Epigenetics and Chromatin Dynamics

Our Research

We seek to define molecular principles underpinning dynamic changes to chromatin structure during human development. We are interested in mechanistic detail: how chromatin regulatory complexes engage and modify the epigenome, and how misregulation of such processes leads to neurological disease. To this end we integrate insights from chromatin biochemistry with functional (epi)genomic methods in stem cell models of human brain development.

Aims

1. To understand how repetitive genetic elements are controlled by epigenetic mechanisms and chromatin structure.
2. To understand how these regulatory mechanisms influence transcriptional networks in healthy brain development and neurological disease.

Impact

Molecular neuroscience has mostly focused on the functions of proteins encoded by the human genome, but less than 2% of our DNA is protein-coding. Remarkably, repetitive elements (REs) comprise more than half the genome, but limitations in sequencing technologies have left REs overlooked, so-called ‘genomic dark matter’.

This is an important mechanistic blind spot: REs are highly dynamic stretches of DNA that can mobilise and duplicate themselves, and are the main source of genetic variation between human individuals. When their dynamics are not controlled, REs cause severe neurological disorders.

By researching how repetitive elements are epigenetically regulated in brain development, we will generate impacts in basic human neurobiology and urgently-needed understanding on mechanisms underpinning RE- associated neurological disorders.

List of publications from the Douse Group

Team

(name linked to profile in Lund University research portal)

Christopher Douse

Principal Investigator, christopher [dot] douse [at] med [dot] lu [dot] se (christopher[dot]douse[at]med[dot]lu[dot]se)

Caterina Francesconi

Postdoc, caterina [dot] francesconi [at] med [dot] lu [dot] se (caterina[dot]francesconi[at]med[dot]lu[dot]se)

Agnes Ong

Postdoc, agnes [dot] ong [at] med [dot] lu [dot] se (agnes[dot]ong[at]med[dot]lu[dot]se)

Ninoslav Pandiloski 

PhD student (50:50 with Jakobsson group), ninoslav [dot] pandiloski [at] med [dot] lu [dot] se

Fereshteh Dorazehi 

PhD student, fereshteh [dot] dorazehi [at] med [dot] lu [dot] se

Sylvie Tesson

Research Engineer, Sylvie [dot] Tesson [at] med [dot] lu [dot] se

Symela (Melina) Koutounidou

Project assistant, symela [dot] koutounidou [at] med [dot] lu [dot] se (symela[dot]koutounidou[at]med[dot]lu[dot]se)

Angelos Katsikas

Lab assistant, angelos [dot] katsikas [dot] 6511 [at] student [dot] lu [dot] se (angelos[dot]katsikas[dot]6511[at]student[dot]lu[dot]se)

Jana Matijevic

Masters Student

Milica Dimitrijevic

Masters Student (co-supervised by PI Nicholas Leigh)