Target Discovery
Led by Dr Erica Bello, the Target Discovery Group focuses on enabling functional genomic screening in complex human in vitro disease models to identify clinically relevant, high-confidence targets for disease therapy.
The Target Discovery Group uses arrayed and pooled CRISPR screening methods and various target validation approaches, including CRISPR-mediated epigenome editing. They provide important input into the Functional Genomics Screening Laboratory through their expertise in gene editing and development and scaling of complex models. They also collaborate with the AI and Computational Research Group on the generation and biological interpretation of CRISPR screening and multi-omics datasets.
The team collaborates with academic researchers and clinicians in Cambridge and beyond who have expertise in specific disease areas, such as inflammatory bowel disease, and utilises physiologically relevant in vitro models. The team also contributes to training future scientists through the School of Biological Sciences MPhil programme.
Discover our Research:
Team Members
Erica Bello Head of Target Discovery Group |
 Thomas Dennison Research Associate
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 SukJun Lee Research Associate |
 Marisa Edmonds Research Assistant
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Research Collaborations
UK Human Functional Genomics Initiative: Development of CRISPR-based epigenome editing in hiPSC-derived microglia
Prof Jonathan Mill and Dr Emma Dempster, University of Exeter, and Dr Sam Washer, University of Oxford
DNA methylation plays a crucial role in regulating gene expression, and dysregulation of methylation patterns has been implicated in Alzheimer’s disease (AD), particularly affecting microglial cells – the brain’s resident immune cells. Recent epigenome-wide association studies have identified several methylation changes associated with AD pathology, with the most significant effects observed in microglia-enriched populations. This project aims to develop and optimize CRISPR-based DNA methylation editors for use in human induced pluripotent stem cell (hiPSC)-derived microglia to functionally characterize AD-associated methylation changes. By systematically testing and refining these molecular tools, we will establish an optimized platform for manipulating methylation at disease-relevant genes, providing critical insights into microglial gene regulation and identifying potential therapeutic targets for Alzheimer’s disease.
Matthias Zilbauer, Inflammatory Bowel Disease
Development of high-throughput gene editing and screening of human intestinal epithelial organoids for target ID and validation
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- Optimisation of protocols for high throughput culture of patient-derived intestinal mucosal organoids
- Development of protocols for genetic and epigenetic editing of organoids
- High content phenotyping methods
- Integration of computational research to identify key pathways/targets
Selected Publications
Lee S et al.
ClonoScreen3D-CRISPRi Uncovers Genetic Modifiers of Radiation Response in Glioblastoma
bioRxiv 2026.04.17.719014 (2026)
Bello E et al.
An Alzheimer’s disease-associated common regulatory variant in a PTK2B intron alters microglial function
iScience, 2026; 29 (2026)
Dennison T et al.
Patient derived organoid biobank identifies epigenetic dysregulation of intestinal epithelial MHC-I as a novel mechanism in severe Crohn’s Disease.
Gut 73:1464-1477 (2024)
Edgar R et al.
Culture associated DNA methylation changes impact on cellular function of human intestinal organoids.
Cellular and Molecular Gastroenterololgy and Hepatology 14(6): 1295–1310 (2022)
An organoid in the sigmoid colon, a section of the large intestine. The green colour is a stem marker called LGR5, the red is a cell membrane marker called e-cadherin, and the blue is a nuclei stain called DAPI. Video by April Foster.
An organoid in the terminal ileum, a section of the small intestine. The green colour is a stem marker called LGR5, the red a cell membrane marker called e-cadherin, and the blue is a nuclei stain called DAPI. Video by April Foster.
CRUK CAMBRIDGE CENTRE
The Milner Therapeutics Institute (MTI) is a physical affiliated research institute of the Cancer Research UK Cambridge Centre.
The MTI has three goals to help drive the development of new medicines:
- To facilitate collaborations between academic researchers and those based in the pharmaceutical industry.
- To carry out our own research focused on finding new treatments through partnership with clinicians and scientists throughout the UK.
- To enable the next generation of scientific entrepreneurs to develop new companies to deliver new treatments for disease.
These goals are aligned with the Cambridge Centre’s strategies of conducting impactful research, enabling early diagnosis, developing new leaders in cancer research and partnering with patients and the public. Through the Milner Therapeutics Consortium, we help to build teams of researchers to work together to solve challenges in cancer research. Our research teams use computational approaches and artificial intelligence to analyse information from patient samples. These data can reveal new targets to treat cancer or drug combinations that could reduce the chance of drug resistance occurring.