Research group Epigenetics
The research group epigenetics focuses on the mechanisms that regulate human genome behaviour. These mechanisms are primarily responsible for generating cell-type specific gene expression profiles, which give rise to the large variety of cellular identities with diverse functionalities in the human body. Changes in epigenetic regulation are often at the core of pathological processes that lead to cellular dysfunctionality and result in organ malfunction and disease.
Crosstalk of proviral DNA with the human genome in chronic infection with human immunodeficiency virus (HIV)
A variety of human pathogenic viruses can enter a state of viral latency upon infection. This dormant state is thought to enable evasion from immune surveillance, permits long term persistence of the viral genome within the host cell and establishment of a chronic infection.
HIV replicates through integration of proviral DNA into the genome of infected cells. This viral life cycle has several intriguing features. Integrated proviral sequences can be transcriptionally repressed, resulting in a latently infected reservoir that is hampering current efforts to eradicate HIV once infection has occurred. Furthermore, chronically HIV-infected patients accumulate a large number of defective proviral sequences within the genomes of HIV target cells. Very little is known to date about the impact of these sequences on host cell biology.
The research project focuses on the mechanisms that govern choice of HIV integration site as well as HIV latency establishment and maintenance. Particular emphasis is put on epigenetic regulatory mechanisms. Generally we would like to understand how HIV proviral DNA integration impacts on host cell physiology.
In order to approach these questions, we employ a range of molecular biology techniques, focusing in particular on the analysis of local and genome-wide epigenetic and translational changes. We make use of site-specific targeting technologies (e.g. genome editing) in order to generate suitable cellular model systems.
Overall, we expect that our studies will promote our understanding of the biology of HIV infection and in particular of the impact of chronic infection on human host physiology. Eventually this understanding will be essential to optimize therapeutic strategies.