MASSMATTERS
The official publication of the British Mass Spectrometry Society Edition 95 – May 2022
The Pullen Symposium: Remembering Frank
Welcome to the latest edition of Mass Matters! In this issue we celebrate the life and work of a great friend of the BMSS, Prof Frank Pullen – with a symposium held in his memory in London and the award of the BMSS Medal to another friend, Prof. John Langley. It is a shame that celebratory events are overshadowed by such tragic circumstances that are occurring in the wider world right now – please read our statement on the crisis in Ukraine on the BMSS website :
www.bmss.org.uk/mediacentre/news/bmss-statement-the-crisis-inukraine/
This issue we also welcome Krisztina Radi of Protein Metrics Inc. who joins the BMSS committee as a co-opted member. Welcome Krisztina!
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Disclaimer: Articles published in Mass Matters are not peer reviewed.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 proofread the articles for spelling, grammar and general layout only. Authors must obtain any relevant permission prior to submission, including the permission of the 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.
Chair’s Report
Dear BMSS members,
2022 stretches out before us with the excitement of a full programme of BMSS events and activities.
Preparations are well underway for our Annual Meeting. We return to the Royal Northern College of Music on 13th September with the traditional 3-day conference structure, bolstered with the most popular new features from last year’s hybrid meeting.
Plenary lectures will be delivered by our very own BMSS Medal winner, Prof. John Langley, and Prof. Michal Sharon from the Weizmann Institute of Science, Israel. John’s BMSS Medal was awarded during lockdown, so this party is a long time in waiting! We can also announce that the lively arena that is the traditional poster hall is coming back, and that the flash oral presentations that were so popular last year, will also feature in the BMSS42 programme. In fact, this year will see the inaugural Green Prize awarded for the best flash oral presentation. This new prize in is honour of Brian N. Green, an eminent mass spectrometrist and BMSS Aston Medal holder who was known for his strong preference for very short presentations , and who sadly passed away in December 2021.
BMSS42 is building into a very exciting meeting. Registration and abstract submission are now open, so I encourage you all to sign up and join in, and whilst we very much hope to see you in person, we will be making the conference content available on-line after the event.
The conference season will be kick-started in London, with symposium to honour of Prof. Frank Pullen, BMSS Medal holder, and we have an exciting programme lined up to celebrate the amazing contributions Frank has made to mass spectrometry and to the UK MS community. Conference momentum will be conserved by our SIG groups, who, as always, are simply buzzing with activity. The EFA Sig and ambient ionisation SIG have teamed up to organise a
fabulous one-day event in Guilford, and the more newly established Lipidomics SIG have struck up their 2022 series of on-line seminars with an International flavour. Normality also resumes, thanks to the team at Sheffield Hallam University, who are recommencing their May slot for the Mass Spectrometry Imaging Symposium.
We also have a call out, seeking to recognise an individual, or a group of individuals, who have gone above and beyond the normal expectation at work or in wider society to, promote a more diverse and inclusive mass spectrometry community, and/or championed diversity through leadership and new policies. These individuals will be rewarded with the opportunity to share their work through a keynote lecture. For more information, please check-out the EDI pages on the BMSS website.
For those of you planning to venture abroad this year, the International Mass Spectrometry Conference in Maastricht will be hosting a lecture by our very own Prof. Alison Ashcroft, BMSS Medal holder. Alison was awarded the Thomson Medal in 2020, and will be delivering her Thomson Medal lecture at IMSC24. We are also very pleased to announce that the BMSS (myself and Hannah Britt) will be co-running a Career’s Workshop at IMSC24. This has become somewhat of a tradition for the BMSS, and this year we are honoured to share the opportunity with Isabelle Kohler from Vrije Universiteit, Amsterdam. Come along and hear about career experiences from Alison Ashcroft and other interesting mass spectrometrists, and find out all about the international MS job market!
2022 began with such optimism and hope as we started to emerge from a global pandemic, but as the devastating events in eastern Europe unfolded, our world rapidly turned upside down once again. The BMSS committee were minded to be proactive and so the BMSS will be establishing a fund to contribute financial support for
displaced scientists who identify a host institution in the UK, or to facilitate collaborative projects with partners in our community. As developments arise, information will be communicated through the website.
The UK MS Infrastructure bid project is also gaining momentum. Following a productive session at BMSS41, the final leg of this marathon began with a Townhall Meeting where 250 scientists gathered to participate in what has been re-branded the Critical Mass UK Large Infrastructure Bid. The team is well on the way to delivering a robust proposal to UKRI, and hope to secure circa £100M funding for UKRI to invest in mass spectrometry. As you can see the BMSS committee is as busy as ever, and I must say, it is wonderful to be a part of such a vibrant team. We will be holding elections shortly to fill three committee positions, and so I encourage you all to think about putting your names forward to join the BMSS committee, or nominating your friends and colleagues who you would like to see represent your interests. Should you have any questions about life
on the committee, please just reach out to one of the current committee members to find out more. In the meantime, I look forward to our conference paths crossing throughout 2022.
Dr Jackie Mosely BMSS Chair
Jackie Mosely, BMSS Chair
2022 BMSS membership subscription
Renew your BMSS membership subscription for 2022!
