Dr Patricija van Oosten-Hawle

Slides

Introduction

Cells employ highly conserved stress response mechanisms that mitigate the toxic consequences of protein misfolding in the face of stress and disease to maintain cellular protein homeostasis (proteostasis). New research has now established that multicellular organisms require inter-cellular communication to activate stress responses and protective protein quality control mechanisms across different tissues and organs – a process termed “transcellular chaperone signalling” or “TCS” in short.

A fundamental question in biology is to understand how these protein quality control processes, such as the expression of molecular chaperones, are communicated between cells and across tissues within the complexity of an entire organism. Our lab aims to identify and dissect the signalling components of cell nonautonomous proteostasis and how these can be harnessed to increase organismal health-span in the face of stress and disease, using C. elegans as a model system.

Current major projects

  • The tissue-specific “regulome” of transcellular chaperone signalling components
  • What is the neural circuitry that controls transcellular chaperone signalling?
  • Expanding the organismal proteostasis network at the interface between innate immune signalling and protein quality control mechanisms
  • When and where do amyloid beta aggregates really become toxic in an aging organism and how do chaperones protect against it?

 

Detailed Research Programme

Dissecting inter-tissue signalling pathways regulating organismal proteostasis

To understand the complexity of the organismal proteostasis network we use a combination of techniques including cell-type specific genomics and proteomics, conventional genetics, high-resolution imaging methods, bioinformatics as well as biochemistry and structural biology approaches. Our vision is to identify key intercellular signalling components and how they can be activated to induce protective responses in organs affected by degenerative protein (mis-) folding diseases.

Infographic showing Intestin-induced and Neuron-induced Transcellular Chaperone Signalling