Molecular mapping of SARS-CoV2 and the host response with multiomics mass spectrometry to stratify disease outcomes

Lead Research Organisation: University of Manchester
Department Name: Chemistry

Abstract

This project forms part of an international level effort to understand the mechanisms of COVID-19 disease in the global population. Despite the considerable insight gained into the virus,SARS-CoV-2, at the genetic level, the key facets of the virus structure and its pathogenic effects remain to be determined. Equally molecular descriptors that contribute to disease progression are poorly defined, and have not yet been considered in testing strategies.
Mass spectrometry (MS) can provide rapid, precise and reproducible diagnostic information at the molecular level (multiomics) that complements genomic information. In this project we will use MS to profile patient response to COVID-19 (with samples from NHS partners). This research will be exploited by our industrial project partners for diagnostic/prognostic testing protocols and for the development of vaccines and therapeutics. Research will constitute the UK effort in an international coalition initiated by the PI, COVID-19 MS, (currently over 600 members in 28 countries) who have agreed to share experience, protocols, materials and data.
This next generation measurement approach is both transferable and accessible and through replication studies involving multiple partner labs we will overcome the accuracy, sensitivity issues of current lab- based approaches while also providing population data about individual risk to COVID-19.
Our multiomics approach allows detailed structural information of the virus and its effect on the host using an intrinsic physical property - mass - unlike the indirect lab approaches currently employed.
Outputs are multifold: we will refine testing approaches, stratify treatment options, determine isolation requirements and bring much needed speed into measurement aspects of novel therapeutic development programmes - for COVID-19 and future threats.
Through our expertise in biomarker discovery and validation to profile disease mechanisms we possess the processing pipelines to extract maximum understanding from the data. As world leaders in protein structure analysis, we will structurally characterise virus:cell interactions, informing vaccine design and therapeutic intervention. Knowledge gained will be translatable to hospital testing laboratories for targeted assays, to biopharmaceutical companies for vaccine and therapeutics development, and for the development and quality control of reagents for biomarker or serological tests.
Working with LGC Ltd. diagnostics and measurement companies (Waters, Thermo, Sciex, Bruker) and through CAMS the Community for Analytical and Measurement Science major Pharmaceutical companies (Pfizer, AstraZeneca , GSK, and Allergan) we will be able to scale up our methods and translate the outcomes to provide targeted assays to the NHS for biomarkers, to validate serological tests and for vaccine and therapeutic development embedding future resilience.
The international effort is purposefully geographically spread allowing regional NHS lab access to enable rapid implementation. Finally, we established the COVID-19 MS Coalition to share sample processing protocols and to make all curated datasets open and accessible for global effort to combat this disease.

Publications

10 25 50
 
Description Impact of the COVID-19 MS Coalition The coalition has already produced more than 200 papers that use mass spectrometry to study coronavirus and there have been numerous studies exploring prognostic markers. Early COVID-19 MS Coalition studies that took place when disease rates and hospital admissions were high have contributed to a greater awareness of how to treat the virus and an understanding of how people that meet a specific criteria, such as cardiovascular problems or obesity, are affected. "Coalition members are working together to find solutions to coronavirus so it's important that we use the same methods, as we want those methods to be adopted by hospital labs," says Professor Barran. "I hope this coalition will lead to more collaborative science and that this pandemic allows us to develop public health that is less competitive. I also hope that any new resource being purchased for coronavirus, certainly through mass spectrometry, will benefit the diagnosis and treatment of other diseases." "The global data being collected now will be a great future resource as it allows scientists to have knowledge about people's health and illnesses. The way we're accelerating rapid diagnostic tests to a point of having them validated and being used by clinicians is a real celebration."
First Year Of Impact 2020
Sector Healthcare
Impact Types Cultural,Societal,Economic

