Opportunities

Postdoctoral research fellows

We are currently recruiting for a 3-year postdoc position:

We seek a talented individual interested in the cell biology of host-pathogen interactions to join an international team studying how bacterial endosymbionts affect the evolution of virulence in environmental fungi. This post is part of an exciting collaborative project jointly funded by the BBSRC and NSF (USA). You will join our group in Sheffield as part of an interdisciplinary consortium with parallel positions in the groups of Dr Liz Ballou in Exeter (UK) and Dr Jessie Uehling in Oregon (USA).

Recently, we found that the presence of novel endosymbiotic bacteria enables the environmental fungus Rhizopus microsporus to evade capture and killing by predatory amoebae. This consequently allows them to evade vertebrate immune cells and cause opportunistic infections (see: https://www.biorxiv.org/content/10.1101/584607v2). The overarching aim of our consortium is to determine the diversity and prevalence of bacterial endosymbionts in related fungi and understand how this effects their interactions with phagocytes and the evolution of virulence. This focus of this position in the King group is to determine how phagocyte cell biology is manipulated to evade capture, using the model amoeba Dictyostelium discoideum in combination with macrophage and zebrafish models of infection.

Advert going live any day! Application deadline will be mid-January 2022.

Independent postdoctoral research fellows

We are always interested in hearing from potential new lab members. Whilst we have no open postdoc positions currently, enquiries from competitive candidates for fellowships (EMBO/HFSP/Marie Curie etc) are strongly encouraged.

For informal enquiries please email Jason.King@Sheffield.ac.uk.

PhD studentships:

Understanding how oncogene-induced drinking drives cancer cell biology and disease

This project is currently available as part of the MRC-funded Discovery Medicine North (DiMeN) consortium. Application deadline is the 14th January 2022.

Obtaining enough nutrients to sustain their unregulated growth is essential for cancer cell survival and proliferation. A key way in which this is achieved is through scavenging and digesting extracellular proteins through a unique endocytic process called macropinocytosis (Commisso et al. 2013).

Whilst most cells don’t normally perform macropinocytosis, it is highly upregulated by activating mutations in K-Ras. These are found in 25% of all cancers, including 90% of pancreatic cancers. Blocking macropinocytosis directly reduces tumour growth in vivo, indicating therapeutic potential, but the how macropinosomes are formed and what affects this has on other cell behaviours remains unclear (Buckley and King 2017).

This 4-year PhD project will investigate how oncogenic Ras mutations cause cells to engulf extracellular proteins and how this affects turnover of the cell surface proteins that get internalised at the same time. This will be achieved using inducibly activated K-Ras cells, allowing us to turn Ras on and off at will (Matthews et al. 2020). This provides a unique opportunity to understand how this leads to extracellular protein uptake, using techniques such as cutting-edge microscopy, molecular biology and proteomics. The project will therefore provide a strong and broad training in cell biology, to identify the fundamental mechanisms of cytoskeletal regulation and endocytic trafficking required for cancer cell feeding.

This is a collaborative project between the King and Matthews groups at the University of Sheffield. This provides a friendly, inclusive, collaborative and well-funded environment with access to cutting edge facilities to undertake this work, within the broader MRC-funded PhD consortium.

We are looking for an enthusiastic candidate with at least a 2:1 degree in the biological sciences, interested in fundamental cell biological mechanisms relevant to disease.

Informal enquires are strongly encouraged, by email to Jason.king@sheffield.ac.uk

Projects for self-funded students

Understanding the role of DRAM in infection and autophagy-related disease

We are currently looking for a new student to understanding how the lysosomal protein DRAM contributes to bacterial killing and autophagy

This is a collaboration with Phil Elks at Sheffield (www.elkslab.weebly.com), and involves using both Dictyostelium and zebrafish.

The physics of phagocytosis

We are also looking for potential candidates to undertake an interdisciplinary, collaborative project with Andrew Parnell in the Department of Physics and Astronomy at Sheffield.

To effectively prevent infections, phagocytic cells of the immune system need to efficiently engulf microbes of widely varying size, shape and biomechanical properties.

How phagocytic cup formation is spatially organized, and adapts to engulfing particles of different geometries and stiffness is however poorly understood. We will directly address this, providing insight into both fundamental mechanisms of phagocytosis and immune cell function.

Objectives:

1) Analyse the mechanisms and forces used for phagocytosis of particles with differing biophysical properties

2) Understand the role of surface ligands in facilitating engulfment

3) Identify the cytoskeletal regulators that enable phagocytosis of complex shapes and differing stiffness

If this sounds interesting to you, and you think you may be able to apply for your own funding, please get in touch.