Dr Jason King

Dr Jason King

Advanced Vice-Chancellor’s Fellow
Department of Biomedical Science
The University of Sheffield
Western Bank
Sheffield S10 2TN
United Kingdom

Room: D09 Florey building
Telephone: +44 (0) 114 222 5116
Email: Jason.King@Sheffield.ac.uk

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General

Brief career history

  • 2013-present Advanced Vice-Chancellors Fellow, University of Sheffield
  • 2007-2013 Post-doctoral fellow. CR-UK Beatson Institute. Advisor: Prof. Robert Insall
  • 2003-2007 PhD. Cardiff University. Advisor: Prof Adrian Harwood.
  • 2000-2001 MPhil(res) University of Birmingham
  • 1996-1999 BSc Medical Biochemistry, University of Birmingham

Research interests

The main focus of the laboratory is to understand how cells perform macropinocytosis – the bulk capture of extracellular fluid. This plays important and distinct roles in diverse cell types such as macrophages, dendritic cells and neurons, by allowing cells to sample their environment and regulating membrane turnover. However macropinocytosis also allows cancer cells to scavenge the extracellular nutrients required to support their growth, and provides a route for pathogens and prions to enter host cells.

The diverse importance of macropinocytosis has only recently become clear, and both the formation and maturation of macropinosomes is poorly understood. My laboratory is thus trying to answer two fundamental questions:

1) How do cells generate the cup-shaped protrusions required to entrap extracellular fluid?

2) How are macropinosomes and phagosomes processed after internalisation?

Please see our personal lab website for more information on our work

Professional activities

  • Vice-Chair Gordon Research Seminar on Autophagy in Stress, Development and Disease 2012
  • Vice Chancellor’s Advanced Fellow
  • Associate editor BMC Cell Biology
  • Society for General Microbiology, Eukaryotic Division committee member
  • Dictybase Scientific advisory board member

Full publications

Research

Autophagy and lysosomal degradation pathways

Macroautophagy is a critical process used by cells to recycle nutrients to survive starvation, but also for protein and organelle homeostasis, cellular remodelling, and protection from pathogens and mis-folded proteins. Our primary aim is to understand the underlying mechanisms of autophagic degradation, how specific targets are recruited to autophagosomes, and how this integrates into the larger cellular context.

We are also interested in mechanobiology. Previously, we discovered that autophagy is regulated by physiological levels of mechanical stress. Autophagy is critical to maintain healthy cells and tissues, and the mechanical stimulation of autophagy therefore potentially provides a novel mechanism by which tissues such as muscle, bone and cartilage can be maintained and mechanical damage repaired.

In collaboration with Cecile Perrault (Mechanical engineering), and Paul Evans (Medical School) we are now extending these studies to physiologically relevant cells and tissues. This will further our understanding of this pathway, and determine the role of mechanically-induced autophagy in cellular homeostasis.

Our primary experimental system is the soil amoeba Dictyostelium discoideum. This allows us to use powerful molecular techniques to dissect autophagy in a simple model system. In addition, as Dictyostelium exclusively use phagocytosis and macropinocytosis to take up nutrients, they are an excellent model for phagocytic immune cells. The ease with which Dictyostelium can be genetically manipulated allows us to circumvent the experimental limitations of macrophages and neutrophils, which we are currently exploiting to understand both infectious disease and fluid uptake, in collaboration with Simon Johnston.

Figure 1

Funding

  • BBSRC
  • Royal Society
Teaching

Undergraduate and postgraduate taught modules

Level 3:

  • BMS349 Extended Library Project
Opportunities

Postgraduate studentship opportunities

Host-pathogen interactions of the human fungal pathogen Cryptococcus neoformans

Co-Supervisor: Dr Simon Johnston

This project will investigate how the fungal pathogen Cryptococcus neoformans interacts with host cells (https://goo.gl/bJaQco). Cryptococcal infection is both a significant opportunistic infection that causes hundreds of thousands of deaths worldwide each year and an excellent opportunity to understand how pathogens avoid killing by the immune system.

Like many opportunistic pathogens Cryptococcus has not evolved specifically to avoid human immune cells. Rather, the normal environmental niche is soil, where its primary concern is capture by predatory amoeba. This project will therefore take a novel approach and use the amoeba Dictyostelium discoideum to investigate what happens to Cryptococcus within a physiologically revelant, model phagocytic cell. This provides an outstanding model system that allows us to genetically manipulate both the host and pathogen, and follow the transit of Cryptococcus through its host in great detail using time lapse fluorescence microscopy. This will allow the successful student to dissect how host and pathogen interact in greater detail than previously possible.

The primary aim of this study is to understand what happens to the human pathogen Cryptococcus neoformans after ingestion by phagocytic cells. This is the first line of defence in the immune system, and the ability of Cryptococcus to manipulate host phagocytes and evade digestion is the major cause of its pathogenicity (goo.gl/IkIf2V). Amazingly Cryptococcus is able to escape macrophages by a process called vomocytosis (goo.gl/BVKzL5). We have shown that Cryptococcus is also able to avoid being killed by Dictyostelium, as well as escape via vomocytosis.

This project with therefore use a combination of genetics, live cell imaging, biochemistry and flow cytometry to identify and characterize how Cryptococcus manipulates its host. This will provide a new level of understanding of cryptococcosis and identify new avenues for therapeutic intervention.

To find out more about this project and how to apply see our PhD opportunities page:

PhD Opportunities

Selected publications

Journal articles