Fibrosis (or scarring) is a common step in the majority of chronic diseases occurring in any organ. The mechanisms driving fibrosis are complex involving many different cell types. To capture the genome-wide spatial distribution of transcripts in relation to disease pathology in fibrosis, we have used spatial transcriptomics (ST) and characterized cellular heterogeneity at near single-cell resolution, while preserving spatial information. Through computational approaches, we have integrated single cell RNA and ATAC sequencing datasets to define cell type clusters and deconvolute multi-cell ST data. These studies have revealed spatial molecular signatures of scar-associated and impaired regenerative cell sub-populations associated with the pathophysiology of fibrotic disease. 

Researchers

• Professor Karen Piper Hanley
• Professor Magnus Rattray

Tissue resident immune cells within organs such as the gastrointestinal tract, lung and skin play critical roles in maintaining mammalian health, or driving chronic disease. The way in which immune cells respond to their environment or infectious challenge is dictated by transcription factors and tissue specific signals that alter the cellular programme at the level of mRNA. Using single cell technologies - such as scRNA seq - we are able to dissect the transcriptional pathways that determine whether an immune cell is inflammatory or protective in a range of tissues and clinical settings. Such advances provide us with unparalleled resolution and insights into the way the immune system functions and allows us to identify novel targets for therapeutic intervention.

Researchers

• Matt Hepworth
• John Grainger
• Joanne Konkel
• Elizabeth Mann
• Tracy Hussell
• Madhvi Menon

Listeria monocytogenes is a facultative intracellular food-borne pathogen, which is responsible for human listeriosis, an infection typified by high mortality rates (20-30%). The objective of this research is to decipher in real time the interactions between L. monocytogenes and host macrophages, a key event in controlling infectionIn this project, we are using a unique combination of single-cell biology approaches, including live-cell imaging and single cell transcriptomics to mechanistically understand how the intracellular fate of L. monocytogenes in macrophages and the infection outcome is controlled.

Researchers

• Dr Pawel Paszek
• Professor Ian Roberts
• Professor Magnus Rattray

The ability of cells to generate complex gene expression patterns is fundamental to multicellular life. While global mRNA levels can be routinely determined using ‘omics technologies, a major gap in our knowledge is how a cell produces these mRNA levels with the correct temporal dynamics. We are exploiting the rapid development and tractability of Drosophila to address how dynamic regulation of different steps in the gene expression pathway drives developmental patterning. We use live imaging approaches to visualize and model spatiotemporal gene expression dynamics at single cell resolution during embryogenesis. The effect of perturbing the dynamics on the accuracy and robustness of embryonic patterning is then determined.

Researchers

• Professor Hilary Ashe
• Professor Magnus Rattray

The outflow tract (OFT), which separates to become the aorta and pulmonary trunk, is rapidly formed and remodelled over a three-week period during human embryogenesis.

Defects arising in this process account for a third of all cases of chronic heart disease, yet little is currently known about the molecular signals orchestrating this critical event.

We are using massively parallel single nucleus RNA sequencing (snRNA-seq) and single cell assay for transposase-accessible chromatin (scATAC-seq) on cells from developing and adult hearts to define the different cell types that form the OFT and the gene regulatory networks that control their regulation.

Researchers

• Professor Nicoletta Bobola
• Professor Magnus Rattray
• Dr Simon Bamforth (Newcastle University)

This study builds on our recent findings that Barrett’s oesophagus, which is associated with progression to oesophageal adenocarcinoma, represents a reversion of normal stratified epithelium to a primitive developmental gut-like state.

We will use single cell transcriptomic and chromatin mapping techniques to compare the gene expression signatures of cells from different developmental timepoints with adult cells, and define the cell types and pathways controlling their differentiation in the upper gastrointestinal tract.

These insights will be crucial in finding a cure for what remains an aggressive and largely incurable cancer.

Researchers

• Professor Neil Hanley
• Professor Andy Sharrocks
• Professor Magnus Rattray

In recent years, our understanding of how stem cells make fate transitions has been transformed by the application of single cell technologies.

New single cell live imaging approaches are revealing the importance of protein expression dynamics, particularly pulsatile and short-period oscillatory expression of the Hes genes, on the control of cell fate.

We use single-cell live imaging in combination with mathematical modelling to explore how mechanical signals are integrated with gene expression dynamics in the developing eye.

Researcher

• Dr Cerys Manning

Professor Hilary Ashe

Professor Nancy Papalopulu

Professor Andy Sharrocks

Dr John Grainger

Professor Neil Hanley

Dr Karen Piper Hanley

Dr Matthew Hepworth

Professor Nicoletta Bobola

Dr Pawel Paszek

Professor Mike Dixon

Dr Matt Ronshaugen

Professor Judi Allen

Dr Cerys Manning

Dr Andreas Sagner

Dr Elizabeth Mann

Dr Fong-Kuan Wong

Dr Joanne Konkel

Dr Madhvi Menon

Dr Matthew Birket

Dr Rachel Jennings

Professor Tim Cootes

Dr Martin Turner

Professor Bill Lionheart

Dr Martin Fergie

Dr Syed Murtuza Baker

Professor Kody Law

Professor Magnus Rattray

Dr Mark Muldoon

Professor Oliver Jensen

Professor Korbinian Strimmer

Dr Mudassar Iqbal

Professor Tobias Galla

Professor Thomas House

Professor Sam Griffiths-Jones