Personal profile

Biography

1993
PhD in Cell Biology, University of Birmingham, UK

1993-1996
Post-Doctoral Fellow in the Department if Cell Biology, University of Geneva, Switzerland

1996-1999
Post-Doctoral Fellow at the Cancer Research UK London Research Institute, London, UK 

1999-2003
MRC Career Development Fellow in the Faculty of Life Sciences, University of Manchester, UK

2003-2008
MRC Senior Research Fellow in the Faculty of Life Sciences, University of Manchester, UK

2008-2012
Reader in the Faculty of Life Sciences, University of Manchester, UK

2012-present
Professor in the Faculty of Life Sciences, University of Manchester, UK

 

Research interests

Mechanisms of membrane traffic and how its dysregulation leads to disease

Our research is focussed on membrane traffic and how defects in this fundamental process lead to disease. Our work can be split into 3 broad areas: 1) trafficking in the secretory pathway; 2) lipid metabolism and its role in trafficking and receptor dynamics in immune cells; and 3) modelling neurological and kidney disease associated with defective lipid metabolism and trafficking in zebrafish.

1.) The secretory pathway is essential for life and responsible for the production of 30-40% of all proteins, including those secreted from cells such as collagen, antibodies, growth factors amongst numerous others. We are investigating how different cargo proteins navigate this pathway and studying the mechanisms that ensure secretory trafficking works properly, particularly at the level of the Golgi apparatus, the central organelle of the pathway. We are also interested in diseases attributed to dysregulation of secretory trafficking and are actively investigating this topic. 

2.) We are studying the mechanisms that regulate the trafficking and dynamics of key signalling receptors in immune cells. This includes how phosphoinositide lipids modulate antigen receptor dynamics in lymphocytes, both in healthy cells but also in the disease state such as in lymphoma. Additionally, we are working on the role of membrane traffic and lipid metabolism in innate immune signalling in macrophages. The aim is to understand the fundamental mechanisms at play and how they may be targeted in disease.

3.) We have generated zebrafish models of rare genetic disorders affecting the kidney, which includes Lowe syndrome, and those affecting the central nervous system, namely hereditary spastic paraplegia, a form of motor neurone disease. The disorders we are studying can be attributed to defects in lipid metabolism and membrane dynamics. We are using the zebrafish models to understand disease mechanisms, to identify new drug targets, and to screen for drugs that alleviate the disease pathology.

Overview

The cells in our body contain internal compartments, each of which performs functions that are essential for the viability of the cell and the health of the organism as a whole. The composition of these internal compartments, which are called organelles, depends upon the correct delivery of specific molecules (proteins and lipids) to them and the controlled movement of these molecules between the various organelles. This movement, referred to as membrane traffic, is also extremely important for the communication of cells with their environment, allowing the release of molecules from cells and the uptake of others into cells. Common examples of such molecules are hormones, neurotransmitters and the proteins that make up our skin and bones. Consequently, defects in membrane traffic cause many diseases in humans. Moreover, it is often exploited by pathogens to gain entry to our cells during infection. Work in the Lowe lab is aimed at identifying the cellular machinery that regulates membrane traffic, how it functions in healthy cells and how it goes awry in disease. A major goal of our work is to identify candidate molecules and pathways that are amenable to therapeutic intervention for the treatment of both human disease and pathogenic infection.

Expertise related to UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):

  • SDG 3 - Good Health and Well-being

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