Hebrew University of Jerusalem

  • Nathke, I. (Visiting researcher)
  • Assaf Friedler (Member)

Activity: Visiting an external institution typesVisiting an external academic institution

Description

Sabbatical visit to the Hebrew University in Jerusalem working with Professor Assaf Friedler, Professor of Chemistry and Dean of the Faculty of Science.

Title
: How intrinsic disorder dictates multi-functionality of proteins in health and disease

Summary: Intrinsic disorder is emerging as a key feature in a majority of the proteome, creating a new dimension for the regulation of protein function. Numerous proteins, which are either fully or partly disordered, link key cellular signaling pathways and are aberrantly regulated in disease. The adenomatous polyposis coli (APC) protein is a prime example for a large, predominantly disordered protein at the heart of many cellular processes including Wnt signaling, cytoskeleton regulation, cell cycle regulation and more. However, very little is known about how APC chooses when, where and how to engage specific pathway(s). The temporal and spatial regulation of APC can serve as a model for how intrinsic disorder in proteins enables coordinating many pathways. The aim of our project is to combine our complementary expertise in cell biology and biochemistry of APC (Näthke) and in peptide and protein chemistry and biophysics of disordered proteins (Friedler) and initiate a joint research program that aims to determine how the intrinsically disordered regions of APC contribute to its multifaceted functions in cell biology in health and disease. This programme of work will produce novel insights into mechanisms of function of the APC protein and its regulation. In addition, it will generate novel tools for basic research with potential therapeutic and diagnostic applications. The sabbatical will allow concluding proof of concept studies to demonstrate the feasibility of the project creating the required preliminary data for a substantial funding application.

Work form the sabbatical visit was submitted for publication. It shows that the disordered domains of APC are critical for its ability to undergo liquid phase separation, which in turn regulates its function in Wnt signalling. Our findings could explain the relationship between the role of APC in Wnt signalling and its contribution to the regulation of cytoskeletal proteins, particularly microtubules. This work will be the basis for new, collaborative funding applications.
Period27 Oct 20227 Dec 2022
VisitingHebrew University of Jerusalem
Degree of RecognitionInternational