Mass spectrometry imaging of glycosaminoglycans in biological samples

Lead Research Organisation: University of Nottingham
Department Name: Sch of Pharmacy

Abstract

Glycosaminoglycans (GAGs) are chains of sugar molecules in our body that are a particularly important part of the space outside of cells. They have a number of roles including controlling how other molecules move about the body and, thus, underpin processes like virus invasion, cancer metasis, growth of tissues and organs, and the transport of nutrients from the blood supply to the rest of the body. To understand these processes researchers need tools to study GAGs, but there is currently limited tools such that reveal only a small aspect of the complex nature of these molecules. This project will use mass spectrometry imaging to simultaneously capture 1000's of different measurements that provide a full structural characterisation of GAGs. This will revolutionise the visualisation of GAGs in the same way increasing the number of colour shades in a photograph from 3 to 1000 reveals the differences and complexities that are not otherwise visible. Consider a field full of different flowers. If the field was only photographed using 3 colour shades many flowers would appear the same that were in fact different colours, and other flowers might appear of a single tone when seen with the 3 colour limit, but with 1000 colours could be seen as having mulitple tones. In the same way, differences in GAG structure currently not visible to researchers because of the limited tools available to assess the differences spatially will be made apparent by developing mass spectrometry imaging tools.

To develop an approach applicable to many national and international reseachers the project partners with three international collaborators each with different samples that have varied technical demands. Each sample set will be optimised to demonstrate the utility of the approach. These collaborations enable the analysis approach developed in this project to obtain new insights in the areas of sepsis, morphogenesis (the way that new organs form) and cancer metastasis.

Publications

10 25 50
publication icon
Du Q (2024) Targeting Macrophage Polarization for Reinstating Homeostasis following Tissue Damage. in International journal of molecular sciences

 
Description The key findings from the project so far are as follows:
We have demonstrated label free and untargeted analysis of the spatial organisation of complex sugars in various biological tissues, particularly in the brain but also in the wings from Drosophila larvae, and in tumour samples.

We have established new collaborations with six different partners partners. Knowledge exchange with collaborators at the University of Colorado has been aided through secondments involving researchers between the University of Nottingham and the University of Colorado.

We have identified changes in the type and structure of complex sugars within brain tissue after injury or sepsis. We have shown that the change in complex sugars is delayed compared to the injury event.
Exploitation Route The demonstration of label free and spatially resolved characterisation of complex sugars within different tissues has potential broad impact for allowing researchers to characterise complex sugars and their role in different diseases states. This could, in turn, highlight potential therapeutic pathways for different disease states that involve complex sugars.

The analysis on the brain has highlighted a role of complex sugars (particularly sulphated forms of chondroitin sulphate) within the physiological response to brain injury and sepsis. This understanding will underpin new developments in the treatment of these conditions. With regard to sepsis, this finding suggests a possibility to use the analysis of complex sugars as a way to more effectively diagnose sepsis.
Sectors Healthcare

Pharmaceuticals and Medical Biotechnology

 
Description Collaboration with Andrea Vortkamp 
Organisation University Duisburg-Essen
Country Germany 
Sector Academic/University 
PI Contribution We have analysed samples provided by the collaborator
Collaborator Contribution The collaborator has provided samples for analysis
Impact This is a multidisciplinary collaboration. The partner is an expert in matrix biology. We provide expertise in mass spectrometry.
Start Year 2024
 
Description Collaboration with Christian Gorzelanny 
Organisation University Medical Center Hamburg-Eppendorf
Country Germany 
Sector Hospitals 
PI Contribution We have analysed samples provided by the partner. We have presented the results as a part of progress meetings.
Collaborator Contribution The partner has provided samples for analysis and has attended progress meetings to aid in the analysis and interpretation of data.
Impact This is a multidisciplinary collaboration where the partner is an expert in matrix biology whilst we have suraface analytic and mass spectrometry expertise. The collaboration led to an unsuccessful bid to the Human Frontier Science Program entitled 'Deciphering the impact of the heparan sulfate code on the microenvironment of tumors'.
Start Year 2024
 
Description Collaboration with Ciara Shaver 
Organisation Vanderbilt University
Country United States 
Sector Academic/University 
PI Contribution We are yet to contribute to this collaboration, but intend to analyse samples provided by the partner
Collaborator Contribution The partner is providing samples for analysis
Impact This is a multidisciplinary collaboration. The partner is a clincal researcher in pulmonary disease. We are providing expertise in mass spectrometry.
Start Year 2024
 
Description Collaboration with Joseph Hippensteel 
Organisation University of Colorado
Department University of Colorado Anschutz Medical Campus
Country United States 
Sector Academic/University 
PI Contribution We have analysed a number of samples provided by the collaborator. We have presented the results to the collaborator as a part of monthly progress meetings.
Collaborator Contribution The partner has provided samples for analysis. The partner has attended monthly progress meetings and contributed to the analysis and interpretation of results.
Impact This collaboration resulted in two consecutive secondments. This is a multi-disciplinary collaboration. The collaborator is a clinical researcher specialising in sepsis and cognitive disorders. Our expertise is in the area of surface analytics and mass spectrometry.
Start Year 2024
 
Description Collaboration with Kay Grobe 
Organisation University of Münster
Country Germany 
Sector Academic/University 
PI Contribution We have analysed samples provided by the collaborator. We have analysed the results and presented at progress meetings.
Collaborator Contribution The partner as provided samples for analysis. The partner has also conducted additional experiments based upon our initial results. The partner has attended progress meetings, aiding in the analysis and interpretation of results.
Impact This is a multidisciplinary collaboration. The partner is an expert in matrix biology, whilst our own expertise is in the areas of surface analytics and mass spectrometry.
Start Year 2024
 
Description Collaboration with Kimberly Alonge 
Organisation University of Washington
Country United States 
Sector Academic/University 
PI Contribution We have analysed samples provided by the partner.
Collaborator Contribution The partner has provided samples for analysis
Impact This is a multidisciplinary collaboration, where the partner has expertise in matrix biology and we have expertise in mass spectrometry
Start Year 2024
 
Description Collaboration with Marilena Hadjidemetrious 
Organisation University of Manchester
Country United Kingdom 
Sector Academic/University 
PI Contribution We have analysed samples provided by the partner and presented the results as a part of progress meetings
Collaborator Contribution The partner has provided samples for analysis. This includes conducting additional experiments based upon initial experiments. Partner has also attended progress meetings to discuss results and contribute to the analysis and intepretation of results. The partner also gave a seminar at the University of Nottingham, which was attended by approximately 50 academics and researchers.
Impact This is a multidisciplinary partnership. The partner is an expert in nanomedicine, whilst we provide expertise in mass spectrometry.
Start Year 2024