 
Description COVID-19 MS coalition 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution When faced with limited access to coronavirus tests at the height of the pandemic, Perdita Barran, Professor of Mass Spectrometry at The University, was inspired to repurpose her laboratory to assist with national testing. She was not able to do that at that time. Similarly, colleagues across the UK and Europe were facing similar issues and joined forces to determine the best use of their skills and resources to support the crisis. They decided that the best use for mass spectrometry - the method of separating and weighing molecules - was to focus on prognosis, rather than diagnosis, of patients. As a result, mass spectrometry scientists looked for risk factor biomarkers to determine whether people would have a moderate or severe response to COVID-19 and the long-term effects it might have on patients. The new COVID-19 MS Coalition involves more than 800 scientists from 18 countries, including members from the Human Proteome Organisation (HUPO), an international collection of researchers who are identifying and quantifying human proteins with mass spectrometry.
Collaborator Contribution Mass spectrometry and virus detection Mass spectrometry helps scientists understand how the virus interacts with the host by investigating the nature of the viral protein and the proteins found at the back of people's throats - this practice is normally an important step when developing vaccines or therapeutics. Perdita leads the COVID-19 MS Coalition team at Manchester leading a £1.8 M grant funded by UKRI which involves five other Universities and combines the mass spectrometry capabilities of the Michael Barber Centre and the Stoller Biomarker Discovery Centre. This project is using mass spectrometry to find prognostic biomarkers to guide clinical decisions and also catalogues all mass spectrometry research data into a single web catalogue. Data scientists around the world can then access the information to see how people are affected by the disease. Perdita is also is acting as an advisor to the Department of Health and Social Care, assisting the NHS on using mass spectrometry as an alternative testing method to RT-PCR. Here the aim is to develop capacity capability for diagnostics and prognostics.
Impact We have the grant. I have been acting as the Chief scientific advisor to the DHSC for the use of Mass Spectrometry for diagnostics and prognostics.
Start Year 2020
 
Description COVID-19 MS coalition 
Organisation University of Liverpool
Country United Kingdom 
Sector Academic/University 
PI Contribution When faced with limited access to coronavirus tests at the height of the pandemic, Perdita Barran, Professor of Mass Spectrometry at The University, was inspired to repurpose her laboratory to assist with national testing. She was not able to do that at that time. Similarly, colleagues across the UK and Europe were facing similar issues and joined forces to determine the best use of their skills and resources to support the crisis. They decided that the best use for mass spectrometry - the method of separating and weighing molecules - was to focus on prognosis, rather than diagnosis, of patients. As a result, mass spectrometry scientists looked for risk factor biomarkers to determine whether people would have a moderate or severe response to COVID-19 and the long-term effects it might have on patients. The new COVID-19 MS Coalition involves more than 800 scientists from 18 countries, including members from the Human Proteome Organisation (HUPO), an international collection of researchers who are identifying and quantifying human proteins with mass spectrometry.
Collaborator Contribution Mass spectrometry and virus detection Mass spectrometry helps scientists understand how the virus interacts with the host by investigating the nature of the viral protein and the proteins found at the back of people's throats - this practice is normally an important step when developing vaccines or therapeutics. Perdita leads the COVID-19 MS Coalition team at Manchester leading a £1.8 M grant funded by UKRI which involves five other Universities and combines the mass spectrometry capabilities of the Michael Barber Centre and the Stoller Biomarker Discovery Centre. This project is using mass spectrometry to find prognostic biomarkers to guide clinical decisions and also catalogues all mass spectrometry research data into a single web catalogue. Data scientists around the world can then access the information to see how people are affected by the disease. Perdita is also is acting as an advisor to the Department of Health and Social Care, assisting the NHS on using mass spectrometry as an alternative testing method to RT-PCR. Here the aim is to develop capacity capability for diagnostics and prognostics.
Impact We have the grant. I have been acting as the Chief scientific advisor to the DHSC for the use of Mass Spectrometry for diagnostics and prognostics.
Start Year 2020
 
Description COVID-19 MS coalition 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution When faced with limited access to coronavirus tests at the height of the pandemic, Perdita Barran, Professor of Mass Spectrometry at The University, was inspired to repurpose her laboratory to assist with national testing. She was not able to do that at that time. Similarly, colleagues across the UK and Europe were facing similar issues and joined forces to determine the best use of their skills and resources to support the crisis. They decided that the best use for mass spectrometry - the method of separating and weighing molecules - was to focus on prognosis, rather than diagnosis, of patients. As a result, mass spectrometry scientists looked for risk factor biomarkers to determine whether people would have a moderate or severe response to COVID-19 and the long-term effects it might have on patients. The new COVID-19 MS Coalition involves more than 800 scientists from 18 countries, including members from the Human Proteome Organisation (HUPO), an international collection of researchers who are identifying and quantifying human proteins with mass spectrometry.
Collaborator Contribution Mass spectrometry and virus detection Mass spectrometry helps scientists understand how the virus interacts with the host by investigating the nature of the viral protein and the proteins found at the back of people's throats - this practice is normally an important step when developing vaccines or therapeutics. Perdita leads the COVID-19 MS Coalition team at Manchester leading a £1.8 M grant funded by UKRI which involves five other Universities and combines the mass spectrometry capabilities of the Michael Barber Centre and the Stoller Biomarker Discovery Centre. This project is using mass spectrometry to find prognostic biomarkers to guide clinical decisions and also catalogues all mass spectrometry research data into a single web catalogue. Data scientists around the world can then access the information to see how people are affected by the disease. Perdita is also is acting as an advisor to the Department of Health and Social Care, assisting the NHS on using mass spectrometry as an alternative testing method to RT-PCR. Here the aim is to develop capacity capability for diagnostics and prognostics.
Impact We have the grant. I have been acting as the Chief scientific advisor to the DHSC for the use of Mass Spectrometry for diagnostics and prognostics.
Start Year 2020
 
