March 31, 2020

ERC Advanced Grants for Dirk Schübeler and Nicolas Thomä

The European Research Council (ERC) has announced the recipients of this year's ERC Advanced Grants. We are delighted that two FMI group leaders are among the grantees: Dirk Schübeler will receive funding for his project "Overcoming chromatin restricted DNA access", and so will Nicolas Thomä for his project "Accessing nucleosomal DNA".

The goal of the ERC Advanced Grants is to support established, leading principal investigators to pursue a groundbreaking and high-risk project. As all ERC grants, they are in high demand and therefore very competitive. This year, of the 1881 research proposals that were submitted, 185 (9.8%) were selected for funding.

The projects submitted by Dirk Schübeler and Nicolas Thomä, two group leaders at the FMI, were both accepted for funding. It is for both of them the third time that they obtain an ERC grant. These new grants will contribute to the excellent record of the FMI, which has the highest success rate for ERC grant application of all European institutions (read more).

The successful projects by the Schübeler group and the Thomä group are both aimed at better understanding how our genes are regulated in the context of chromatin, albeit with different focuses and using different approaches. 

Essential, but challenging for binding TFs: chromatin packaging
In order to package long DNA molecules into more compact structures that can fit in the tiny nucleus of a eukaryotic cell, the DNA gets associated with proteins called histones to form chromatin. The nucleosome – made up of double-stranded DNA that loops twice around eight histones – represents the building block of chromatin packaging. But there is a problem with DNA densely packed in nucleosomes: it makes it difficult for proteins required for gene transcription to access their binding sites on the DNA.

Transcription factors (TFs) are such proteins – they regulate gene expression and govern cell identity. In chromatinised genomes, the binding sites of TFs are frequently located on nucleosomes, which severely restrict access to the DNA for the TF.

The two projects
As part of their new ERC funded-project, the Thomä group will study the exact mechanism by which TFs access nucleosomal DNA. Despite being a fundamental question in genome regulation, no detailed molecular rationale is currently available for this process. In the course of their ERC funded-project, the researchers will examine how TFs manage to engage nucleosomal DNA and how nucleosome structure and architecture is impacted by TF binding. They will use novel tools ranging from biochemistry to cryo-electron microscopy and cellular studies to generate atomic models of TFs engaging with chromatin and of enzymes that can move nucleosomes.

The Schübeler group will define in vivo the sensitivities of TFs to nucleosomes and their reliance on chromatin remodeling enzymes for binding. The researchers will characterize existing chromatin barriers and identify how TFs overcome them. This represents a crucial step towards a comprehensive understanding of the role of chromatin in gene regulation, and will advance our understanding of how specificity is generated in large eukaryotic genomes.