FWF grants awarded to Max Perutz Labs scientists

Congratulations to group leaders Roland Foisner, Martin Leeb, and Thomas Leonard who have received funding from the Austrian Science Fund FWF amounting to a total of €1,640,000. The funded projects will deal with gene regulation, cell fate decisions, and signal transduction.

Lamins are the main structural components of the eukaryotic cell nucleus, contributing to its mechanical properties. They also help organize the genome by anchoring heterochromatin. A fraction of so-called A-type lamins are found in the nuclear interior where they bind to active chromatin, influencing its mobility and accessibility. In previous work, the Foisner lab discovered that the mobility of A-type lamins and consequently chromatin depends on a protein called LAP2α. In a project driven by Postdoc Nana Neatar-Kerenyi, the team now aims to elucidate exactly how LAP2α and Lamin A influence each other. “In doing so, we aim to understand how the interaction of LAP2α and Lamin A influences chromatin accessibility to control gene regulation”.

As part of a “Weave” cross-border project Martin Leeb will collaborate with the group of Andreas Beyer, a systems biologist at the University of Cologne (Germany) to study genetic cooperation in cell identity decisions. Genetic networks that control the identities of cells during cell differentiation show a degree of redundancy. When one gene is missing, others are able to stand in and drive development and cell differentiation, allowing for robust developmental processes. The team has previously developed genetic screens to study these redundancies. “The grant enables us to cooperate with system biologists and bioinformaticians, who will help us to contextualize and analyze the data obtained from genetic screens and transcriptional analysis. With this approach, we hope to identify the key players that shape cellular identity and validate them at the molecular level,” says Martin Leeb.

3-phosphoinositide-dependent protein kinase-1 (PDK1) is an essential protein kinase that phosphorylates up to 23 downstream effector kinases, earning it the moniker of a ‘master kinase’. It controls cell growth and metabolism, and is frequently upregulated in cancer. In recent work, the Leonard lab has challenged the prevailing opinion that PDK1 is constitutively active in the cell. They could show that it relies explicitly on a membrane-embedded lipid for its activation. The lab now aims to deepen their understanding of PDK1. “We want to understand, mechanistically, the transition between the cytosolic, inactive conformation of PDK1 and the membrane-activated conformation, quantify the process at the single molecule level, and validate our in vitro findings in cells,” says group leader Thomas Leonard. “We will also explore new therapeutic opportunities in cancer treatment in collaboration with Georg Winter’s lab at the Center for Molecular Medicine.”

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