Project Reference: TRG27-SCI-ST2

Project title: Closing the loop in human heart failure: AI-guided spatial multi-omics and perturbation for therapeutic discovery

Project outline

Heart failure remains a major challenge, with many patients progressing to end-stage disease. Yet the mechanisms needed to develop new treatments remain poorly understood. Single-cell and spatial genomics have revealed the complexity of the human heart; the next step is to translate them into therapeutic discovery.

This PhD will establish a cellular and spatial atlas of diseased hearts collected at Royal Papworth Hospital, focusing on genetic and ischaemic cardiomyopathy. Integrating single-cell and spatial genomics with clinical data will resolve disease-associated cell states and regulatory programmes across myocardium and coronary vessels. The atlas will provide the foundation for mechanistic studies.

A central aim is to connect these tissue data to experiments through an AI-agent framework embedded in the discovery process. Grounded in the human heart atlas and external biological knowledge, the agents will generate mechanistic hypotheses and identify informative experiments. Candidate mechanisms will then be tested through targeted perturbation in ex vivo tissue culture and cardiac organoids. Experimental responses will feed back into the AI framework, refining the disease model and shaping the next investigation.

The project builds on the Teichmann laboratory’s pioneering work in human single-cell and spatial genomics, including heart atlases. A 10-week rotation in the Jørgensen laboratory will provide training in vascular experimental biology and tissue culture, drawing on the group’s expertise in smooth muscle cell plasticity and vascular disease.

The PhD integrates the human disease atlas, AI framework and experimental perturbation into a single discovery system. This close integration will allow students from either wet-lab or computational backgrounds to contribute directly to the full cycle of discovery. The project will establish a new framework for AI-driven biomedical science to accelerate mechanistic understanding and therapeutic discovery.

Principal Supervisor

Professor Sarah Teichmann

Email address: sat1003@cam.ac.uk

Department / Partner Institute: Cambridge Stem Cell Institute

Website: https://www.stemcells.cam.ac.uk/people/pi/teichmann

BBSRC strategic theme

Transformative technologies