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 benefit from 20% off relevant book titles when purchased via Wiley Publishing (discount code required) publication of the BMSS, published three times a year
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
Recent publications by BMSS members...
N-Terminal Modification of Gly-His-tagged Proteins with Azidogluconolactone.
Brune K.D., Lieknina I., Sutov G., Morris A.R., Jovicevic D., Kalnins G., Kazaks A., Kluga R., Kastaljana A., Jansons .J, Skrastina D., Spunde .K, Cohen A.A., Bjorkman P.J., Morris H.R., Suna E., Tars K. ChemBioChem 22, 31993207 (2021). DOI: 10.1002/ cbic.202100381
Site-specific protein modifications are vital for biopharmaceutical development. We report siteselective α-aminoacylation of peptides, glycoproteins, antibodies, and Virus-like particles (VLPs) with azidogluconolactone at pH 7.5 in 1 h. We multimerised azidogluconoylated SARS-CoV-2 receptor-binding domain (RBD) onto VLPs via click-chemistry, to give a COVID-19 vaccine. Compared to yeast antigen, HEK-derived RBD was immunologically superior, likely due to observed differences in glycosylation.
Modality Agnostic Model for Spatial Resolution in Mass Spectrometry Imaging: Application to MALDI MSI Data.
Metodiev, M.D., Steven, R.T., Loizeau, X., Takats, Z. and Bunch, J., 2021. Analytical Chemistry, 93(46), pp.15295-15305. DOI: 10.1021/acs. analchem.1c0240
A new image resolution mode for MSI is presented, incorporating the influence of sampling probe, the motion of the stage relative to the probe, and the noise inherent from the measurements. The model shows that the size of the probe, stage velocity, and the rate at which the probe consumes material from
the surface govern the amount of blur present in the image. The algorithm was applied to MALDI MSI datasets from silver step edge and tissue samples.
Rapid Cyanobacteria Species Identification with High Sensitivity Using Native Mass Spectrometry.
Green D.H., Leney A.C., Anal. Chem. 2021, 93, 42, 14293–14299. DOI: 10.1021/acs.analchem.1c0342
Harmful algae blooms are flourishing in waters worldwide - a problem that is increasing with climate change. In this paper, we developed a native mass spectrometry assay to rapidly identify different strains of algae. We show that using our method, algae can be detected prior to bloom formation - a finding that is essential for the future prevention of harmful algae blooms.
Integration of Mass Spectrometry Data for Structural Biology
Hannah M. Britt, Tristan Cragnolini, and Konstantinos Thalassinos. Chemical Reviews, 2021, DOI: 10.1021/acs.chemrev.1c00356
This publication reviews methods in protein mass spectrometry (MS), and their contribution to the field of structural biology. The structural MS techniques of native MS, ion mobility, top-down, crosslinking, hydrogen-deuterium exchange, and radical labelling, are described, along with the structural information that can be obtained from them. The review also discusses approaches for integrating the data from structural MS with complementary experimental and computational approaches in structural biology.
Unlocking the potential of biofuels via reaction pathways in van Krevelen diagrams
Diana Catalina Palacio Lozano, Hugh E. Jones, Tomas Ramirez Reina, Roberto Volpe, and Mark P. Barrow
Green Chemistry, 2021, 23, pp. 8949–8963
DOI: 10.1039/D1GC01796A
Pyrolysis of biomass can be used to produce liquid bio-oils, which can be subsequently upgraded for use as biofuels. Using ultrahigh resolution mass spectrometry to characterize these samples, we demonstrate that van Krevelen diagrams can be used not only to visualize the compositions of the bio-oil samples but to plan reaction pathways for upgrading, thus informing future production strategies.
Solvent and Flow Rate Effects on the Observed Compositional Profiles and the Relative Intensities of Radical and Protonated Species in Atmospheric Pressure Photoionization Mass Spectrometry
Mary J. Thomas, Ho Yi Holly Chan, Diana Catalina Palacio Lozano, and Mark P. Barrow
Analytical Chemistry, 2022, (in press)
DOI: 10.1021/acs. analchem.1c03463
Sample preparation and instrument parameters influence results obtained using atmospheric pressure photoionization (APPI), but are often overlooked during the characterization of real-world samples. We investigated the impact of the chosen solvent system and sample flow rate upon signal
intensity, compositional profile, and ion type ratios (radical ion/ protonated species) for different compound types, with consequences for interpretation of complex mixture data.
The Impact of a Graded Maximal Exercise Protocol on Exhaled Volatile Organic Compounds: A Pilot Study
Heaney LM, Kang S, Turner MA, Lindley MR, Thomas CLP. Metabolites 2022;27:370. DOI: 10.3390/ molecules27020370
Two-litre breath samples were collected using a portable breath collection unit prior to, and 10 and 60 min post-maximal exercise testing. Breath VOCs were analysed by thermal desorption-GC-MS. Data showed a tendency for reduced isoprene in samples at 10 min postexercise with a return to baseline by 60 min, supporting previous research to show isoprene levels as dynamic in response to exercise.
Applications of Ambient Ionization Mass Spectrometry in 2021: An Annual Review.
