Research


Functional Epigenome Dynamics

The Verschure group uses a synthetic, systems biology approach to understand functional epigenome dynamics.

We currently focus on:

  1. Responsiveness to epigenetic reprogramming using CRISPR/dCas (collaboration UMCG, prof. Rots)
  2. Breast cancer endocrine therapy resistance development (EU H2020 EpiPredict consortium coordinated by Verschure)
  3. UV-induced damage and repair (collaboration ErasmusMC)
  4. Age determination for forensic applications (collaboration NFI and CLHC).

Conceptual principles are tested to determine the which systems parameters lay at the basis of epigenetic plasticity and the development of particular cell subpopulations. Such cell populations can have selective advantage or unwanted behavior, enabling phenotypic diversification.

We use a combined experimental-computational approach together with epigenetic editing (CRISPR/dCas, Zinc finger-based) and development of engineered mammalian cells, to obtain cause-consequence relationships. Technologies of use are quantitative single cell biochemistry and (super)resolution microscopy, i.e. single cell RNA-seq, single molecule RNA FISH, ChIP-seq, DNAme bisulfite MPS as well as stochastic simulation and machine learning.

We use a combined experimental-computational approach together with epigenetic editing (CRISPR/dCas, Zinc finger-based) and development of engineered mammalian cells, to obtain cause-consequence relationships. Technologies of use are quantitative single cell measurements and (super)resolution microscopy, i.e. single cell RNA-seq, single molecule RNA FISH, ChIP-seq, DNAme bisulfite MPS as well as stochastic simulation and machine learning. In addition, we focus on quantitative interpretation of single cell genome-wide, measurements to explain non-trivial noise, transcription bursting and epigenetic state switching. We will consolidate our approach to map-out various mechanisms through which epigenetic transcription regulation derived heterogeneity explains cell decision-making. We will further build on our strong (inter)national collaborative network and renew funded collaborative initiatives.

Recent research highlights

► Development of a quantitative methodology (real-time, single molecule, high-throughput microscopy, genome-wide biochemical 4SUDRB-seq), to determine the genomic and epigenetic composition of genes with defined transcription dynamics, Beckman et al. BioRxiv (2020).

► Determination of the role of epigenetics for development of resistance to treatment in breast cancer cells including systematic epigenetic editing (CRISPR/dCas) to verify causality of epigenetic regulation, Gjaltema et al. Int J Mol Sci (2020), Borgoni et al. Cancers (2020), Soleimani et al. BMC Cancer (2020).

► Prof. Pernette Verschure was conference chair of the 4th International Conference on Epigenetics and Bioengineering (EpiBio) 9-11 Oct 2020 Raleigh, NC, USA (online).

► Prof. Pernette Verschure became Associate Editor being involved in launching the new Springer Nature journal Epigenetic Communications (co-journal of Clinical Epigenetics).