MASSMATTERS
Lockdown Mass Spectrometry
THOMSON MEDAL: Alison Ashcroft... p12
Jane Thomas-Oates... p18
Editor’s letter
A very warm welcome to the latest edition of Mass Matters, and a special edition for me as it is the first issue I can claim to have curated as I take over the reins of Publicity Secretary from Andy Ray. I must thank Andy for his time in that role, and for his help in getting me ready to ‘fill his boots’ – and to wish him all the best for his time in the General Secretary role! Thanks Andy ! We also pay tribute to Ashley Sage for concluded not only his time as BMSS Chair, but also bringing to a close his time on the committee, but we welcome his ongoing participation in Society matters as the Immediate Past Chair and a place on the Advisory Board.. Cheers Ash !
As with the previous edition, we have continued with our digital only distribution, and you can read some feedback we received from our members in the Your Views section. The committee believes that digital publication of Mass Matters is the direction to follow, but we are also considering ‘opt-in’ options for members who prefer a paper copy. Watch this space!
The theme of this issue reflects on the COVID-19 lockdown and how that affected our community. With a second lockdown a possibility (hopefully not though!) we hope that that some of these perspectives help teach us how to respond to the unusual times, but also to reflect on how our science has continued despite the restrictions. Thanks to all who contributed, if anyone is inspired to contribute to future editions of Mass Matters, pleas get in touch!
Best, Jon.
Jonathan Jones, BMSS Publicity Secretary
Disclaimer: Articles published in Mass Matters are not peer reviewed. Authors are solely responsible for the accuracy and content of their articles. Authors may request that final proofs of their articles are approved by the author prior to publication. If no such request is made, the editorial team will proof read the articles for spelling, grammar and general layout only. Authors must obtain any relevant permission prior to submission, including the permission of image copyright holder where applicable. The authors retain copyright to articles published in Mass Matters. All images are copyright to their respective owners. Opinions expressed in articles published in Mass Matters are solely those of the original authors and not necessarily represent those of the BMSS or its executive committee. Cover image: www.flickr.com/photos/91261194@N06/49730684207
A warm welcome to the next edition of MassMatters. As from my previous Chair’s report, I thought I had written my last but was reminded by our Publicity Secretary, Jon Jones, that I still had this last one to do!!!
2020 has certainly been a tough and unprecedented year for everyone due to the COVID-19 pandemic. As I write this, we should all be enjoying our Annual Meeting in Sheffield – enjoying the great science, networking and social activities that were in planning but that was all curtailed. The BMSS took the right decision to cancel this year’s meeting in line with Government guidance on social distancing to try and control the spread of the virus and protect everyone’s health as best possible. Running such an event is a significant undertaking for the BMSS committee, whom all do the excellent work in their spare time for free, and I’d like to personally thank all the committee for their efforts in making sure that BMSS activities continue but in a different way.
Recent committee meetings have been held virtually via Zoom conferencing to allow the Society to meet its charitable requirements in terms of Governance. SIG meetings reverted to doing things virtually from April onwards with excellent engagement and attendance from the scientific community. The Biomacromolecular Structure SIG, EFASIG, Ambient Ionisation SIG and Mass Spectrometry Imaging SIG have either held or are planning to hold virtual (and free!) webinar series as part of educational activities. The committee are also looking at the Introduction to MS Course and how to implement this as a virtual one moving forward so stay tuned for further news on this. Depending on how the pandemic unfolds and whether we get a second spike in cases, the Annual Meeting for 2021 is constantly being monitored with the hope that one day we can get back to normal with face-to-face meetings to spend time with colleagues and friends alike.
So, that’s it – over 8 enjoyable and rewarding years on the BMSS Committee has come to an end. Well - not quite as I take over as the Immediate Past Chair (IPC) on the Advisory Board replacing Gavin O’Connor. I joined in 2012 as a Ordinary Member and Trustee, moving into the Treasurer’s Exec Position, then Vice-Chair and ultimately Chair for the last 2 years. I had hoped that 2020 was going to be another good year for the BMSS especially with the planned Annual Meeting and I was really looking forward to welcoming everyone to Sheffield, but it wasn’t to be. I have thoroughly enjoyed my time serving on the BMSS committee – I’ve worked alongside some fantastic people, been part of some significant changes in the daily operation of the Society and over the last 4 or so years, seen an invigoration of a vibrant Society which is here to serve the UK Mass Spectrometry community. The Society has a bright future and is in great hands moving forward but if people reading this have ever
development as well as being able to give something back to the science of mass spectrometry you enjoy. That said, I look forward to seeing folks at future BMSS events and to celebrate with a glass of something fizzy and cold in hand. Stay tuned for more news items from the BMSS and visit the website regularly for updates. Most importantly - keep safe, healthy and happy!
All the very best!
The COVID-19 MS Coalitionaccelerating diagnostics, prognostics, and treatment
Perdita Barran on behalf of COVID-19 MS Coalition
The COVID-19 MS Coalition is a collective mass spectrometry effort that will provide molecular level information on SARS-CoV-2 in the human host and reveal pathophysiological and structural information to treat and minimise COVID-19 infection. Collaboration with colleagues at pace involves sharing of optimised methods for sample collection and data generation, processing and formatting for maximal information gain. Open datasets will enable ready access to this valuable information by the computational community to help understand antigen response mechanisms, inform vaccine development, and enable antiviral
drug design. As countries across the world increase widespread testing to confirm SARS-CoV-2 exposure and assess immunity, mass spectrometry has a significant role in fighting the disease. Through collaborative actions, and the collective efforts of the COVID-19 MS Coalition, a molecular level quantitative understanding of SARS-CoV-2 and its effect will benefit all.
In this international effort we aim to use mass spectrometry to reduce the harm caused by the SARS-Cov2 virus. We will share sample collection and processing protocols and we will share all data that is obtained to maximise the benefit for all.
The aims of the COVID-19 MS Coalition are:
• To use mass spectrometry to minimize the harm from COVID-19
• To form a coalition of mass spectrometry labs with national points of contact
• To share methods and protocols and all data
• To map the viral antigens in blood and other bio-fluids to inform serological testing
• To assay (QC) compounds produced for serological tests kits
• To develop methods to determine disease prognosis
• To use mass spectrometry to inform vaccine and therapeutic developments (mapping viral proteins and their interactions)
• To develop methods to determine the lifetime of infective particles in the environment.
Learn more of join the COVID-19 MS Coalition at http://covid19-msc.org
Ashley Sage, BMSS Chair
Ashley Sage, BMSS Chair
BMSS membership subscription
Don’t miss out, renew your BMSS membership subscription for 2021!
Don’t miss out, renew your BMSS membership subscription for 2021! You can renew quickly and easily on-line by visiting the BMSS Website, www.bmss.org.uk Why not also encourage colleagues to join the BMSS? As a member of the BMSS they will:
• Be part of a community of people with similar interests
• Have the opportunity to keep up to date with recent technological developments, learn more about MS and share knowledge and experience e.g. by joining Special Interest Groups (SIG’s)
• Be eligible to apply for grants towards small items of equipment, summer studentships and conference travel
• Be entitled to discounts for BMSS meetings
• Benefit from reduced subscription fees to the European Journal of Mass Spectrometry
• Receive copies of Mass Matters, the official publication of the BMSS, published three times a year
• Benefit from 20% off relevant book titles when purchased via Wiley Publishing (discount code required)
Students: Can benefit from our education programme by applying for travel grants, presenting research at meetings and by taking part in the Barber oral prize and Bordoli poster prize competitions. All student members also receive a general mass spectrometry text book upon joining.
