Research Area: Chromatin, Epigenetics and Transcriptional Regulation during Ageing
1. Research Background:
Ageing is a major risk factor for a wide range of human disorders, including cancer, cardiovascular and neurodegenerative diseases. Over the last decade, research into the process of ageing has revealed that it is astonishingly plastic, which might be exploited to approach age-related diseases from a novel angle. Many studies have focused on the genetic component of ageing, but the nongenetic regulation of ageing is recently gaining attention, specifically as profound epigenetic changes are observed. These result in alterations of gene expression, chromatin plasticity and disturbances in three-dimensional genome architecture. Importantly, changes are potentially reversible, offering opportunities to improve the ageing process itself. However, in order to design such epigenetic interventions in the future, it will be important to understand alterations in the chromatin/epigenetic landscape in molecular detail. Furthermore, research will have to address how they are integrated with the environment and impact downstream processes.
2. Research questions addresses by the group:
Research in our group largely deals with the question how chromatin plasticity is involved in transcriptional regulation. To this end, we would like to understand how i) chromatin modifications shape chromatin landscapes and allow more or less access of the transcription machinery, ii) changes in metabolism impact chromatin plasticity, as central metabolites, such as acetyl-CoA and S-adenosylmethionine are used for the modification of histones. A third, recent research direction is investigating the consequences of ageing on transcriptional and epigenetic heterogeneity and the setup of ex vivo ageing models.
3. Possible projects:
We are particularly interested in expanding our efforts in elucidating the epigenetic heterogeneity in older individuals. The main aim of this project would be the setup and validation of approaches allowing combined single-cell ATAC- and transcriptome sequencing. Subsequently, we would use the developed protocols to investigate the trajectory of heterogeneity development in ageing mouse/human tissues. One major focus would also be the question of how chromatin architecture and transcription are coordinated/coupled in the elderly.
4. Applied Methods and model organisms:
For our research we use baker’s yeast S. cerevisiae and primary and organoid cell culture. We employ a wide variety of different methodology that is dependent on the individual projects and includes state-of-the art molecular biology and biochemistry, cell culture, proteomics, metabolomics and genome engineering. All projects heavily rely on various next generation sequencing technologies and their bioinformatic analysis, e.g. ChIP-, RNA-, ATAC- and NET-seq.
5. Desirable skills and qualifications:
Applicants with a background in biology/biochemistry should have proven experience in computational techniques used in the analysis of biological data. Applicants with computational or mathematical backgrounds should demonstrate enthusiasm for biological questions and willingness to learn and perform wet-lab work. Additionally, we expect good communication skills, fluent English and the ability for teamwork.