Rankin-Turner S, Reynolds JC, Turner MA, Heaney LM. Analytical Science Advances 2022; DOI: 10.1002/ ansa.202100067
Ambient ionization mass spectrometry (AIMS) has rapidly spread through analytical communities worldwide. This annual review covers applications of AIMS techniques throughout 2021, with a specific focus on applications in key fields of research including disease diagnostics, forensics and security, food safety testing and environmental sciences. AIMS research is increasingly shifting from the development of novel techniques toward efforts to improve reproducibility, quantification, and ease-of-use.
The Frank Pullen Symposium
The Frank Pullen symposium was a true celebration of a wonderful person who much lovely by so many. His support and encouragement of others new no bounds, and not only has he left us with an amazing scientific legacy, but also a great example of how to act as scientists.
Frank’s first [published] contribution to BMSS was at the annual meeting in 1992 in St Andrew’s, where he presented three posters: Studies of Vegetable Oils by Capillary SFC and SFC/MS (A. G. Cheasty, D. E. Games and F. S. Pullen)
Automated Thermospray Mass Spectrometry: A Service to Synthetic Chemistry (D. V. Bowen, F. S. Pullen and J. Sugden) Applications of Maximum Entropy Data Processing in Mass Spectrometry (F. S. Pullen, A. G. Swanson and T. Lee).
In these abstracts, we can see the very beginning of work, initiated by Frank, that would ultimately lead us to open access mass spectrometry, something so many of us take for granted now.
Note, in those days the abstracts were typed, printed and popped in the post to the BMSS meetings team!
The following year Frank joined the BMSS committee. Frank was a hardworking committee member before taking the role of Vice Chair and then Chair (2000-2002). Frank then sat on the BMSS Advisory Board between 2003-07, and then again 2011-15.
So many delegates at BMSS annual meetings will have crossed paths with Frank over the years as Franks was one of our stalwart judges for the Barber and Bordoli prizes. Frank was always so very willing and eager to take up this mantel whenever asked, and I know he relished exploring the scientific endeavours
of our students and ECRs.
A great day sharing great science, just as Frank would like it.
The Frank Pullen Symposium at Burlington House
Mark McDowall
BMSS Meetings Secretary
We learned the sad news that Professor Frank Pullen lost his fight with cancer in September 2021, …just a few days before our 41st BMSS Annual Meeting at Sheffield. The Society, together with numerous colleagues, sincerely regretted the loss of a dear friend, colleague, former BMSS Committee Chair, and BMSS Medal holder. Consequently there was a groundswell of opinion in favor of an event to celebrate Frank’s contribution to our science and community.
As a result the British Mass Spectrometry Society (BMSS) in partnership with The Royal Society of Chemistry - Separations Science Group (RSC-SSG), and the Chromatographic Society (ChromSoc) co-hosted the ‘Pullen Symposium’ on the 08 IV 22 at Burlington House, London. It was a wonderful day with numerous colleagues stepping up to celebrate Frank’s unique legacy - Including Professor Dame Carol
Robinson (Oxford), Dr Jeff Kiplinger (who endured the Covid testing travails of a transatlantic flight to attend), and Dr Cris Lapthorn (Jeonbuk University, Republic of Korea) who contributed with panache on-line.
Frank inspirationally mentored multiple cohorts of colleagues at Pfizer, and subsequently at the University of Greenwich. Frank had an unerring ability to identify latent talent, in candidates that did not necessarily conform to the academic prejudices of the day, …‘self starters’ were assiduously recruited and enabled! Frank’s group inducted a diverse team, …and was ‘ahead of the curve’ in doing so in the 1990s & 2000s. In that spirit the Pullen Symposium 2022 included flash oral/poster presentations from multiple Early Career Scientists.
Following on from the formal proceedings many colleagues repaired to the Kings Head at Mayfair for some ‘Pullenesque networking’, …and a good time was had by all!
Pullen Symposium was well attended with ~100 in-person delegates, and 20 live-stream delegates.
The
Call for helpers!
The BMSS42 organising team are seeking to recruit two Student Assistants to help deliver this year’s BMSS Annual Meeting.
The role will involve staffing the registration desk, liaising with RNCM Staff & BMSS42 delegates, and supporting the sponsors/exhibitors. Where possible the workload will be scheduled to enable some lecture and any necessary poster attendance at the meeting,
To be eligible candidates must be current student members of the BMSS and be available to work at the Royal Northern College of Music, Manchester from 10am on Tuesday 13th of September 2022 through to 5pm on Thursday 15th September
2022. Successful applicants will also have submitted an abstract to present their own research at BMSS42.
In return you will receive free registration, a ticket to the conference dinner, B&B for up to 3 nights, and travel expenses in line with BMSS policies.
Applications are to be made in the form of a letter outlining your suitability for the role and include your supervisor's name and contact details. Please submit applications to the BMSS Administrator, Lisa Sage, at admin@bmss.org.uk. The deadline for nominations is the 24th of June 2022.
Committee Elections 2022
Due to natural turnover of committee member tenures, we are seeking to add
Up to three vacancies are likely to become available, and elections will occur in August 2022, for adoption of the new members at the 2022 AGM, scheduled
• We want you to join the BMSS Executive Committee!
• If you are interested in becoming part of the BMSS Executive Committee and helping contribute to the society, we encourage you to put your name forward!