New & Established spectrometrists: Can benefit from courses, careers events, links with other societies (such as ChromSoc. & RSC) and networking via the BMSS Annual Conference and Special Interest Group Meetings.
Any membership queries should be directed to:
Lisa Sage, BMSS Administrator
T: (01606) 810562
E: admin@bmss.org.uk
Lifetime Membership
An inclusive award aimed at all those who have had a sustained input into the society. Eligibility criteria:
• Respected position within the UK mass spectrometry community
• Member of BMSS for a significant amount of career
• Made notable contributions to the Society, attending and or making regular scientific contributions to BMSS sponsored meetings
• See BMSS.ORG.UK for details
Recent publications by BMSS members...
Remembering Dai Games : A Special Edition of Rapid communications in Mass Spectrometry, edited by Langley GJ. Rapid Commun. Mass Spectrom. Vol 34, Iss S4 (2020). DOI: 10.1002/rcm.8886
This Special Issue of Rapid Communications in Mass Spectrometry is dedicated to the memory and works of Professor David Edgar Games (1938–2018), Dai to all that knew him.
Dai was a pioneer of LC/MS and biomedical applications, and he served as Editor-in-Chief of Biomedical Mass Spectrometry alongside Catherine Fenselau and Michael Przybylski in the early 1980s.
This Special Issue pays homage to his works and influence in the field, highlighting the variety of applications afforded by chromatography, mass spectrometry, and allied techniques that align with Dai's research career and influence (although Dai's influence extends much further than the written words and publications contained in this issue). A born communicator, Dai was motivated by nurturing and training generations of scientists, instilling in them the desire to learn and also to network with others across the globe.
His influence and work were celebrated at the one-day meeting at Kings College London entitled; Advances in Hyphenated Mass Spectrometry, where the room was filled with friends, colleagues and former Games' research students. In
keeping with his ethos, the meeting ended with a special networking event that went on late into the evening.
Some of the articles in this Special Issue are from attendees of that meeting. It is particularly pleasing and apt that the submitting authors are generationally diverse, from Dai's peer group and also Early Career Researchers. A fitting tribute to a great, inspirational and ‘larger than life’ individual whose legacy lives on in a world where chromatography and mass spectrometry thrive.
Localization of sterols and oxysterols in mouse brain reveals distinct spatial cholesterol metabolism
Eylan Yutuc, Roberto Angelini, Mark Baumert, Natalia Mast, Irina Pikuleva, Jillian Newton, Malcolm R. Clench, David O. F. Skibinski, Owain W. Howell, Yuqin Wang, William J. Griffiths
Proceedings of the National Academy of Sciences Mar 2020, 117 (11) 5749-5760; DOI: 10.1073/ pnas.1917421117
Dysregulated cholesterol metabolism is implicated in a number of neurological disorders.
Many sterols, including cholesterol and its precursors and metabolites, are biologically active and important for proper brain function. However, spatial cholesterol metabolism in brain and the resulting sterol distributions are poorly defined. To better understand cholesterol metabolism in situ across the complex functional regions of brain, we have developed on-tissue
enzyme-assisted derivatization in combination with microliquid extraction for spot diameter with a limit of quantification of 0.01 ng/ mm2. It overcomes the limitations of previous mass spectrometry imaging techniques in analysis of low-abundance and difficult-toionize sterol molecules, allowing isomer differentiation and structure identification. Here we demonstrate the spatial distribution and quantification of multiple sterols involved in cholesterol metabolic pathways in wild-type and cholesterol 24S-hydroxylase knockout mouse brain. The technology described provides a powerful tool for future studies of spatial cholesterol metabolism in healthy and diseased tissues, surface analysis and liquid chromatography-mass spectrometry to locate sterols in tissue slices (10 µm) of mouse brain. The method provides sterolomic analysis at 400-µm
High Performance Thin-Layer Chromatography of Plant Ecdysteroids Coupled with Desorption Electrospray Ionisation–Ion Mobility–Time of Flight High Resolution Mass Spectrometry (HPTLC / DESI / IM / ToFMS). E. Claude, M. Tower, R. Lafont, I. D. Wilson & R. S. Plumb. Chromatographia (2020). DOI :10.1007/s10337-020-03917-9
The use of high performance thinlayer chromatography (HPTLC) in combination with high resolution time of flight mass spectrometry (MS) for the detection, identification and imaging (HPTLC/MSI) of ecdysteroids (insect moulting
hormones) present in a number of plant extracts obtained from members of the Silene family is demonstrated. DESI is shown to be a convenient method for the recovery of these polar polyhydroxylated steroids from the silica gel of the HPTLC plate for subsequent MS detection and imaging. The incorporation of an ion mobility separation (IMS) to the system to give HPTLC/IMS/ MS provided additional drift time data which enabled more confident identification. Using HPTLC / DESI / IMS / MS, a range of ecdysteroids were detected and characterized in extracts of S. otitis, S nutans, S. maritime, S. viridiflora and S. fimbriata.
The dietary impact of the Norman Conquest: A multiproxy archaeological investigation of Oxford, UK. Craig-Atkins E, Jervis B, Cramp L, Hammann S, Nederbragt AJ, Nicholson E, Taylor, A.R, Whelton, H., Madgwick, R. PLos ONE 15(7), DOI: 10.1371/journal. pone.0235005
This study utilises a multiproxy approach to identify changes and continuities in diet and health between the 10th and 13th centuries in Oxford. Methods comprise organic residue analysis (GC-MS, GC-C-IRMS) of ceramics, carbon (δ13C) and nitrogen (δ15N) isotope analysis of human and animal bones, incremental analysis of δ13C and δ15N from human tooth dentine and palaeopathological analysis of human skeletal remains. This revealed a broad pattern of
PAPERS: HOT OFF THE PRESS
increasing intensification and marketisation, with a much lesser and more short-term impact of the Conquest on everyday lifestyles than is suggested by documentary sources.
Anion-exchange chromatography mass spectrometry provides extensive coverage of primary metabolic pathways revealing altered metabolism in IDH1 mutant cells. Walsby-Tickle, J., Gannon, J., Hvinden, I. et al Commun. Biol. 3, 247 (2020). DOI: 10.1038/s42003-020-0957-6
Altered central carbon metabolism is a hallmark of many diseases including diabetes, obesity, heart disease and cancer.
Identifying metabolic changes will open opportunities for better understanding aetiological processes and identifying new diagnostic, prognostic, and therapeutic targets. Comprehensive and robust analysis of primary metabolic pathways in cells, tissues and bio-fluids, remains technically challenging. We report on the development and validation of a highly reproducible and robust untargeted method using anion-exchange tandem mass spectrometry (IC-MS) that enables analysis of 431 metabolites, providing detailed coverage of central carbon metabolism. We apply the method in an untargeted, discovery-driven workflow to investigate the metabolic effects of isocitrate dehydrogenase 1 (IDH1) mutations in glioblastoma cells. IC-MS provides comprehensive coverage of central metabolic pathways revealing significant elevation of 2-hydroxyglutarate and depletion of 2-oxoglutarate. Further analysis of the data reveals depletion in additional metabolites including previously unrecognised changes in lysine and tryptophan metabolism.
