ERC Consolidator Grants awarded to two EMBL researchers
Alba Diz-Muñoz and Arnaud Krebs from EMBL Heidelberg receive support for ambitious research projects aimed at understanding the precise regulation of crucial cellular processes
EMBL researchers Alba Diz-Muñoz and Arnaud Krebs have been awarded prestigious ERC Consolidator Grants worth 2.2 million and 2 million EUR respectively, to be used over the next five years to support ambitious projects aimed at understanding the precise regulation of crucial cellular processes. The ERC Consolidator Grants – part of the EU’s Horizon Europe programme – support independent researchers in becoming leaders in their fields.
Understanding the mechanics of cell division
Cell division is fundamental for all life forms and its dysregulation can lead to severe diseases, including cancer. Many cells must undergo dramatic shape changes in order to divide – these shape alterations are driven by dynamic mechanical processes at the cell surface. While the importance of physical cues for cell division has long been recognised, the field has been held back by the lack of specific tools that modify particular physical properties for bridging molecular and cellular scale biophysics.
The Diz-Muñoz Group at EMBL Heidelberg studies how mechanics at the cell periphery govern cell function. To address the toolset limitation, the team recently developed a new class of molecular tools that, for the first time, allows scientists to manipulate surface mechanics specifically and acutely in living cells. Using this powerful new structural biophysics approach, the team aims to systematically understand how cell surface mechanics controls the different steps of mitosis as part of the ERC-funded project MitoMeChAnics.
“Our goal is to systematically and quantitatively link cell surface architecture with the resulting mechanics and morphology, to determine the structure-function relationship at the cellular periphery in space and time during cell division,” said Diz-Muñoz. The team also plans to build data-driven theoretical models to unravel the physical principles controlling the interface between the cell membrane and the cortex (the thin layer directly underneath the membrane) and test their predictions with novel optogenetic tools.
The highly interdisciplinary project will be carried out in collaboration with the teams of Julia Mahamid and Anna Erzberger at EMBL Heidelberg.
“It is a very exciting time in the lab and this generous grant opens a new research direction,” said Diz-Muñoz. “We hope this work will open new horizons in our understanding of cell shape transitions.”
Investigating molecular mechanisms of gene regulation
Every living organism has a unique genome which contains the information necessary for survival and function. Yet, in multicellular organisms, every cell-type expresses a different set of genes, which in turn determines their activity and identity. An important question in modern biology, therefore, is to understand how a single genome can be interpreted in different ways to generate hundreds of unique gene expression patterns.
Transcription factors – a set of proteins that regulate gene expression – are key molecular regulators of this process. They control many essential cellular functions, such as the acquisition of cell identities in healthy tissues and their dysregulation in disease. Activation of a gene typically requires the cooperative binding of multiple transcription factors, which subsequently recruit various additional ‘helpers’ called cofactors. Their exact mode of action, however, remains elusive.
The Krebs group at EMBL Heidelberg combines single-cell and single-molecule genomics with large-scale genome engineering to understand fundamental mechanisms for controlling gene expression. As part of the ERC-funded project TFCoop, the team aims to create a functional classification for transcription factors and understand general rules defining their collective assembly to control gene expression. The experiments would include large-scale perturbations coupled with measures of transcription factor occupancy on single DNA molecules in vivo to gain network-level understanding of transcription factor function.
“This is essential fundamental knowledge, but it may also bring ground knowledge to several applied fields such as gene therapy,” said Krebs. “This ERC Consolidator Grant is the result of over two years of scientific planning and preparation. It acknowledges the success of my group at EMBL in bringing single-molecule genomics to the forefront of the field of gene regulation. The generous funding from ERC will allow us to study transcription factor function and their mechanisms of assembly at unprecedented scales.”
Read the full announcement by ERC about this year’s Consolidator Grants on their website.