Description COVID-19 MS coalition 
Organisation University of Surrey
Country United Kingdom 
Sector Academic/University 
PI Contribution When faced with limited access to coronavirus tests at the height of the pandemic, Perdita Barran, Professor of Mass Spectrometry at The University, was inspired to repurpose her laboratory to assist with national testing. She was not able to do that at that time. Similarly, colleagues across the UK and Europe were facing similar issues and joined forces to determine the best use of their skills and resources to support the crisis. They decided that the best use for mass spectrometry - the method of separating and weighing molecules - was to focus on prognosis, rather than diagnosis, of patients. As a result, mass spectrometry scientists looked for risk factor biomarkers to determine whether people would have a moderate or severe response to COVID-19 and the long-term effects it might have on patients. The new COVID-19 MS Coalition involves more than 800 scientists from 18 countries, including members from the Human Proteome Organisation (HUPO), an international collection of researchers who are identifying and quantifying human proteins with mass spectrometry.
Collaborator Contribution Mass spectrometry and virus detection Mass spectrometry helps scientists understand how the virus interacts with the host by investigating the nature of the viral protein and the proteins found at the back of people's throats - this practice is normally an important step when developing vaccines or therapeutics. Perdita leads the COVID-19 MS Coalition team at Manchester leading a £1.8 M grant funded by UKRI which involves five other Universities and combines the mass spectrometry capabilities of the Michael Barber Centre and the Stoller Biomarker Discovery Centre. This project is using mass spectrometry to find prognostic biomarkers to guide clinical decisions and also catalogues all mass spectrometry research data into a single web catalogue. Data scientists around the world can then access the information to see how people are affected by the disease. Perdita is also is acting as an advisor to the Department of Health and Social Care, assisting the NHS on using mass spectrometry as an alternative testing method to RT-PCR. Here the aim is to develop capacity capability for diagnostics and prognostics.
Impact We have the grant. I have been acting as the Chief scientific advisor to the DHSC for the use of Mass Spectrometry for diagnostics and prognostics.
Start Year 2020
 
Description COVID-19 MS coalition 
Organisation University of Warwick
Country United Kingdom 
Sector Academic/University 
PI Contribution When faced with limited access to coronavirus tests at the height of the pandemic, Perdita Barran, Professor of Mass Spectrometry at The University, was inspired to repurpose her laboratory to assist with national testing. She was not able to do that at that time. Similarly, colleagues across the UK and Europe were facing similar issues and joined forces to determine the best use of their skills and resources to support the crisis. They decided that the best use for mass spectrometry - the method of separating and weighing molecules - was to focus on prognosis, rather than diagnosis, of patients. As a result, mass spectrometry scientists looked for risk factor biomarkers to determine whether people would have a moderate or severe response to COVID-19 and the long-term effects it might have on patients. The new COVID-19 MS Coalition involves more than 800 scientists from 18 countries, including members from the Human Proteome Organisation (HUPO), an international collection of researchers who are identifying and quantifying human proteins with mass spectrometry.
Collaborator Contribution Mass spectrometry and virus detection Mass spectrometry helps scientists understand how the virus interacts with the host by investigating the nature of the viral protein and the proteins found at the back of people's throats - this practice is normally an important step when developing vaccines or therapeutics. Perdita leads the COVID-19 MS Coalition team at Manchester leading a £1.8 M grant funded by UKRI which involves five other Universities and combines the mass spectrometry capabilities of the Michael Barber Centre and the Stoller Biomarker Discovery Centre. This project is using mass spectrometry to find prognostic biomarkers to guide clinical decisions and also catalogues all mass spectrometry research data into a single web catalogue. Data scientists around the world can then access the information to see how people are affected by the disease. Perdita is also is acting as an advisor to the Department of Health and Social Care, assisting the NHS on using mass spectrometry as an alternative testing method to RT-PCR. Here the aim is to develop capacity capability for diagnostics and prognostics.
Impact We have the grant. I have been acting as the Chief scientific advisor to the DHSC for the use of Mass Spectrometry for diagnostics and prognostics.
Start Year 2020