Hot-stage microscopy – Direct Analysis in Real-time mass spectrometry (HDM) as a novel tool for monitoring thermallydriven reactions on a small scale.
Ashton G.P., Harding L.P., Midgley G., Parkes G.M.B. Analytica Chimica Acta 2020, 1128, pp.129-139. DOI: 10.1016/j.aca.2020.06.059
An instrumental combination of hot-stage microscopy and DART-MS (HDM) has been used to profile in-situ small scale organic reactions. Both homogenous and heterogenous state reactions were thermally driven without the need for solvents in a ‘green chemistry’ approach. Ion profiles of reactants, transient intermediates, products and by-products have been assigned, correlating well with colour measurements and the reactions’ physical appearance.
Urine steroid metabolomics for the differential diagnosis of adrenal incidentalomas in the EURINEACT study: a prospective test validation study. Bancos I, Taylor AE et al Lancet Diabetes Endocrinol 2020, July 23, 2020. DOI: 10.1016/ S2213-8587(20)30218-7
Urine steroid metabolomics is the combination of mass spectrometry-based urinary steroid metabolite profiling and machinelearning-based data analysis. In a retrospective proof-of-principle study, we showed that this approach was highly promising for the detection of ACC, with high sensitivity and specificity. In this prospective, multicentre, test validation study, we assessed the diagnostic accuracy of urine steroid metabolomics for the detection of ACC in patients with newly diagnosed adrenal masses compared with routinely employed imaging strategies.
Laser ablation inductively coupled plasma mass spectrometry as a Novel Clinical Imaging Tool to Detect Asbestos Fibres in Malignant Mesothelioma Rapid communications in mass spectrometry. O.M. Voloaca, C.J. Greenhalgh, L.M. Cole, M.R. Clench, A.J. Managh, S.L. Haywood-Small. 2020. DOI: 10.1002/rcm.8906
Malignant pleural mesothelioma is an extremely aggressive and incurable malignancy associated with prior exposure to asbestos fibres. Difficulties remain in relation to early diagnosis, notably due to impeded identification of asbestos in lung tissue. This study describes a novel laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging approach to identify asbestos within mesothelioma models with clinical significance.”
Needles in haystacks: using fast-response LA chambers and ICP-TOF-MS to identify asbestos fibres in malignant mesothelioma models Journal of analytical atomic spectrometry. C.J. Greenhalgh, O.M. Voloaca, P. Shaw, A. Donard, L.M. Cole, M.R. Clench, A.J. Managh, S.L. Haywood-Small. 2020. DOI: 10.1039/D0JA00268B.
This article presents a laser ablationinductively coupled plasma-mass spectrometry (LA-ICP-MS) method to identify asbestos fibres in cellular models of mesothelioma. Use of high-speed laser ablation system enabled rapid imaging of the samples with a lateral resolution of 3 µm, whilst use of a prototype time-of-flight ICP-MS provided pseudo-simultaneous detection of the elements between mass 23 (Na) and mass 238 (U).
Visualisation tools for dependent peptide searches to support the exploration of in vitro protein modifications. Preston GW, Yang L, Phillips DH, Maier CS PLOS ONE 15(7): e0235263, 2020. DOI: 10.1371/journal.pone.0235263
Dependent peptide searching is a method for finding modified peptides in LC-MS/MS data from bottom-up proteomics analyses. In this paper, we present a set of visualisation tools (R scripts) with which to explore dependent-peptide search results (MaxQuant output files). We describe the use of the tools for characterising proteins that have been modified by reactive small molecules in vitro.
Using mass spectrometry to transform the assessment of sexual assault evidence. Stephanie Rankin-Turner, Paul F. Kelly, Roberto S. P. King, James C. Reynolds. Forensic Chemistry, Vol 20, August 2020, 100262. DOI: 10.1016/j. forc.2020.100262
Sheath-flow probe electrospray ionisation mass spectrometry has been applied to the in situ analysis of sexual assault evidence. Fresh and aged semen samples were directly analysed, demonstrating the detection of compounds that could be used to quickly confirm the presence of semen in a forensic investigation. This ambient ionisation technique has an analysis time of less than 10 seconds per sample, and could replace the non-specific, destructive semen presumptive tests currently used.
Focus on diversity & inclusion
2020 has been a year of many challenges, but the issues facing Diversity and inclusion were brought into sharp focus and we asked our Equality, Diversity & Inclusion (EDI) sub-committee to give some insights on how the BMSS is taking steps to combat challenges in this area.
The BMSS EDI sub-committee was formed in September 2019 with a remit to systematically understand and calibrate the current practice of equality, diversity and inclusion within our Society. The EDI subcommittee aims to develop robust metrics for the assessment of equality, diversity and inclusion across the Society’s activities. The EDI subcommittee will take the lead in developing targeted actions to address any areas of concern identified from its on-going internal auditing processes.
Our first task was to prepare our terms of reference and our webpage! We strongly encourage you, the BMSS community, to engage with us and we welcome your ideas on additional information you would like to see on our webpage. We also like to hear about any events you would like to see promoted on the website and any links to external groups you would find useful to find on the webpage please contact one us using the details below so that we can work with you to promote positive initiatives.
New Initiatives
The first new initiative of the EDI sub-committee was championing the adoption of the BMSS Carers Support Fund which was launched at the beginning of this year. The Society introduced the BMSS Carers Support Fund to facilitate attendance at scientific events, including but not limited to BMSS meetings, by our members with any caring commitments. This pilot programme was allocated a modest
budget for 2020 and will assist us to better understand, through interaction with applicants, the needs of our community with caring responsibilities, and gauge the funding horizon for future iterations of this programme.
New Procedures
We recognise that it is important to understand the people we represent better, with this in mind we have designed an anonymous EDI Questionnaire that will be available to all participants at all future BMSS events (SIG meetings and the annual meeting). This is ready to be introduced at the first in-person event that can go ahead after the COVID-19 pandemic. We are also exploring alternative options for EDI monitoring in the shorter term. It is our hope that EDI monitoring in this way will provide an opportunity for anonymous data gathering that will help the BMSS committee to understand who we represent and identify key areas in which new initiatives and policies are required to improve the BMSS experience for everyone.
The EDI sub-committee have also produced a set of guidelines for event organisers to promote inclusivity for all participants at our events. These new resources are available to all event organisers and have been distributed via the SIG co-ordinator. You may have read an article in the last edition of Mass Matters that highlighted inclusivity considerations surrounding colour selections for presentation slides to offer inclusivity for colour blind participants.
New Events
At the annual BMSS conference in 2019 we held the first LGBT+ social event. This event was held at the specific request of one of our members in response to a highlighted desire for a dedicated social event. This event was
positively received and will become a regular part of the annual conference social programme. We planned to run the second LGBT+ social event at the 2020 annual conference, with adjustments to the timing and setting to reflect the feedback from attendees of the 2019 event. If you have ideas about other social or similar events you feel you would benefit from in the annual event programme that the EDI subcommittee could organise or support the organisation of we would welcome your suggestions and we’re keen to facilitate this.
New Committee Member
We actively encourage members to engage with the EDI sub-committee and are keen to welcome new members to improve diversity in our representation and increase our capacity. We have recently welcomed Jingshu to the EDI subcommittee. Jingshu grew up in Asia and received tertiary education in New Zealand. She came to UK as a postdoc and currently works at AstraZeneca as a senior scientist in mass spectrometry. She is the EDI’s first member representing mass spectrometrists in industry.