• We will be looking for candidates to register before 30th June
• All you need to do is submit is a manifesto on why you are a good choice
• To stand for election you must be a BMSS member and be supported by two other BMSS members
• To learn more and to register go to: www.bmss.org.uk/elections/bmss-executive-committee election-2022/registration/
T h e 4 2 n d B M S S A n n u a l M e e t i n g M A N C H E S T E R ✪ 1 3 - 1 5 S E P 2 0 2 2 T H E B R I T I S H M A S S S P E C T R O M E T R Y S O C I E T Y
✪ 3 P l e n a r y L e c t u r e s
✪ 6 P a r t n e r P r e s e n t a t i o n s
✪ 1 2 K e y n o t e O r a l s
✪ 3 6 C o n t r i b u t e d O r a l s
✪ 9 0 F l a s h O r a l s
✪ T r a d i t i o n a l P o s t e r s
✪ S o c i a l E v e n i n g & S u p p e r
✪ F o r m a l C o n f e r e n c e D i n n e r
✪ V e n d o r E x h i b i t i o n
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Photo by Rob Wicks
The 2020 BMSS Medal
Prof. G. John Langley
The BMSS was thrilled to award the 2020 BMSS Medal to Prof. G John Langley of the University of Southampton. Despite a short (!) delay in providing John with his medal (thanks COVID…) we caught up with John to hear his thoughts about his time in mass spectrometry, and the BMSS.
Interviewed by Mervyn Lewis, Associate Editor.
How did you first get involved in mass spectrometry and then the BMSS?
I first encountered chromatography and mass spectrometry in my final year project as an undergraduate student at Swansea University, under the supervision of Jim Ballantine – GC-MS of nutmeg. This was a seminal experience and set the initial foundations for my future career. I went to the School of Pharmacy, University of London in 1984 to study for a PhD with Mike Baldwin. My research was initially around fundamental fragmentation processes, following these with 13C labelled materials, tandem MS (MIKES) a key tool and this extended to kinetic energy release data and links to structure. Another part of my research was method development and application of thermospray to on-line monitoring for patent protection of Trimethoprim (my projected funded by Wellcome), this early LC-MS was extended to work with our pharmacognosy department investigating oestrogenic components in lupins. The fascination with fragmentation mechanisms, data interpretation and hyphenated techniques still burns today; our latest 2D GC-MS instrumentation is amazing and it’s still fun to get to sit and operate it,
and to develop new methods and investigate new application areas.
Mike was a fantastic supervisor and was also BMSS Secretary, so I quickly became aware of BMSS activities and attended my first BMSS three day meeting in HeriottWatt University within 6 months of being in Mike’s research group. I was Mike’s second PhD student, Frank Pullen his first and we struck up a great professional and personal friendship at that point until Frank’s sad passing earlier this year
I joined the BMSS committee in 1998 and spent 4 years as meeting secretary, was secretary for the next 4 years, then 2 years as Vice-Chair and 2 as Chair. Just when I thought I had ‘escaped’ I was invited to join the Advisory Board, a role I enjoyed and believe is the AB is a valuable resource for the Society, maybe one that is underutilised.
I was honoured to be awarded the BMSS lectureship in 2016-17, a role I took very seriously, giving 18 lectures across the UK and covering over 4500 miles (mainly by train!).
During your involvement with the BMSS, what do you think are the most significant changes you have seen in the Society and in the industry?
During my time as meetings’ secretary we moved to employing professional exhibition organisers and this aligned with BMSS employing a professional administrator (the wonderful Anna Upton). The Committee had recognised we needed to change the way we operated to keep pace with the changes across our science. More diversity of applications, users, instrumentation, added automation, LC-MS moving from a SIG to a core technology/tool. We also moved to engaging professional conference organisers for our Annual Meeting,
many of us still remember that first event at Reading.
The use of MS has continued to grow and with it more and more users work with mass spectrometry every day, many of these probably still don’t see a nature home or link to BMSS, I think this is a challenge for us as a Society. Similarly, the hyphenation of Chromatography and MS is now ubiquitous, we need to ensure the MS doesn’t become ‘just a detector’, though already, in some cases that is rightly what it is.
It’s been interesting to follow the changing face of MS over the last 40 years. As a student I handed my sample over to the MS operator, Bryn Fussell, who returned the data some time later. That’s what we had at Southampton when I came here in 1988, 1 person manually analysing all samples. Now we have walk up and use system, used by undergrads, postgrad, PDRAs and even staff! Other changes reflect the growth in application areas and the different sciences and
scientist that now need MS. With this had come a major change in diversity. MS users now reflect society, and not the predominantly ‘man in a basement with a precious, complicated spectrometer’ that I recall from the 80s.
How has the BMSS evolved to reflect and adapt to these changes?
We have adapted, often proactively changing, the employment of professional administrators and conference organisers allowed the committee to focus on the science and core BMSS business, e.g., ensuring the sustainability of the society, provision of travel grants (I think the best thing me do) to allow for attendance at meetings. The Committee model ensures there is always new blood joining, and there are always plenty of volunteers wanting to join, which I see as a great vote of confidence in the Committee and Society. Whilst churn can be high on occasions, the AB provides the legacy knowledge
INTERVIEW
for the Society. Even when you are no longer an official member of this the odd phone call comes (you can never fully leave ).
Where do you hope to see the future of the UK mass spectrometry community and how do you hope the BMSS can continue to support its members?
