Epigenetics

Projects

The central aim of our research is to decipher epigenetic modifications and their function in neurodegenerative disorders—with a particular focus on Parkinson's disease.

Epigenetic modifications like DNA methylation and histone marks represent the nexus between the internal genetic predisposition for a disease, external influences, and phenotype (Fig. 1). Research over the past years has shown that epigenetic modifications can be influenced and—sometimes reversibly—modified by the social environment, diet, and many other external factors.

Fig 1: Schematic representation of epigenetic modifications at the nexus between environment and phenotype. Environmental factors modulate chromatin, in particular DNA methylation and histone modifications, which in turn influence gene expression and phenotype.
 

For Parkinson's disease in particular, the influence of certain environmental factors has been shown with respect to prevalence and progression of the disease. Stress, for example, can reinforce disease symptoms, whereas a stimulating environment that promotes social interactions, exercises, and cognitive challenges, can ameliorate symptoms and decelerate the disease. Yet, the underlying molecular mechanisms have remained largely unknown so far. Our group’s research is geared towards filling this knowledge gap and understanding the role of epigenetic modifications in these molecular interactions.

Specifically, with our work we are trying (i) to find the epigenetic signature—that is the characteristic modification pattern—of Parkinson's disease, and (ii) to measure the qualitative and quantitative impact of environmental factors on these epigenetic marks.

In a first step, we are using several model organisms to map DNA methylation and histone modification patterns that are characteristic for the disease. Thereby, we identify patterns in the epigenome that differ between the PD models and controls. Moreover, we expose PD and control animals to either a stimulating, stress-inducing, or ordinary environment in order to simulate certain environmental conditions and to measure their influence on epigenetic marks. We pay particular attention to epigenetic changes that occur in brain regions associated with Parkinson’s.

Once we have revealed what epigenetically differentiates PD models and controls, we will in a second step translate our findings to PD patients and study the identified regions of the (epi-)genome in humans. This will allow us to pinpoint epigenetic marks and their alterations in PD patients that may serve as biomarkers and potentially open new avenues for therapeutic treatments.