Contact Us
The BMSS EDI sub-committee proactively invites substantive interaction with members who wish
to engage with our EDI journeyplease don’t hesitate to reach out to us. We are keen to hear your ideas for improving EDI in the society and to hear about your experiences. We also welcome additional volunteers on the EDI sub-committee, if you would like to find out more about how you can get involved please do not hesitate to contact us.
The EDI sub committee are:
Dr Rian Griffiths, University of Nottingham, rian.griffiths@ nottingham.ac.uk
Dr Lindsay Harding, University of Huddersfield, l.p.harding@hud.ac.uk
Mr Rhodri Owen, Swansea University, r.n.owen@swansea.ac.uk
Dr Jingshu Xu, Astra Zeneca, jingshu.xu@astrazeneca.com
Virtual MSIS OurCon MS Imaging Seminars
The Mass Spectrometry Imaging Society & BMSS Partner to Deliver a Virtual Seminar Series this Autumn
Mark A. McDowall
BMSS Meetings Secretary
The COVID-19 pandemic has necessitated the cancelation of many international and national events. The BMSS was forced to cancel its Annual Meeting (BMSS41) and several affiliated Special Interest Group (SIG) events. This has significantly constrained ‘analogue’ dissemination of new developments in Mass Spectrometry, limited the opportunity for Early Career Researchers to share their work & develop their professional profiles, and frustrated community networking generally.
The BMSS Imaging Mass Spectrometry SIG championed by Professor Malcolm Clench (SHU) scheduled its annual 1-day event for May 2020, unfortunately that had to be cancelled as a result of COVID-19. Dr Peter Marshall (GSK, UK) subsequently proposed a virtual series of events as an alternative. Peter’s suggestion lead to a productive conversation with Professor Liam McDonnall (Leiden University), President of the Mass Spectrometry Imaging Society (MSIS) based in Europe. The BMSS have now formed a partnership
with the MSIS. The two Societies are co-delivering a series of virtual MS Imaging seminars over the summer and autumn (2020). Our initial bilateral discussion with the MSIS has evolved into a wider alliance supported by multiple national Mass Spectrometry societies, IMSF and the Imaging Mass Spectrometry Society (IMSS) based in the USA.
We look forward to working with Liam, MSIS & IMSS colleagues, and affiliated MS society members this year. Please visit the Virtual Mass Spectrometry Imaging Seminars event page on the BMSS website to register for your ZOOM meeting invitation, free of charge, and submit an abstract on-line (if you so wish).
Virtual Mass Spectrometry Imaging Seminars 2020: www.bmss.org.uk/virtual-msisourcon-ms-imaging-seminars-2020/
The Mass Spectrometry Imaging Society (EU): www.ms-imaging.org
The Imaging Mass Spectrometry Society (USA): www.imagingmssociety.org
The emotional impact of lockdown
Certified Professional Coach working with Life Science Professionals to redefine how we “do” work, and Business Development Manager of Genedata, a Swiss based provider of MS software solutions.
In our pursuits to be successful we often find ourselves juggling all of our responsibilities with only a set 24 hours in a day. The inability to add more hours to a day makes it imperative that we learn to manage our time and find ways to carve out time for ourselves, so we can achieve our goals sustainably – to flourish and thrive, rather than just survive! This has never been more true than in 2020 with the restrictions placed upon many of us due to the (unfortunately on-going) COVID-19 situation. Overnight we have had to relearn and readdress the balance in our lives in order to simply make sense of this new world we live in. I have found that the adage of ‘healthy-body, healthy-mind’ is true, but considered in reverse. In managing my own time since Lockdown 1.0 I found that implementing structure gave me a sense of stability in a sea of change.
Remaining Focused
Many of us over the course of the past few months have experienced “brain fog” and the inability to focus on what needs to be done. Those days when the to-do list never seems to get any shorter, when we are easily distracted and procrastinate like crazy, clock watching until we can log-off and then feeling guilty and frustrated that we “just can’t focus.” On days
like this know that you are not alone in experiencing this phenomenon. We are currently in unprecedented times, our way of living and working has been turned on its head. We now have to “sweat the little things” like the rigmarole of the weekly shop with mask, kids, hand sanitiser at the ready, or how to set up the webcam for the virtual meeting with a key client or your boss when the backdrop behind you looks like a bomb has hit it. It is not surprising therefore that with all those “little” things occupying valuable brain space, that we occasionally struggle to focus. That said there are things that we can do to help our ourselves.
1. Remember the “Bigger Picture” 2. Download, Delete, Delegate, Do 3. Be SMART
4. Reward yourself and recognise your achievements
5. Be firm with your boundaries
6. Make use of tools
7. Move your body
When we are caught up in our dayto-day reality, it can be difficult to remember why we are doing what we are doing. Take time to reconnect with your “why” and what is important to you. Think about your personal values, your vision for yourself, your personal mission statement. Take time to mentally connect your daily activities to where they fit into this “Bigger Picture”. This will help you spend more time focussed on the things which will make a real difference.
That said when we look at the Big Picture we can sometimes get overwhelmed with all of the steps involved in achieving a goal. This is where “Download, Delete, Delegate, Do” comes in. Get everything out of your head and onto paper, including all those little tasks that have been there forever, but you haven’t managed to do; break the big picture goal down into systematic, manageable baby steps. Now looking at everything
on the piece of paper go through them all and delete any which are no longer relevant, not needed –be ruthless! Once you have your slimmed down list look to see where you could ask for help or delegate the task to someone else. Now you have your final list and before you start to “Do” there is one final step – prioritisation. Rank all the items according to their importance/ urgency – which ones Absolutely (A) have to be done today, which ones would it be Brilliant (B) if they got done today and which ones Could (C) wait to tomorrow. Or find your own way of organising your daily activities that works for you for example, use stars, arrows, numbers etc.
Now you have prioritised the tasks are they manageable in the time available? This is where you have to “Be SMART” and determine what is realistic. Is there an interim step or a holding email that can go out and buy you a couple of days more? But don’t be tempted to leave the most painful task for last, think instead how pleased and relieved you’ll be when it’s complete!
Find some time at the end of the day or week to recognise what you have achieved and to acknowledge the projects you have moved forward (no matter how small those steps forward were). Give yourself a pat on the back. This simple reflection process is an important circuit break. It is so easy to tick done and move onto the next thing, racing through the day, but then we miss out on the valuable opportunity to reflect and learn for next time. What could you change next time you have that task to do to make it easier? And of course take time to celebrate and reward yourself for the big wins (and for the small ones). It doesn’t have to be fancy, just an acknowledgement to yourself on a job well done: a walk out, a 5 min jig round the living room, a cuppa and a
slice of cake, a new hand-cream.
Distractions are all around. You need to “be firm with your boundaries” and not let yourself or other people over step them. Learning to say no to people and requests is an important skill to be mastered. However we do always need to allow some margin for unpredictable interruptions and delays. For this reason I recommend only scheduling 60% of your day, leaving 40% for the unexpected! But it is not only others who can distract us from the task at hand. We also need to be disciplined with ourselves. Designate a certain amount of time to use social media, text, watch television, or any other distraction that causes you to mindlessly waste time. These outlets do have a time and place, but often many of us spend way too much time swiping and tapping away the minutes. Instead, allow set time limits to enjoy technology and make sure to power down when the time is up.