Education and providing a platform to share research (meetings), vibrant special interest groups to share topic specific knowledge and support have to be the future. For me, networking and passing on knowledge and experience are core activities. Friends and contacts made at meeting can last a lifetime. I still recall the first BMSS member (outside Mike’s research group) who came up and spoke to me at my first Annual Meeting, similarly I recall my first meeting with many of our younger members who I met at their first BMSS meeting.
Having a voice for mass spectrometry across the UK and with EPSRC is a challenge BMSS have picked up. This is going to
science, spreading to other UKRI funding. Making this work across the diversity of application areas and users is a massive challenge, one I believe we can meet as a body, but we need to make this as open and encompassing as we can. The political messaging to the funders must be there, the worth of MS to UK research and economy is huge, we must get that message across.
The future must be tackling the next challenges head-on, as we have in the past. Data is now a huge challenge, curating and using these data, processing, and extracting information, interpreting these data (we need better tools), maybe taking a step back and working across disciplines will help. It’s all complex data, also learning from the big data groups, my phone knows what I should buy next before I do, based on algorithm trawling data. Maybe one day I’ll have the answer to the MS/MS data interpreted for me and appear on my phone before I get back to the office from the lab. Now that would be cool.
What are your lasting memories of your time in mass spectrometry and of your time on
Fun, just great fun, wonderful people, passionate about their science and wanting to give back to the Society. Definitely a work hard – play hard community, never forget the analgesics, these are essential to get you through MS conferences.
You have recently been awarded the BMSS Medal for 2021 - how does this make you feel?
It’s very rarely that I am speechless, this award is top of that list! So honoured, the medal and certificate have pride of place in my office. I had no idea this was in the offing, even when the preamble to the award was being delivered during a Zoom meeting, I was still blissfully unaware (apologies to anyone who was on-line who can lipread when the penny finally dropped).
a Professorial Fellow (Enterprise) and Head of SCAS Southampton Chemistry Analytical Solutions (SCAS).
His research interests are in the application of separation science and mass spectrometry for chemistry, chemical biology, agrochemical and petrochemistry as well as probing new applications and areas for research.
John has held many positions within BMSS, including service as Chair, Vice-Chair, General Secretary, Meetings Secretary and Advisory Board member. In 2016, he was awarded the BMSS lectureship and in 2020, the award of the BMSS Medal for his dedicated championing of mass spectrometry in the UK and further afield.
Diary Dates
Prof. John Langley received a mass spectrometry PhD from the University of London, where he started his working career. He has been based at the University of
St Anne’s College
Sir Peter Ratcliffe | University of Oxford
Perdi Barran | University of Manchester
Evangelia Petsalaki | EMBL-EBI
Manuel Mayr | Kings College London
Sabine Flitsch | Manchester Institute of Biotechnology
Christopher Tape | University College London
Matthew Collins | University of Cambridge
Anne-Claude Gingras | University of Toronto
Mike Gilette | Broad Institute of MIT and Harvard
Melanie Bailey | University of Surrey
Claire Eyers | University of Liverpool
Alfredo Castello | University of Glasgow
Hagan Bayley | University of Oxford
Protein-protein interactions (PPI) and networks
Instructors: Ed Huttlin (Harvard Medical School) | Sandra Orchard (EMBL-EBI)
MORE INFORMATION TO FOLLOW
Native/Structural Proteomics | Systems Biology/Networks | Towards P5 Medicine | Chemical Biology | Bioinformatics | Imaging and Spatial Proteomics | One Health Research | Next Generation Technology
www.bspr.org
In Memoriam: Friends we have lost in 2021
In Memory of Prof. Fred W. McLafferty, a personal perspective.
By Peter O’Connor
In August 1991, I joined Cornell University Department of Chemistry as a new MSc/PhD student. I’d never heard of Fred McLafferty at that time, and my first encounter with him was when he presented a 30-minute brief overview lecture about his research as part of our Saturday morning ‘Research Saturday’ meetings which were quite short but intended to give new PhD students a sense of what the various professor’s research groups were about.
I remember him talking about the wonders of mass spectrometry and that a recent publication from Richard Smalley had used collisions of Buckminster Fullerene with helium in a 4-sector mass spectrometer to show that C60 gained 4 Da during the collision and the only way that could happen was if the helium had popped through and been captured in the middle of the buckyball cage. It was fascinating and his comment was “I wish I’d thought of it!” In retrospect, clearly his career didn’t need that discovery, but I loved the sentiment.
I was searching for a PhD advisor; Fred had just retired that year, at the age of 68, and scuttlebutt was that he might not take any more PhD students. So, I went and asked him. He laughed at my blunt question and explained that yes, he was retiring, but that he’d made a deal with the dean that he could keep
his research, his labs, his office, and his students, all he had to give up was his teaching and his salary. By that statement, I was convinced Fred was a true scientist who loved his work and wasn’t just making a living out of it, and I joined his lab a month later. I had never yet heard of the McLafferty rearrangement or any of his other research, but joined on the basis of his charm, charisma, and enthusiasm – as well as the fact that he had several huge labs full of incredible devices and ‘toys’. I knew almost nothing about mass spectrometry at that time, having originally planned on going into molecular modelling, but I was eager to learn. Joining his group was a bit of an accident in that regard, but it was the best accident of my life and changed my life forever and definitely for the better.
