Stoller Analytical Centre for Clinical Discovery and Diagnosis

Mass spectrometry is a highly flexible approach for analysing biological samples.

It can be used to relatively quantify hundreds to thousands of proteins within an individual sample, varying from intact tissues, purified cells to fluids. It can also be used for other activities, such as detecting changes in metabolism, and identifying drugs in metabolites.

We have a wide range of mass spectrometry equipment and we can provide expert guidance on the most appropriate experimental approach, as well as data acquisition and analysis.

More about mass spectrometry

Project examples

• Data-independent acquisition mass spectrometry in severe rheumatic heart disease (RHD) identifies a proteomic signature showing ongoing inflammation and effectively classifying RHD cases.
  
  Clinical Proteomics, 2022
  
  This study utilised mass spectrometry to screen protein expression in the plasma of 445 individuals to identify biomarkers and the dominant proteomic signatures associated with severe rheumatic heart disease.
  
  DOI: https://doi.org/10.1186/s12014-022-09345-1

• Spatially resolved phosphoproteomics reveals fibroblast growth factor receptor recycling-driven regulation of autophagy and survival.
  
  Nature Communications, 2022
  
  This study utilised combined spatially resolved and traditional phosphoproteomics, along with bioinformatics analyses and targeted assays, to define endosomal and autophagy pathways that control cell fate during disease.
  
  DOI: https://doi.org/10.1038/s41467-022-34298-2

Flow cytometry and mass cytometry technologies are highly versatile antibody-based approaches that support the analysis of up to 50 protein signatures on single cells and within formalin fixed or frozen tissue sections.

These can be used to uncover the phenotype and function of cells, and their localisation and activity in situ within healthy or diseased tissues and tumours.

We can support all phases of work from experimental and antibody panel design to data acquisition, and offer an antibody conjugation service and data analysis workflow.

More about flow cytometry

Project examples

• Longitudinal immune profiling reveals key myeloid signatures associated with COVID-19.
  
  Science Immunology, 2020.
  
  This study utilised traditional multi-parameter flow cytometry on peripheral blood mononuclear cells to assess the influence of myeloid cell populations and inflammation on the course of acute and severe COVID-19 disease.
  
  DOI: https://doi.org/10.1126/sciimmunol.abd6197

• Alterations in T and B cell function persist in convalescent COVID-19 patients.
  
  Med (NY), 2021.
  
  This study utilised flow cytometry to assess the immune cell signatures in peripheral blood mononuclear cells from individuals following recovery from COVID-19, revealing substantial differences in immune cell phenotype and function that may contribute to long COVID-19 symptoms and affect long-term immunity.
  
  DOI: https://doi.org/10.1016%2Fj.medj.2021.03.013

Light and fluorescence microscopy allows the visual investigation of biological specimens, spanning 3D reconstruction and analysis of tissues, high throughput digitisation of tissue sections, dynamic or static assessment of cellular phenotypes and functions, through to super-resolution analysis of the clustering and positioning of molecules.

All our systems are capable of imaging multiple fluorophores, providing the ability to analyse multiple components simultaneously.

We support all phases of microscopy work, including tissue processing and sectioning to prepare samples for analyses, through to providing specialised software for image analysis.

More about bioimaging

Project examples

• Human melanoma-associated mast cells display a distinct transcriptional signature characterized by an upregulation of the complement component 3 that correlates with poor prognosis.
  
  Frontiers in Immunology, 2022.
  
  This study used RNA-sequencing combined with fluorescence microscopy to assess the abundance and functional activities of melanoma-associated mast cells, determining the presence and spatial positioning of complement component 3 in mast cells within tumours.  Integrative analyses revealed that the level of complement component 3 and mast cell proteases within melanoma corresponded with poor survival. 
  
  DOI: https://doi.org/10.3389/fimmu.2022.861545

Quantitative DNA and RNA-based sequencing applications allow the interrogation of the genomic, transcriptomic and epigenomic profile and states within biological samples, and can cover whole-genome wide analyses or targeted investigations within specific genes or regions of interest (for example, exosomes or enriched/modified DNA sequences linked with disease).

The range of technologies available supports bulk tissue or cell-based investigations, single-cell analyses, and, more recently, spatial examination of frozen or FFPE tissue sections.

We provide fast, affordable and reliable services with seamless end-to-end support including advice on experimental design, sample preparation, data acquisition, and expert and bespoke bioinformatic analyses.

More about genomic technologies

Project examples

• Multiple-low-dose therapy: effective killing of high-grade serous ovarian cancer cells with ATR and CHK1 inhibitors.
  
  NAR Cancer, 2022.
  
  This study used exome and RNA sequencing approaches to describe the characteristics of ovarian cancer cell models and to evaluate novel treatment strategies for the disease.
  
  DOI: https://doi.org/10.1093%2Fnarcan%2Fzcac036

Molecular biophysics-based approaches allow investigation of interactions between proteins, small molecules and fragments, as well as the high throughput quantitation of molecule ligands.

These investigations can be performed within complex fluids such as sera and cell-culture media. Nanobody screens can also support full characterisation of target molecule biology and function.

We provide a full-service workflow including experimental design, in silico design of analytes and reagents, and data acquisition and analysis.

More about biomolecular analysis

Project examples

• Structure of PLA2R reveals presentation of the dominant membranous nephropathy epitope and an immunogenic patch.
  
  Proc Natl Acad Sci USA, 2022.
  
  This study used various peptide quantification and binding assays to characterise the specificities of autoantibodies in the sera of individuals with membranous nephropathy, and identified the dominant antibody-binding epitope in the phospholipase A2 receptor.
  
  DOI: https://doi.org/10.1073%2Fpnas.2202209119