Not all things digital are distracting. So do try out some focusing “tools” like the pomodoro technique of focussing in 25 minute blocks, or listening to music like that developed by the team at Focus@ Will, which is designed to help your brain focus; or even wear headphones to block out noise. What works for you?
And finally “move your body”. As I said at the beginning of the article, we have a strong mindbody connection, if you can’t get your mind to play ball, look to your body. Staying active is important - exercise releases endorphins but idleness leads to over-analyzing and overthinking. Creating space in your schedule for you is important. If like me you have a tendency to prioritise work, why not create a vitality check-list of the things you need to do be “healthy” and then book into your schedule time for getting out in nature, going for a walk/run/cycle/swim or doing a 10 min meditation to calm the internal chatter. Keeping ourselves at “OK” or above is going to be imperative in the coming months. Learning to manage yourself is crucial to your ability to thrive rather than just survive, particularly now!
Catherine Evans Joines
MS during lockdown & working from home: You can have your virtual cake, but you can’t eat it!
Angela Taylor
Steroid Metabolome Analysis Core, Institute of Metabolism and Systems Research, University of Birmingham
Scroll through social media and you come across two repeated images;
1. perfect families with parents educating their young children to university standard,
2. a calm and serene home office with a healthy looking potted plant and steaming cup of coffee.
Of course this is a real representation of working from home through lockdown and in my house there were only a few subtle differences. We have focussed more on child-led education, youtube videos- typically of Minecraft and Lego, lots and lots of Lego. My home office is on the kitchen table, an essential placement to allow children easy access to myself “I’m hungry/thirsty/tired/
angry”. With the added bonus of my 4 year old ‘helping’ me work. Here only the hardiest of plants survive and having a hot cup of coffee is a
Pre-lockdown my role was running the Steroid Metabolome Analysis Core, managing our gas chromatography and liquid chromatography mass spectrometers. We are a core of three staff with many researcher and collaborator samples running on our systems. We run a mixture of projects all steroids focused, from clinical trials to lab based PhD research. A typical day would be sample, extractions, analysis and data processing. Like most of the world COVID significantly changed my working day.
Firstly during lockdown I was called to work in the lab, we needed to run patient samples, thus allowing vulnerable patients to avoid hospital visits. This meant my husband had to become a teacher, sorting out our children’s school work, while juggling his full time job from home (thank you Rhys). In the lab I had to re-familiarise myself with GC-MS, a definite love/hate relationship. Thankfully the instrument manufacturer allowed us to have additional access to the analysis software, therefore my colleagues (Lorna Gilligan and Fozia Shaheen) could analyse the data at home while I
was in the lab extracting samples. The three of us were working flat out to get important results to patients and without the ability to analyse data from home we would have been unable to provide results
in the short time periods required. In April our workforce was reduced, as Lorna had a beautiful baby girl, Heather (congratulations!). The utility of virtual meetings soon became apparent to us, an essential tool; the ability to virtually discuss and share data in real-time was crucial, (also with the added bonus of being able to ‘beautify my appearance’ without makeup). We were able to conduct weekly lab meetings with our extended lab group, led by Prof Arlt, where a student or post doc gave a presentation each week, with researchers from Italy, Ireland, Brazil and South Africa joining. This interaction has allowed us to keep coherency in the group, and make sure our colleagues are doing ok. The ability to share presentations and data allowed us to talk through papers and design future experiments, this would have been impossible via phone and email only.
While running the patient samples, we were also running our LC-MS/ MS system at about ~60% capacity, (thanks to my colleague, Lina Schiffer coming into the lab to help with extractions). This was aided through remote desktop applications. Something which in the past I have avoided like the plague (are we still allowed to use this analogy?). However during lockdown making sure samples were running and there are no issues with the system has been one less thing to worry about, (I admit to checking at midnight and first thing in the morning a few times). A further advantage was being able to troubleshoot with our mass spectrometry service engineers remotely, allowing them
to access our system to do basic checks avoiding unnecessary lab visits. The remote desktop allowed us to process the data from home, all peak integration and quantitative calculations were conducted at home. While integrating peaks my son (6yrs) observed “Mummy that looks easy all you’re doing is moving the line over the bump”, I think he’s after my job!
Now lockdown restrictions have been relaxed people are returning to our lab. We have the safest possible working environment, working in shifts with designated pathways around the building, multiple hand wash stations and wearing masks. The amount of samples on our systems is increasing along with the amount of analysis. For the long term we will be completing all analysis at home spending minimal time in the lab, remote access to mass spectrometers and analysis software is essential to this. Without this we simply could not have continued to work during lockdown! I hope, in future, mass spec manufactures will provide additional licenses for home working within their software packages.
The ability to work from home as much as possible allows me to minimise the risk to myself and family, while still generating important data. However the lines between work and home are somewhat blurred, checking the LC-MS is running properly while making dinner, processing some GC-MS data while watching a movieIs this really a positive? Will this balance change when restrictions are lifted?
What will stay and how will our work change? When some normality returns, and the children go back to school, home working will obviously become easier and now I have all the tools to enable me to do this. I think remote and internet based meetings will become routine, this has positives and negatives: you can have your virtual cake, but you can’t eat it!
FEATURE
Alison Ashcroft Thomson Medal 2020
Frank Sobott University of Leeds
Alison Ashcroft joined the University of Leeds in 1997 after 12 years’ as a leader in the development of techniques and their applications in the field of mass spectrometry whilst working for mass spectrometry instrument manufacturers, and applying this expertise during four years in the pharmaceutical industry. Prior to this, Alison was a chemistry undergraduate at the University of Liverpool. She obtained her PhD in natural product chemistry at the University of Manchester before continuing this research with a postdoctoral fellowship at the University of Geneva, Switzerland. In 2014, the University of Liverpool recognized Alison’s work with the Harold Potts Medal for “Outstanding contributions to chemistry”. Alison is both a Chartered Chemist and a Fellow of the
Royal Society of Chemistry.
During her 22 years at the University of Leeds, Alison established the Mass Spectrometry Facility in the Astbury Centre for Structural Molecular Biology and Faculty of Biological Sciences, building the facility from its inauguration with a single instrument (purchased with a grant from the Wellcome Trust) to a facility with an international repute for its ground breaking research. During her Career at Leeds, Alison continued to pioneer the development and application of mass spectrometric methods to interrogate biological systems, specifically in the exciting new field of ion mobility spectrometry coupled to mass spectrometry which enables the separation of protein conformers and measurements of both mass and shape (cross-
sectional areas) in one experiment. This work led to the award of the “Outstanding research publication” from the American Society for Mass Spectrometry in 2009. More recently, for her work in amyloid assembly, she was awarded (with Sheena Radford) the Royal Society of Chemistry’s Cornforth Award in 2015.
Alison has led an active research group throughout her career in Leeds, having supervised 26 PhD students and 14 post-doctoral fellows. As of 2020, she was awarded 39 grants, and has published a total of 168 papers to date (including a text book and several book chapters). Alison has also been involved heavily in FBS teaching, including lecturing, tutorials, practical classes and module management. She was given the “Women of Achievement” award from the University in 2012.