Over the four years of my PhD, I came to appreciate him more and more. He was an ideal supervisor, encouraging and challenging at all times and frequently terrifying in the group meetings. You never wanted to present sub-par data or analysis to Fred as you knew he’d skewer you. He was simply the most brilliant person I’d ever met, and could cut to the core of your data and the flaws in your arguments almost instantly. I was a bit lucky as my original focus was on instrument data acquisition systems (computers essentially, which he didn’t understand; he didn’t get an email address until about 1998); my colleagues who were
working on his core competencies of fragmentation mechanisms were routinely skewered. I later came to see that his brilliance was half native intelligence and half depth of experience. He simply knew everybody and everything that had gone on in Mass Spectrometry over the last several decades.
I came to adore his stories. He always had an anecdote which he brought up about whatever the topic of conversation was, and I knew him 10 years before I ever heard him repeat a story. His depth of knowledge and experience was astonishing. Fred was also one of the most the most charming and charismatic people I’ve ever met.
Fred was terrifying in a seminar. He was a force of nature and would always sit on the front row and ask the first question. Even as recently as 10 years ago, I’d get knockkneed when giving a presentation if Fred was there – which was a superb encouragement to get my explanation correct and precise and make sure my data and slides were excellent. I remember a notorious lecture (not mine, thankfully) about the mechanism of electron capture dissociation at ASMS in Dallas in 1999 where the discussion lasted far longer than the presentation and was so heated that the chair had no choice but to allow the schedule to get totally disrupted. Ask some of the old ECD researchers about that lecture at some point, and Fred’s reaction; it was legendary and everyone remembers it.
Fred absolutely loved to argue about science. Sometimes, albeit rarely, he’d play devil’s advocate to stimulate the argument, but he would always respect the data, so the way you won arguments with him was to present him with new data. When the data disproved him, he would drop his argument like a hot potato and instantly jump on board. He was the consummate scientist and clearly believed that in the argument, the truth of science would come out. His combative nature was challenging for many in the field, and asking around, you’ll quickly find many stories along this line, but you cannot argue about the results. He was incredibly prolific scientifically and had immense influence in the field.
Fred was extremely welcoming to his group and especially to his PhD students. We became an extension of his family. I remember many dinners at his house and his wife Tibby’s wonderful tabouleh salad.
Fred and Tibby lived about 1 km from his office and laboratory in Baker Lab, but it was also about 100 m lower in altitude. Every day, Fred would walk to work, climbing those 100 meters, and I’m convinced that his physical and mental health greatly benefited from that regimen. Amusingly, he clearly got great pleasure on inflicting that climb on visitors and outmarching people half his age up that hill, a fate that I personally suffered. Clearly, it was effective as he was giving superb scientific lectures at the age of 90 and lived to within 5 months of his 99th birthday.
As a mentor, he was always supportive, and sometimes not in the way that I wanted at the time. He would absolutely destroy my manuscripts and even one of my early grant proposals with his red pen. Initially crushing and disheartening, I came to realise that his liberal use of the red pen was a mark of enthusiasm and encouragement in his way. He was generous with his criticism and feedback, and it always made my work better.
In my career, he helped me weather several significant career changes
from PhD to Postdoc to industry to return to academia, and his encouragement to apply for the open professorship at the University of Warwick was the only reason I gave it any serious thought. I’d not have even applied without him suggesting it as it was moving my entire life and career to another country and academic system. He even ‘red-penned’ my CV before letting me submit it and found a few typos and errors in the page numbers of some of the citations! His focus on quality in data, argument, and presentation was always forefront.
He was a mentor without peer, and I will miss him.
Fred was not tightly linked to British mass spectrometry. I am his only PhD student, that I know of, to settle in the UK, but he was good friends with Dudley Williams at Cambridge as well as John Beynon in Swansea. That said, he visited Keith Jennings in 1968 and saw that Keith had achieved the first MS/MS results using collisions in a sector mass spectrometer and rushed home to, quite literally, with Michael Gross, loosen the bolts on flanges to create a leak which would cause ions to
Brian N Green
Remembrance words courtesy of Dr Jackie Mosely, Chair
It is with the greatest sadness that the BMSS learned of the passing of Brian N. Green on 17th December 2021.
Brian, was pioneering mass spectrometrist whose work in instrument development and haemoglobin variants has made him a notable name in UK mass spectrometry (https://www.bmss. org.uk/heritage/notable-names-in-british-ms/#brian-n-green), and saw him awarded the Aston Medal in 1996 for his amazing contributions to our wonderful field of science.
Brian recently completed his latest book, The Analysis of Human Haemoglobin Variants using Mass Spectrometry’ and we featured a review of this work in Issue 94 of MassMatters.
fragment. Fred quickly published the results calling it ‘Collisionally Activated Dissociation’, while Keith published a bit later calling it ‘Collision Induced Dissociation’. It created a whole new dimension to the knowledge that could be obtained from mass spectrometry and Fred always gave Keith the credit for the discovery, but the nomenclature dichotomy persists even today. That story is pretty famous, though I wasn’t even born yet, so it’s obviously second hand.
