17 April

Thesis defenses Charlotte Demkes and Carlo Vermeulen

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Two researchers of the Hubrecht Institute have defended their thesis successfully on April 17th. Charlotte Demkes, PhD, from the Van Rooij group, studied factors involved in heart remodeling. Carlo Vermeulen, PhD, from the De Laat group, studied interactions in the DNA that influence gene expression.

Factors involved in heart remodeling
During life, the heart has to adapt to stress situations by enlarging or stiffen. When this remodeling is permanent, this may lead to function loss and heart failure. During her PhD, Demkes researched temporary (physiological) hypertrophy in the mouse heart by studying mice after letting them swim for two weeks. She researched permanent (pathological) hypertrophy by narrowing the aorta in mice. In both cases, Demkes studied the expression in heart cells on the level of genes and microRNAs, small pieces of RNA that are able to block gene expression. In this data, she found clues for the involvement of known stress genes, but also of genes that were not previously associated with hypertrophy or heart failure. Also, Demkes researched the influence of inhibiting microRNAs on heart contractility. New factors that play a role in heart remodeling may lead to new targets for the development of heart failure therapies.

New blood test is based on differences in expression
Every cell in the human body contains the same genetic material, but DNA expression is different in each cell. This is principally determined by non-coding elements in the DNA, promotors and enhancers, that have to be in contact. Sometimes, these two elements are far away from each other, causing the DNA to fold. To gain insight in this process, the principle of Chromatin Conformation Capture (3C) was developed. 3C is a method that allows researchers to deduce promotor-enhancer interactions (proximity ligations) by treating the DNA with a fixative. 3C forms the basis for a number of similar techniques, such as MC-4C, that Vermeulen helped to develop. This technique allows the studying of interactions between longer pieces of DNA and multiple enhancers. Based on this technique, Vermeulen developed a new blood test for prenatal diagnosis.