Since 1983, Alison has been heavily involved in the British Mass Spectrometry Society (BMSS), including serving as Chairman, President, and Chair of the Advisory Board. Her input into the mass spectrometry field has been recognized with the award in 2016 of BMSS Life-membership, and in 2019 of the BMSS Medal (a rarely awarded honour to “individuals deserving special recognition by reason of their outstanding and sustained contributions to the British Mass Spectrometry Society in the promotion of mass spectrometry”). Alison was also a founder member of the International Mass Spectrometry Foundation (IMSF) in 1997, and Board member from 1997-2006 (European Representative, then Secretary). The IMSF is a non-profit organization which has 36 member countries and operates the International Mass Spectrometry Society, organizing
meetings and encouraging students from all countries to attend.
In 2020, Alison was awarded the IMSF Thompson Medal jointly with Ron Heeren of Masstricht University.
Biomacromolecular Structure SIG goes Virtual !
Anton Calabrese, Aneika Leney, Joe Gault
The Biomacromolecular Structure
SIG (BMS SIG) was established in 2020, and was scheduled to hold its first meeting in Nottingham on 1-2 July this year. The aim of the SIG is to provide training and a forum for discussion on mass spectrometry based methods for the elucidation of the structure of peptides, proteins, nucleic acids, polysaccharides, and other biomacromolecules. Moreover, the SIG intends to promote the work of early career researchers, and to be a forum where researchers can present their work for the first time in a friendly, welcoming environment. As a result of the COVID-19 situation we had to change our plans for 2020, and given that a physical meeting was not an option we decided to go virtual. We have been running fortnightly meetings over the lockdown period, starting in April and ending in August, as many of us are starting to return to our labs.
Organising this has been a huge undertaking, and we’d like to pay tribute to the work of BMSS in supporting us to deliver this virtual program so successfully, and in rolling it out to other SIGs. The support for these events by the BMS community has greatly exceeded our expectations, with up to 140 audience members on-line per meeting. We have even managed to attract attendees from beyond the UK, including from Europe, Asia, Australia and New Zealand. Throughout the virtual seminar series, PhD students, postdocs, and group leaders all contributed excellent talks that showcased the breadth of mass spectrometry research into biomacromolecular structure. Thanks to the line-up of speakers who rose to the challenge of telling us all about their research via Zoom, including:
• Emma Norgate (University of Manchester)
• Dominik Saman (University of Oxford)
• Lauren Tomlinson (University of Liverpool)
• Ruby Jia (King’s College London)
• Tim Esser (University of Oxford)
• Rachelle Black (University of Manchester)
• Jeddidiah Bellamy-Carter (University of Nottingham)
• Oliver Hale (University of Birmingham)
• Matthew Sinnott (Birkbeck College/ University College London)
• Rani Moons (University of Antwerp, Belgium)
• Rebecca Beveridge (University of Strathclyde)
• Lavrentis Galanopoulos (University of Edinburgh)
• Luise Luckau (LGC)
• Florian Benoit (University of Manchester)
We also had two keynote lectures in the series, the first was from JJ Phillips (University of Exeter) who discussed the use of mass spectrometry methods to study protein choreography, and the second was by Charlotte Uetrecht (European XFEL and Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Germany) who spoke about her work using mass spectrometry to study viruses. Kate Groves (LGC) and Neil Oldham (University of Nottingham) delivered great training talks to guide us through the details of using hydrogen-deuterium exchange and carbene footprinting to study protein structure.
Overall, the 2020 BMS SIG programme has been a resounding triumph, but what we couldn’t provide virtually was the opportunity to network over good food and drink. So, despite the success of this year’s BMS SIG, we’re looking forward to seeing everyone in person at our 2021 meeting!
Ambient ionisation SIG highlights
AP-MALDI with SICRIT
Efstathios Elia National Physics Laboratory
For atmospheric pressure matrix assisted desorption/ionisation (AP-MALDI), several ion sources, operating in a range of geometries have been reported. Most of these platforms have, to date, suffered from relatively low ion yields and/or poor ion transmission compared to equivalent vacuum MALDI sources. These observations have motivated us to seek a method for enhancing ionisation of low abundant molecules in an AP-MALDI MSI setup. Recent advances in MALDI MSI have seen the development of several routes to ionisation enhancement, with laser and plasma post-ionisation amongst others. Many plasma devices used for mass spectrometry are reliant on the direct interaction of plasma filaments with the desorbed analyte plume such in the case of using a Plasma Assisted Desorption/
Ionisation device. Carrying on from this, we have developed a secondgeneration transmission mode (TM) AP-MALDI imaging platform with in-line plasma post-ionisation using the commercially available SICRIT device. We evaluated the ionisation enhancement of the two plasma devices using a selection of molecular standards and mouse brain sections in both positive and negative ion modes. Although both plasma devices showed significant increase in detected ion intensity, the SICRIT device was seen to provide an least an order of magnitude higher ion intensities for the molecular standards when compared to our previous plasma post-ionisation setup. Similar enhancements were observed when analysing a mouse brain section at 20 µm pixel size. The presence of several lipid classes such as galactosylceramides or phosphatidylethanolamines as uncommon protonated species were
observed only when the plasma was turned on, a similarity shared with other means of post-ionisation in MALDI such as laser post-ionisation e.g. MALDI-2. Further work will investigate the mechanisms of plasma post-ionisation and similarities to MALDI-2 and integration of the SICRIT device with other ambient ionisation methods to further enhance sensitivity of low abundant molecules.
sagittal section
791.55) mainly
grey matter
What’s in your paracetamol?
Daniel Burns LGC
The organic mass spectrometry team at LGC's National Measurement Laboratory have been developing a method for the rapid purity determination of drugs of abuse using atmospheric sample analysis probe (ASAP) coupled with a Waters QDa single quadrupole MS. The ultimate aim of the research is to provide a simple, easy to use method which could be used for in-field purity determination. Samples are prepared by dissolving a known mass of sample in a known volume of ethanol containing quinine as a generic internal standard (IS). The sample is then analysed by ASAP-MS with an analysis time of ~2 minutes per sample. The determined analyte/
IS ratio is then used to determine the analyte concentration (and hence purity) using a single-point calibration. For the initial work consumer pharmaceuticals were used as surrogates for drugs of abuse for proof of concept. The testing performed is underpinned by a confirmatory analysis using LC-MS/ MS. Current testing has shown significant promise, with excellent agreement across a number of analytes and dosage formats, all the while maintaining a simple sample preparation and testing scheme designed with non-laboratory environments in mind. The data below shows the results obtained for two different paracetamol products by LC-MS/MS and ASAPQDa showing excellent agreement between the two methods and good agreement with the estimated
Virtual Ambient Ionisation Special Interest Group
purity based on the manufacturer’s specifications. Further testing is planned to assess viability for bulk drug seizures.
The BMSS Ambient Ionoisation Special Interest Group (BMSS AI SIG) look forward to welcoming Dr Gary J. Van Berkel on the 3rd December at 15:00 GMT to present his lecture:
”Open Port Sampling Interfaces: Simple and Versatile Concepts for Liquid Introduction Atmospheric Pressure Ionization Mass Spectrometry.”
