Molecular neuroscience has largely focused on the functions of protein-coding genes, which account for less than 2% of our DNA. Genomic repeats – including viral-like sequences called retrotransposons – comprise around half of the human genome, but limitations in sequencing technologies and other molecular tools have left many repeats overlooked – so-called ‘genomic dark matter’. This is an important mechanistic blind spot: repeats are dynamic stretches of DNA that can mobilise or duplicate, and impact transcriptional programs. Repeats are the main source of individual genetic variation. When their dynamics are not controlled, repeats cause severe neurological disorders.
In the Lab of Epigenetics and Chromatin Dynamics (https://www.stemcellcenter.lu.se/research-groups/douse) we are interested in how this genomic dark matter is controlled by epigenetic mechanisms during human brain development. We have a particular focus on how different protein complexes package repetitive DNA into chromatin, and how chromatin influences transcriptional dynamics. We combine chromatin biochemistry with functional (epi)genomics in human stem cell models.
In this project you will characterize how tandem and interspersed repeats shape epigenetic and transcriptomic landscapes within a defined genetic background. By employing CRISPRi and/or CRISPRa to systematically dysregulate controlling pathways, we will generate pluripotent stem cell lines that exhibit an accumulation of either retrotransposons or tandem repeats. This will facilitate a comparative analysis, offering a “magnified” view of repeat-driven effects from the parental lineage. Epigenetic, transcriptomic landscape and the ability to differentiate to the neural lineage will be investigated and compared between accumulation and parental cell lines.
Our lab is based in a dynamic, collaborative and friendly environment at BMC A11 and we have space for 1 MS student. The project would start in the autumn term but we are open to later start dates e.g. if there are additional courses that the student would like to take to prepare. We are also open to designing thesis projects that are wet-lab-only or a combination of wet and dry lab. For the latter, it would be necessary that you have at least some knowledge of how to run basic operations from a command line.
If you have any questions you are welcome to email me (Chris) directly at christopher.douse@med.lu.se – please include a brief description of why you’re interested and attach a CV, grade transcript (if available) and details of 1-2 previous supervisors or mentors who could provide a reference.
*Please be aware that we would like to have the student(s) lined up well in advance of the summer break 2026. If you are interested in starting the project earlier or during the summer, let us know.*