It’s impossible in a couple pages to capture the life of someone with such depth and character, so I’ve tried to give you some of my perspective and impressions. In 2008, however, Michael Grayson did an oral history of Fred which is available on the ASMS website as part of the ASMS mass spectrometry history project. It revealed aspects of Fred that I was not familiar with, but it is utterly fascinating. I encourage people to take a few hours and read the whole interview, it’s extensive. I’ll add a link, below.
In summary, Fred Mclafferty was a consummate scientist, an utterly enthusiastic mass spectrometrist, and an ideal mentor, both during
the PhD and throughout my career. I was incredibly lucky, even blessed, to have met him and been part of his journey and his influence on my life was profound. Knowing Fred, I suspect that almost everyone who ever worked closely with him will have a similar story. He had an incredible life, and we can all only hope to emulate him to some degree. The world, and our small corner of it, is darker for his departure, but his enthusiasm for our science lives on, and my philosophy is that we must do our best to stimulate similar enthusiasm and scientific curiosity in the next generation.
Goodbye Fred. I already miss you, but thank you for simply everything. You changed my life in so many ways that I cannot even imagine who I would have been without you.
Fred Mclafferty, ASMS Oral History project: www.asms.org/docs/oral-histories/ mclafferty-oral-history.pdf
Brian with Eddie Clayton at BMSS at AZ Alderley Park, 2014
Reflections: Mass Spectrometry as a Career Choice
Chris Wooton, Ph.D
Interviewed by Mervyn Lewis, Associate Editor.
Reflections on mass spectrometry as a career choice.
What was your impression of mass spectrometry when you were first introduced to it?
The first time we did real MS interpretation was the first time I met Pete (Prof. Peter B. O’Connor) at the start of my second year of undergrad chemistry. We’d never seen ESI-MS spectra and barely knew what a peptide was. We were given a surprise test; here is an FT-ICR MS FID raw signal, learn how to code your own data interpretation program in MATLAB, code the Fourier transform, process the data to frequency space, then calibrate to a mass spectrum, analyse the fragmented peptide, then de novo sequence it, and hand in the sequence correctly by the end of the afternoon, or fail.
It was an interesting introduction, a bit of a trial by fire. After we cobbled together something to do the FFT and present the data, we calculated every amino acid mass into a spreadsheet, then every difference of every amino acid in m/z, and went hunting through the spectra for all these mass differences and figure out some sequence which half made sense. By 5pm we had something, it was hard work but paid off – and MS hasn’t changed much from this conclusion for me, it is always hard work, but we can attack any problem and solve it with enough effort, and that’s a nice position to be in. Pete always sees what people should be able to do if pushed a little, and everyone achieved in the
tasks. This is exactly like mass spec; it can seem complicated or difficult, but once you push forward and start getting answers you’ll see so much more and get so much more than any other approach; its always worth it and I wouldn’t want to do anything else.
What persuaded you that mass spectrometry could be a good career option for you? Were you attracted by an application of mass spectrometry or excited by the prospect of developing it as an instrumental technique?
I was a masters student looking at PhD positions, I spoke to Pete and he gave me a tour of his lab and what they were working on with FT-ICR MS. After just 20 minutes of chatting I was amazed at what MS, and especially MS/MS could do, and there was no doubt; that’s what I wanted to pursue for the rest of my career.
I had been in a synthesis lab for months trying to create and characterise new species and realizing that proving you have made something special was at least half of the work. But you really needed purified, separated compounds for most techniques. As soon as I learned that you could scan a whole mass range and then isolate individual species for fragmentation and charactersiation; that was a game changer, and I couldn’t believe this wasn’t applied to all areas of chemistry where I knew people were struggling with complex samples that needed analysis but couldn’t achieve this with other approaches.
I dove into applications and really enjoyed all of it. After a while I found that to get better analysis for our most challenging samples
and ambitions; we needed new techniques and instrumentation to accomplish this, so then moved into instrumentation to further pursue these ambitions and possibilities of analysing ever more difficult species and samples.
So definitely a bit of both – I really like creating and developing methods and instrumentation to enable the applications we do that make the technique so unique and impactful.
How did you go about finding your first opportunity in mass spectrometry?
I read through over 400 PhD proposals and position descriptions when I finished my Masters degree. A lot of the most interesting ones were already filled, but the adverts were left up to snare candidates and waste time/hope. I used to read dozens of papers from each
academic before even asking for an interview, this ended up not being the best use of time/motivation. I walked into an interview with Prof. Peter Sadler at Warwick expecting to talk about a PhD in synthetic chemistry, he said it was a joint project with Pete and told me to just pop in to chat on the way out, so I did, he gave me a “surprise interview”… it went well and I got to see what they could do with FT-ICR MS and was hooked. Eventually I ended up being 100% on the MS side of the project in Pete’s group and couldn’t have asked for a better start in MS.
I stayed at Warwick for my PhD and a number of Post-Doc grants. But conferences were the best places to meet people, and I was always heavily encouraged to go to any and all conferences I could attend. At BMSS 2019 in Manchester I was approached by the FTMS experts
from Bruker, they knew of our work and the research group and were looking for new people. I went to tour the facility in Bremen 2 months later, and 2 months after that I was hired as head of MRMS (aka FT-ICR MS) instrumentation R&D. Going to conferences is the most important and impactful experience in research – the opportunities are numerous and available to anyone who loves their subject. The stipend/travel grant schemes run by the BMSS, ASMS, etc were key to this for me and really facilitated creating good opportunities and a network of people to collaborate and communicate with – I couldn’t recommend or appreciate them enough.
