” exist within cardiomyocyte populations. This will provide a proof-of-principle spatial atlas linking molecular heterogeneity to functional diversity.
This interdisciplinary project offers hands-on training in stem cell biology, spatial transcriptomics, advanced fluorescence imaging, and quantitative data analysis. The student will gain experience at the interface of biophysics and cardiovascular biology, preparing them for careers in academia, biotechnology, or pharmaceutical research.
Relevant References
- Bathe-Peters, Marc, et al. “Visualization of β-adrenergic receptor dynamics and differential localization in cardiomyocytes.” Proceedings of the National Academy of Sciences 118.23 (2021): e2101119118.
- Montañana-Rosell, Roser, et al. “Spinal inhibitory neurons degenerate before motor neurons and excitatory neurons in a mouse model of ALS.” Science Advances 10.22 (2024): eadk3229.
Subject area(s) and keywords
Cardiac biology, Stem cells, β-adrenergic signalling, Spatial transcriptomics, Single-cell analysis, Bioimaging, Cardiovascular physiology, Biophysics
Schools of Psychology and Neuroscience and Physics and Astronomy, University of St Andrews
The successful applicant will join a highly collaborative and interdisciplinary research environment spanning the Schools of Psychology and Neuroscience and Physics & Astronomy. This project sits at the interface of cardiovascular biology, advanced imaging, and quantitative analysis, leveraging state-of-the-art facilities and expertise in stem cell models and biophotonics. The environment provides an excellent platform for developing cross-disciplinary research skills in a vibrant and supportive setting.
Both Schools are committed to equality, diversity, and inclusion. The School of Psychology and Neuroscience and the School of Physics & Astronomy both hold an Athena Swan Silver award.
Further details and application process
This project is supported by an IBANS Research Bursary of £1000 to cover research expenses. If you are planning to apply for this project, first contact the supervisors, Dr Paolo Annibale ([email protected]) and Dr Ilary Allody ([email protected]) to discuss eligibility and obtain approval. Once an agreement is reached, you can proceed to submit your formal application.