Project No. 2323

PRIORITY PROJECT

Primary Supervisor

Prof Gavin Foster – University of Southampton

Co-Supervisor(s)

Dr Matthew Loxham- University of Southampton

Prof Craig Storey – University of Portsmouth

Summary

Many metallic elements are critical to cellular functioning and inappropriate concentration of metals can be toxic.

Thus, regulation of cellular metal concentrations (the metallome) is critical. Studying metallomic (dys)regulation is best done with a knowledge of its spatial distribution within the target tissue and laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) based approaches have emerged at the forefront of this field. However, current approaches are constrained to discrete 2D images of a limited selection of ions, providing only a snapshot from which the 3D spatial relationships and the full metallome have to inferred. Here, the student will exploit two new technologies to develop an imaging pipeline to enable the rapid (<1 hour) generation of high resolution (<5 µm) 2D images of the full metallome (from H to U) of mm-scale biological tissues. The rapidity enables serial sections to be measured allowing 3D images to be constructed, thereby yielding new understanding of metallomic regulation, its perturbation, and its role in disease or toxicity.

In this project, a student keen to develop a multidisciplinary skillset will be supported by the supervisory team and their collaborators to:

– Develop metallomic imaging workflows, accounting for precision & accuracy and optimising sample preparation approaches to facilitate correlative imaging using other complementary modalities (e.g. SEM, immunohistology).

– Integrate 2D metallomic images of serial sections with other modalities to produce 3D maps (using open source software).

– Use the developed toolkit to study the distribution of metals in lung cells and tissue to: (1) gain new insight into the metallome of different lung cell types, (2) document metallomic perturbation in relation to lung disease, (3) study metallomic perturbation following exposure to metal-rich air pollution particles.

This project will develop a new analytical capability within the SoCoBio partnership and beyond. The initial application will provide a mechanisitic framework to understand the relationship between lung disease and air pollution.