Ion-trap mass spectrometry for integrative biology

Lead Research Organisation: University of Cambridge
Department Name: Biochemistry

Abstract

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Technical Summary

The objectives of this proposal are to acquire high sensitivity, high throughput LCMS capabilities for metabolomics and proteomics. The principle applicants, Julian Griffin, Kathryn Lilley and Martin Welch have an established track record with respect to collaboration in systems biology projects and also with many of the co-applicants. The purchase of the requested LTQ linear ion trap mass spectrometer represents added value to existing fruitful metabolomic and proteomic studies. The proposed mass spectrometer will be situated in the newly formed Systems Biology Institute within the School of Biological Sciences in purpose built mass spectrometry laboratory facilities. The facilities within this institute will benefit the entire School of Biological Sciences at the University of Cambridge. Biochemistry has a number of on-going projects in the field of metabolomics, working on a range of organisms including plants, microbes, fruit flies, frogs and mammalian systems. This LTQ linear ion trap will provide these groups with dedicated access to a LC-MS system to increase their coverage of the metabolome. Dr Griffin¿s group will provide expertise and training in the preparation of metabolite extracts and multivariate analysis of the data obtained using the instrument. The instrument will be managed by the Cambridge Centre for Proteomics (CCP) of which Kathryn Lilley is group leader. The Cambridge Centre for Proteomics (CCP), established by funding from the BBSRC Investigating Gene Function Initiative is a state-of-the-art facility which has successfully provided proteomics expertise to the Arabidopsis and Drosophila communities. CCP has also collaborated with many laboratories within the Biochemistry Department, these collaborations attracting 7 BBSRC response mode grants over the last 18 months. The addition of a LTQ linear ion trap will greatly complement existing quadrupole time of flight mass spectrometers in this facility. CCP has two very highly skilled mass spectrmetry scientists, who would maintain the proposed LTQ instrument and be responsible for training researchers in its use. The LTQ will be maintained in the long-term as part of CCP equipment maintenance arrangements from combined access charges. The generous discount from Thermo Electron reflects the ongoing collaboration between CCP and Thermo¿s alliance partner, GE Healthcare and also the previous purchase of a GC-MS by Dr Griffin. The projects described in the proposal cover the BBSRC committee priority areas of `food metabolomics¿, `genotypic variation and responsiveness to diet¿, `diet and vascular health (DVH)¿, `from neurons to behaviour¿, `genes to physiology¿, `chemical biology¿, `integrated cellular systems in vitro¿, `post-translational modification of proteins (POPMOP)¿, `protein-ligand interactions (PROLIN)¿, `new protein technologies for difficult to analyse proteins¿, `comparative functional genomics¿, `integrating physiology¿, and `exploring the potential of metabolomics¿.
 
Description We determined that a class of drugs called ppar-delta agonists can not only increase fat burning in our muscles but also in fat tissue (white adipose tissue). This led us to further studying mechanisms involved in increasing fat burning in fat cells and we have recently published a paper describing how a simple dietary modification can increase fat burning. This may be useful anti-obesity treatments in the future.
Exploitation Route We are currently investigating these mechanisms in human intervention studies to see whether they can be rolled out for human treatments to extend healthy living.
Sectors Agriculture, Food and Drink,Pharmaceuticals and Medical Biotechnology

 
Description We have had a number of industrial collaborators use the LC-MS facilities developed for metabolomics as part of this award.
First Year Of Impact 2007
Sector Agriculture, Food and Drink,Healthcare,Pharmaceuticals and Medical Biotechnology
Impact Types Economic

 
Description Astra Zeneca CASE studentship
Amount £40,000 (GBP)
Organisation AstraZeneca 
Sector Private
Country United Kingdom
Start 10/2016 
End 09/2019
 
Description GSK-Astra Zeneca partnership awards
Amount £417,000 (GBP)
Organisation GlaxoSmithKline (GSK) 
Sector Private
Country Global
Start 04/2017 
End 03/2020
 
Description 2nd Metabolomics Sardinian Scientific School 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact 2nd Metabolomics Sardinian Scientific School was aimed at post-grad students new to the field of metabolomics. We gave seminars and workshops in various tools and techniques in metabolomics.
Year(s) Of Engagement Activity 2016
 
Description Cambridge Science Week 2017 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact took part in Cambridge Science week and put on a display on personalised medicine and health using advanced biochemical techniques.
Year(s) Of Engagement Activity 2017
 
Description Head Start science scheme for sixth form students 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact We hosted approximately thirty sixth form students for a seminar on metabolism followed by an introduction to a typical undergraduate practical class. The practical class was augmented by a practical demonstration of metabolomics where the students analyzed their own urine by high resolution 1H NMR spectroscopy and computer assisted pattern recognition to determine who was male and who was female!

We have already had a request to continue this workshop next year. A number of the students have since applied to Oxbridge despite being from schools that typically do not send students to the top universities.
Year(s) Of Engagement Activity 2011
 
Description Sardinian summer school: Metabolomics and more. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Sardinian summer school to spread the use of tools in metabolomics and lipidomics.
Year(s) Of Engagement Activity 2017
 
Description Science career advice to prospective undergraduates 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact This was a talk as part of an open day In cambridge to encourage students to study Natural sciences at Cambridge.

I received a number of requests for further information from students.
Year(s) Of Engagement Activity 2011,2012,2014
 
Description Work experience for two school boys 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Work experience for two school boys: two school boys spent a week in my lab following members around to get some experience of what its like being a scientist.
Year(s) Of Engagement Activity 2016