Dr Rebecca McIntyre

Senior Staff Scientist

My primary interest lies in understanding how faulty genes cause human disease. I lead a team of experimental scientists that use the latest cellular, gene editing and sequencing technologies to uncover the role of genetic variants in risk for disease. My work is carried out in close collaboration with UK clinicians, statistical geneticists and bioinformaticians.

The team is currently focused on understanding the role of rare variants in risk for inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC). At present we use CRISPR/Cas9 gene editing of human primary T cells and iPS cells. Our edited iPS cells are differentiated to macrophages and intestinal organoids. We develop cellular assays and use bulk and single cell RNA-seq to better understand the biological consequences of genetic variation.

I am currently optimising methods to dissociate gut biopsies for single cell RNA-seq. The goal is to perform single cell RNA-seq on hundreds of gut biopsies from healthy individuals as well as those with Crohn’s disease. For this project I work closely with Consultant Gastroenterologist Dr Tim Raine and his team of research nurses at Addenbrooke’s Hospital. We will build eQTL maps for all cell types of the intestine and colocalise with risk loci for IBD to identify the genes and cell types that play a causal role in IBD. We will then develop HTP cellular assays to identify the cellular mechanisms and genes perturbed by the IBD risk variants, which are all required for early stage drug development.

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