In what application fields do you see new opportunities in mass spectrometry?
Truly complex mixtures and MS/MS. Metabolomics, environmental samples, petroleomics, and any complex biological samples.
From a conference recently I was greeted with the phrase “you cannot identify any compound by MS without MS/MS”. And this rings very true.
Once you have identified a compound comprehensively through MS and MS/MS measurements, you can easily observe the species again at the same m/z and say retention time to be happy you have observed a certain species. But without the MS/ MS you could not truly identify a compound.
There is a lot of scope for analysis of truly complex samples, which by requirement of available techniques and patience often require purely MS analysis, or LCMS with only a certain proportion of species being studied by MS/MS. But this leaves too many questions that quadrupolebased isolation cannot accurately answer due to contaminated MS/
MS spectra. New opportunities in UHR-MS/MS (as in – resolution of the MS/MS, not the mass analyser) are sorely needed to get MS/MS spectra of every species, every time, and without ambiguity over their original parent ion.
Developments in IMS are definitely a driving force of similar dreams, by separating species based on a different metric and enabling the isolation of target species for MS/MS this really extends the complexity ceiling for analysis of complex samples. Combinations of IMS and UHR-MS/MS are needed for the challenging samples of the future. We can see many tens of thousands of species in some samples – it would be great to see tens of thousands of MS/MS spectra to match every one of them and allow identification.
What is your opinion about the impact that automation and informatics will have on mass spectrometry?
Automation and informatics are key to realizing the true power of MS and MS/MS analysis. They enable scaling up to true impact of the techniques we develop. But should be approached and validated with caution, through critical analysis of every step and every assumption made. This can really open new routes to analysis and generate vast quantities of data needed for large scale conclusions, as long as it is done carefully and accurately. I believe there is a healthy balance point between embracing new technology and approaches, but also putting the effort and work into making sure they are fit for every purpose and conclusion we plan for them. Only careful and considered approaches survive the initial hype of an idea and make it to true impact on the field/society, and there’s a good reason for that. These techniques have and will continue to change the balance from the mass spectrometrist knowing if the result is good, to
waiting for software to tell them/ decide if it is good or not. This can be very useful, or very dangerous depending on how it is handled and implemented.
Nothing echo’s this more than automated analysis of data and the resulting conclusions. It is very easy to create situations which will show you the answer you want, it does not mean this is in anyway related to the true answer, the devil really does hide in the detail and it is the responsibility of the mass spectrometrist to ensure the fidelity and accuracy of their analysis and their data acquisition.
Those with close relationships to definitive and unnegotiable relationships to their data (e.g. medical MS work/diagnosis) tend to produce the most critical view of their data and thus the most robust interpretations and practices, these approaches are refreshing to see and avoid the misconception that the commonly found answer is somehow the right one, whereas unfortunately the opposite is normally true for many challenging analytes.
Automated identification of biological systems or diagnosis using MS-based approaches (e.g. cancer/ bacteria) are already known and will continue to develop and surpass previous judgement based approaches in both speed and accuracy once enough basis work is done.
It will be exciting to see the new tests or diagnoses which previously required interpretation/judgement which will now be answered directly with accurate MS based analysis.
Could you describe your views on career prospects in mass spectrometry for young people?
Mass spectrometry is an evergrowing field with a distinct feeling of manifest destiny to it. Whatever we have in the world; we can get an MS analysis of it, one way or the other. And this is a great field to grow a career in. Find something
you are passionate about and push forward. Hard. Then you can make a real impact anywhere with MS behind you.
The mass spectrometry field provides opportunities in so many areas for anyone who is willing to work for it, which is very liberating and it's great to be in a field which reveres data and hard conclusions above all else.
It’s a great multi-disciplinary field which benefits from the diversity of the researchers who exist within it. Be that the physicists improving the fundamental instrument performance, the chemists improving methods and understanding, or the biologists creating and preparing the weird and wonderful samples which challenge our instruments and researchers every day.
There are so many areas mass spectrometry has made advances into, and many more on the horizon – any research group or department which wants to study what exists in the world can benefit from one of the many flavors of MS, they just need to be told what it can do. We are a group of problem solvers and curious minds who like to figure things out – if that sounds like you then you might want to give mass spectrometry a good look as it’s a great place to be and a great time to join.
Acknowledgement:
Dr. Christopher A. Wootton is currently Manager of MRMS instrumentation R&D at Bruker Daltonics GmbH & Co. KG, Bremen, Germany where he has the great fortune of developing the highest performance and most flexible instruments in the world – FT-ICR MS. He continues to work closely with his Professor; Peter B. O’Connor of the University of Warwick who not only gave him the opportunity to start in mass spec, but has worked with for many years and made him the mass spectrometrist he is today.
PLENARY LECTURES
• PAOLA PICOTTI
• BERND BODENMILLER
• PIETERNEL LEVELT
• STEPHEN BLANKSBY
SESSION TOPICS
• INSTRUMENTATION AND METHODS
• LIFE SCIENCES AND HEALTH
• FOOD AND (BIO)PHARMA
• BIOMATERIALS