To join this AI SIG event please register (free of charge): https://www.bmss.org.uk/bmss-virtual-ambient-ionisation-sig-meetings-2020/ ✪ NEXT EVENT 3rd DECEMBER 2020
Above are comparisons of LC-MS/MS data with a matched labelled internal standard and QDa data with quinine as an internal standard for two paracetamol based product. Data shows good agreement between the two analysis methods and clearly differentiates between differences in product purity in different
Your views on going paperless
The June edition of MassMatters was the first to be distributed via electronic means only – due in no small part to the COVID-19 lockdown, but also as an exercise to determine the viability of going paperless for future editions. As a society, we want to make sure we are providing our publications in a relevant manner and also to ensure we balance our efforts with a greater focus on environmental sustainability. Here are some of the views we received back after distribution of the June edition.
Dear Editor,
I was pleased to receive the low resolution electronic version of BMSS which I prefer to the hard copy. I was particularly interested in the (anonymous) article on how to present one’s work and I would like to make one or two comments. I have had red/green problems for many years and I was delighted to see this mentioned. The worst situation for me is a slide with red text on a green background. Black on yellow is much clearer. Having recently had to acquire hearing aids in addition to long distance spectacles, it is probably a good thing that I no longer go to conferences!
I agree with all the points raised about font style and size, uncluttered slides etc. and I would like to add one or two additional points. When the audience has a significant number of people for whom English is not their first language, I suggested to students that they should try to speak in a simplified subset of English, avoiding long sentences (like this one!) and sentences containing unusual tenses (“Had it been possible to have repeated the experiment prior to the sample being contaminated, . . .”). In addition, one should avoid idioms which often don’t translate well. Few foreigners would understand “One must not throw out the baby with the bathwater” and similar statements. I recall when Dai Games and I were speaking to some French visitors and Dai
in his usual enthusiastic style said the results were on the next slide, “Let’s have a dekko” which led to puzzled looks and mutterings from the visitors.
In conclusion, I enjoy keeping in touch with BMSS, albeit at a distance, and to marvel at the wide range of applications to which mass spectrometry is put these days. I wish the society well for the future.
Yours sincerely, Keith Jennings
Thank you for your insights, Keith! We corrected the ‘anonymous article’ credit in the Hi-Res PDF issue on the website - JJ I prefer a pdf emailed to me rather than a printed copy, since I file documents on my hard drive rather than in a physical library these days.
Cheers, Rachel
Dr Schwartz-Narbonne Sheffield Hallam University
Thanks Rachel! - JJ
I liked the new PDF style for MassMatters.
Congratulations to all those involved in its production. Thanks also to Ashley for all that he has done for the Society throughout his time on the Committee.
See you all soon, I hope.
Best wishes Prof John Monaghan
Thanks John! - JJ
Just a quick feedback regarding the move into the digital publication of Mass Matters.
I think that this is a much better way of getting it into members, perhaps an external link to the BMSS website or PDF in a regular BMSS email update or a Locker message would be suitable?
Moving forwards, I would assume that some members may prefer to have an option to only get the digital edition and not the paper edition. It may be a good idea to have this option and may also save BMSS costs on printing and posting.
Best, Eylan Yutuc Swansea University
Thanks Yutuc, and yes – we are looking at enabling a member option to go paperless, watch this space! - JJ
Although the politically correct answer undoubtedly is to go paperless, I prefer to receive a hard-copy of Mass Matters.
Lucien Tuinstra Liverpool University
Thanks Lucien! - JJ
Reflections in Mass Spectrometry
Jane Thomas-Oates
Chair of Analytical Science in the Department of Chemistry, and Director of the Centre of Excellence in Mass Spectrometry, University of York.
How did you first become interested in mass spectrometry?
I was properly introduced to mass spectrometry and the power of what it can do as a biochemistry undergraduate at Imperial College. Our year 2 protein chemistry lectures from Howard Morris and Anne Dell were very exciting and made a huge impression on me. These were complemented by what I realise now was a very ambitious lab session; we derivatised unknown peptides and saw them analysed to give EI spectra, which we then had to interpret to determine an amino acid sequence. I was instantly hooked, and to this day am still delighted to sit with my calculator and a spectrum to interpret. From that stage early in year 2 there was nothing else I wanted to do but mass spectrometry. There was, perhaps unwisely, no plan B for either my undergraduate research project or PhD applications, so I was very fortunate that Howard accepted me to do my project in his team and then Anne took me on as her first PhD student.
It was an exceptional time to
be starting a career in mass spectrometry. The enormous potential of mass spectrometry for larger molecules, with the advent of user-friendly soft ionization techniques, in particular fast atom bombardment (FAB), and the availability at Imperial of magnetic sector analysers such as the ZAB-HF from VG Analytical that were capable of transmitting and analysing the much larger biological molecules ionized using FAB, represented an unprecedented leap forward in capability. That new instrumentation was state-of-theart at the time and brought within reach for the first time the analysis of a range of biomolecules, including biologically relevant carbohydrates, which became the focus of my PhD.
What do you think are your greatest contributions in encouraging young people to pursue mass spectrometry as a career?
I spent a good deal of my early years in mass spectrometry working on the instrumentation, learning how it works, cleaning it, reassembling it, and stretching it to perform at the limits of what was possible. I developed a love of and enthusiasm for the instrumentation itself, alongside my delight in solving the biological and biochemical problems it allows us to address. Being able to share and transfer those dual enthusiasms, and the pleasure and fulfillment they bring me, to the next generation has been and continues to be a real joy.
Working and sharing those enthusiasms with the next generation of scientists is what really motivates me. I love spending time looking with them in detail at mass spectral data. More recently, time at the instrument with a colleague has become my guilty pleasure. Possibly the hardest thing for me to accept in the last 10-15 years, as my responsibilities have taken me more
and more out of the lab, is that I can no longer reasonably expect to be the most expert instrument operator in the group.
In what new areas could mass spectrometry make a significant impact - are new approaches and thinking necessary for these applications?
Hires pictures in Dropbox It is my belief that real, challenging biomolecular questions derived from the broadest range of disciplines are what drive the development of instrumentation and analytical approaches. State-of-the-art kit and approaches in turn allow ever more ambitious application challenges to be addressed; these then drive further breakthroughs in instrument performance and outcomes, in a virtuous cycle. Cool samples will not yield their best data if the instrument and its capabilities are not fully understood and exploited, while even the most ground-breaking instrumentation won’t teach us much of value if we only ever aspire to analyse mass calibrants.
The quest for ever better limits of detection, as well as mass accuracies and resolution will, I suspect, continue to be a focus, even though the extraordinary capabilities (and designs) of current instrumentation were unimaginable when I started out. Innovative sample handling, while perhaps seen as less glamorous than hardware developments, will continue to play a central role in broadening and deepening applications.
The areas of imaging and, in particular, single cell analysis have massive potential that are still relatively untapped. Informatics and how we deal with the data we generate will need to continue to be huge areas of growth, and I would hope to see the area of miniaturization and fieldable
instrumentation make more big strides.
What advice would you give a scientist starting out in mass spectrometry?
First of all, thoroughly know your instruments and how they work, and identify those application areas that you find inspirational and compelling. Combining an understanding of and hands-on confidence with the hardware, with the potential it has to address important questions, will give you the drive to continue learning, and allow you to push the field forward with your own take on how to apply that kit to answer real questions. Importantly, knowing both instrumentation and its applications also makes you more broadly employable, as many of my former group members know.
