"Inflammatory Bowel Disease (IBD) affects up to 1 in 200 individuals in Europe. Current diagnosis of the two main subtypes of IBD (Crohn’s disease and ulcerative colitis) is based on endoscopy, radiology and the examination of biopsies with a high degree of uncertainty: 20% of patients are not classifiable or are rediagnosed later. The uncertainty in diagnosis extends also to medication, which is to a large degree based on trial and error. The use of molecular biomarkers could allow for an earlier and more specific diagnosis of disease type and more targeted therapy; this is the aim of my project.
My hypothesis is that differences between inflamed and non-inflamed tissue and between disease subtypes may not only be due to differential gene expression but also to alternative promoter usage, which may lead to altered protein products with modified or aberrant function. I will apply genome-wide experimental and computational methods to study differential promoter usage i) in colon tissue biopsies from IBD patients and ii) in the model system Caco-2, where we can investigate the effect of inflammation and perform functional validation of the promoters found in patients. The aim of this is to identify alternative promoters as biomarkers for diagnostics.
As one of very few research groups worldwide, my host group uses a novel technique, Cap Analysis of Gene Expression, to identify transcription start sites genome-wide, which will allow me to quantify promoter usage and to find alternative promoters. Through the project I will obtain expertise in the growing field of high-throughput sequencing analysis, while my background in bioinformatics and immunology will contribute to the success of the project. As a result, the project will provide biomarkers for diagnosis of disease subtype with the aim to make diagnosis of IBD easier and more precise, allowing for better treatment and thereby improving the quality of life for patients as well as reducing health care costs."
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