Dr. Patricija van Oosten-Hawle
After receiving my PhD in Molecular and Cell Biology from the Vrije Universiteit in Amsterdam, The Netherlands (2008), I joined Northwestern University (Evanston, USA) as a postdoctoral research fellow in the group of Prof. Richard I. Morimoto (2008 - 2014).
In August 2014, I joined the University of Leeds as a Lecturer in Molecular and Cell Biology.
Transcellular Chaperone Signaling in the Regulation of Organismal Proteostasis during Stress and Protein Conformational Diseases
Every cell within an organism is faced with a variety of stresses throughout its life-time, that can be potentially harmful for a functional proteome. Failure to maintain a functional proteome and thus protein homeostasis (proteostasis) leads to the accumulation of damaged proteins with devastating consequences for many essential cellular processes, resulting in tissue pathology and increased susceptibility for protein misfolding diseases (Huntington's disease, Alzheimer's disease, Parkinson's disease etc). To protect against the toxic consequences of protein misfolding, cells have evolved ancient stress response and protein quality control mechanisms allowing for the targeted induction of a network of chaperones, clearance mechanisms and signaling components.
The current knowledge and understanding of cellular stress responses and protein quality control mechanisms is however largely based on single-cell studies. In metazoans, such as the nematode C. elegans, cellular stress responses are organized coordinately between and across somatic tissues by transcellular chaperone signaling. An imbalance of proteostasis within one cell-type or tissue is sensed and signaled to other tissues to adjust chaperone levels and minimize the risk of proteotoxic damage and to promote organismal stress resistance and survival. This form of integrated stress signaling functions between cells and tissues within the organism to accommodate a dynamic proteome throughout lifespan and in response to diverse (acute and chronic) stress conditions, aging and protein misfolding diseases.
Our research aims to uncover the molecular signaling mechanisms metazoans use to coordinate induction of protective stress response mechanisms between different tissues within an organism.
Figure 1. Representation of Transcellular Chaperone Signalling. An imbalance of proteostasis in a sender tissue is sensed and recognized by adjacent and distal tissues in an organism leading to compensatory transcriptional responses, such as the heat shock response (HSR).
The model organism of C. elegans provides a powerful genetic and cell biology tool to understand how transcellular chaperone signaling is organized between a stressed "sender" tissue and responding "receiving" tissues in vivo and in real-time. We employ C. elegans models of protein conformational diseases as well as fluorescent stress response reporters to address questions on the source and nature of the "transcellular" signal, how these are transmitted and the functional and physiological consequences they induce.
PhD and MSc studentship applications
We are currently seeking applications for PhD and MSc students. We are looking for highly motivated candidates with a passion and curiosity to understand how protein homeostasis is maintained in an organism and how these mechanisms can be used to fight ageing and neurodegenerative diseases. Ideally you have some background in molecular biology, genetics and biochemistry.
Please see the link below for more information on currently available projects.
For informal enquiries please contact firstname.lastname@example.org