Secondly, know how to use and interpret the mass spectral data you can generate. Understanding the chemistry underpinning fragmentation pathways and mechanisms enables interpretation of spectra de novo which makes it possible to elucidate novel structures – a huge satisfaction in itself. Informatics approaches and the information they allow us to access, for example in -omics studies, are seductive and mindblowing. However, I have learned how important it is not to let our inevitable enthusiasm for these outputs and what they could tell us make us forget rigor – we still need to sanity check and manually verify what we think the algorithms and search engines are telling us.
Where do you see the future of mass spectrometry in the next 10 years - can it still be a career path for young people?
Absolutely; a career in mass spectrometry is probably an even more exciting prospect now than it
ever was, given the instrumentation and capabilities we now have at our disposal and the breadth of applications that this brings within our reach. Mass spectrometry is an area in which the UK has significant strengths and a long history, and I see it very much as an exciting and engaging career path for the next generation. Learning your craft as a mass spectrometrist is a delight – the enjoyment and satisfaction to be gained from understanding an instrument and how to make it perform as well as it can to address your scientific questions rigorously is truly satisfying and exciting.
The field of mass spectrometry is still moving very fast; the brandnew technologies that were available to me when I started out, and that revolutionized biological mass spectrometry at the time, have now pretty much completely disappeared. The instruments and the whole way we use mass spectrometry now (for example in -omics approaches) were unimaginable then. This makes being asked to predict the future very tricky. However, I hope that the current trend towards
adoption of mass spectrometry by a broadening user base across ever more disciplines will continue to gain momentum and be an area of significant progress in the next 10 years. Interdisciplinary studies in the areas of the environment, cultural heritage, history and archaeology, climate change and climate studies, and agriculture and food production I believe are all areas in which mass spectrometry is poised to take a much more central role.
Could you describe your lasting memories/most satisfying achievements of your career in mass spectrometry?
Without a doubt the most memorable and delightful aspect of my 40 years in mass spectrometry is the wonderful people with whom I have had so much pleasure working. The young scientists I have had the privilege of training and guiding are what I am most proud of, have made a huge impact on me, and will always have a very special place in my heart.
Through the York Centre of Excellence in Mass Spectrometry,
I have, with my colleagues, been delighted to be able to introduce to mass spectrometry scientists who would otherwise not have had the chance to do their own analyses on state-of-the-art instruments. My amazing collaborators across the range of disciplines into which my biomolecular curiosity has taken me (chemists, physicists, mathematicians, microbiologists, plant scientists, engineers, environmental scientists, informaticists, archaeologists, conservators, and many more) have given me new perspectives, generated endless ideas, and been so central to the work my group has done. Their enthusiasm and patience have kept me learning new things, which is the most enormous fun.
My group members, past and present, have shared and provided all the scientific and less scientific fun, made me laugh endlessly (and cry occasionally), and have been the source of all that is most memorable (you know who you are!).
TRAVEL GRANT REPORTS
The authors of these reports all wish to express their thanks to the BMSS for the award of a travel grant to allow them to attend these conferences.
DGMS
1st - 4th March 2020, Muenster, Germany
Travel Grant Recipient:
Anisha Harris
University of Warwick
Supervisors:
Professor Peter O’Connor
Abstract
Vitamin D compounds are a group of fat-soluble secosteroids, which are vital for maintaining bone health in humans. In particular, recent studies have shown that the dihydroxylated vitamin D 3 compounds: 1,25-dihydroxyvitamin D3 (active) and 24,25-dihydroxyvitamin D3 (inactive) have significant biological effects, playing a role in diseases such as osteoporosis.
Identification and differentiation of the isomers by mass spectrometry can be challenging due to the zero mass differences between them. The isomers may require separation by liquid chromatography (LC) with the presence of a derivitization agent, which can add extra complexity to the spectra. Here, we investigated the use of fragmentation methods such as Infrared multiphoton dissociation (IRMPD), electron induced dissociation (EID) and ultraviolet photodissociation (UVPD), available on a Bruker 12T Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS). A number of isomer specific fragments were observed for 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 using all fragmentation methods, enabling quick and easy differentiation between them without the need for prior chromatographic separation.
Report
Vitamin D compounds refers to a class of secosteroids. Vitamin D 3 is made in the skin from
7-dehydrocholesterol under the influence of UV light and vitamin D 2 is found naturally in plants.1, 2 Vitamin D is metabolised first to 25-hydroxyvitamin D (25OHD), then to the active compound, 1,25-dihydroxyvitamin D (1,25(OH)2D3) whereas 24,25-dihydroxyvitamin D3 (24,25(OH)2D3), also formed from 25-hydroxyvitamin D3 (25OHD3), is inactive as a hormone. 25OHD is the most abundant metabolite of vitamin D 3 but it is also inactive. It is difficult to use 1,25(OH)2D3 as a biomarker for vitamin D 3 deficiency levels as it is only present at very low levels in the blood.
Currently, immunoassays and liquid chromatography-tandem mass spectrometry (LC-MS/MS) are commonly used for detecting and determining the levels of vitamin D metabolites in humans. The medium for the metabolites tend to be in human serum or in blood.
Qualitative analysis of the vitamin D metabolites is usually performed using gas chromatography-mass spectrometry (GC-MS) but the metabolites tend to require derivitization prior to GC-MS analysis to enable differentiation between them. Recently, Qi et al. demonstrated that it was possible to differentiate between 1,25(OH)2D3 and 24,25(OH)2D3 using reactive adducts generated via matrix assisted laser desorption ionisation (MALDI). Even ion mobility-mass spectrometry (IMS-MS) was utilised to study the gas-phase conformations of 25OHD3 epimers.
Vitamin D3 samples of 25-OH, 1,25(OH)2 VD 3 and 24,25(OH)2 VD 3 (kindly provided by Volmer group at Humboldt-Universität zu Berlin) were diluted with water: methanol (50:50, v/v) with 0.1% formic acid
into final concentrations of 10 uM. Experiments were conducted on the Bruker 12T SolariX FT-ICR MS; sprayed by nano ESI (positive ion mode) with EID MS/MS. Electrons were emitted from an indirectly heated hollow dispenser cathode held at 1.5 A. IRMPD data was acquired with a continuous wave 25 W CO 2 laser (Synrad, Washington, USA) with an output wavelength of 10.6 µm. UVPD data was acquired at 213 nm from a pulsed Nd:YAG laser (Litron lasers, Rugby, UK) and also using an ExciStar ArF 193 nm excimer laser (Coherent, UK).
MS analysis of the dihydroxylated vitamin D 3 isomers showed no difference between the spectra. Initial dehydrations (loss of water) were immediately observed in the MS/MS spectra for all species analysed using all the fragmentation methods. Numerous ion series were also observed, showing the typical picket fence series of hydrocarbon chain decompositions. In between these ion series, useful fragments were detected, which can be used for structural characterisation of the molecules.
Overall, the fragments generated due to cleavage of the C-6/C-7 bond in the 1,25-dihydroxyvitamin D 3 compound demonstrate that the fragile OH groups were retained during IRMPD, EID and UVPD MS/MS. These fragments were also noticeably absent in the 24,25-dihydroxyvitamin D3 ion spectra. This can be used to distinguish between the dihydroxylated vitamin D3 isomers. A few more cleavages were also observed by EID and UVPD at 193 nm compared to IRMPD and UVPD at 213 nm. However, the cleavage coverage of the molecules appears to be very similar across
all fragmentation techniques. The standard dihydroxylated isomers were provided but these experiments would be particularly interesting to replicate for the vitamin D 3 metabolites in complex matrices such as blood or urine.
