The University of Manchester provides an environment to integrate basic, clinical and translational research for maximum societal impact.
Our researchers are world-leaders in basic and clinical research who are applying single cell approaches to enhance their research programmes.
This research is supported by state-of-the-art core research facilities containing a range of single cell analysis platforms operated by talented experimental officers.
Why single cell?
- Single cell research is becoming increasingly important to study the cellular heterogeneity found in biological systems.
- Single cell-based sequencing approaches are providing insights into the cell types found in healthy and diseased tissues in humans and during development of model organisms.
- These approaches are further augmented by studies at the protein level based on flow cytometry and mass cytometry.
- Advanced microscopy approaches coupled to fluorescent/bioluminescent markers are providing insights into how single cells behave in complex environments.
See a selection of current research projects using single cell approaches to understand disease.
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 proposed research is to decipher in real time the interactions between L. monocytogenes and host macrophages a key event in controlling infection. It builds on observation using single cell analysis and imaging showing that only a small subset of the L. monocytogenes proceeds on to establish productive infection of macrophages. This behaviour, previously undetectable in population-level analyses, raises fundamental questions about the L. monocytogenes infection strategy and underlying interactions with the host immune cells. In this project we will use 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.
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.
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.
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.
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.
Our single cell equipment is housed within our world-leading core facilities.
For single cell sequencing we have two platforms, the 10X Genomics chromium and the Takara ICELL8 system. These feed in to our comprehensive Illumina-based sequencing platforms.
We also have a CyTOF and Imaging CyTOF for multiplex analysis of protein expression in single cells in both cell populations and tissues.
For cellular analysis, we have a suite of microscopes, including 2 Zeiss LSM800 confocal systems with AiryScan detectors, and an LSM780 and LSM710, all capable of advanced fluorescence correlation spectroscopy (FCS) and Raster Image Correlation Spectroscopy (RICS) for single molecule analysis of protein quantification, dynamics and interactions.
Our specialised cameras also allow sensitive fluorescence imaging of promoter activity, in dedicated blackout rooms .
Opportunities at Manchester
We welcome new principal investigators who wish to integrate this fast-moving field into their research area.
Opportunities are available for researchers to start a research group through our Presidential Fellowship scheme.
The University has invested heavily in single cell biology, already appointing seven Presidential Fellows in our first two rounds of recruitment (Matthew Birket, Marcelo Boareto, Fong Kuan Wong, Rachel Jennings, Cerys Manning and Andreas Sagner).
We also host an internationally-competitive research programme in quantitative and biophysical biology that aims to recruit students trained in the physical sciences and train them to apply novel approaches to biological questions.
Our excellence in single cell research has been recognised by the University and has been awarded funds to work towards Institute status.
This has been further bolstered by strategic funding from the Wellcome Trust Institutional Support Fund to build and expand the research base in this area.
Find out who is working on single cell research at The University of Manchester.
Dr Bruce Humphrey
Strategic Funding Manager
Faculty of Biology, Medicine and Health
The University of Manchester
5.024 Carys Bannister Building
Tel: +44 (0)161 306 0552