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March 2019 | ISSN 1356-5559 (print)
www.immunology.org
ImmunologyNews
Media focus: Inner workings of science news
BSI elections: Make a difference for immunology
Connect Immune Research: Parliamentary event
Hats off to immunology:
A tale of two lymphocytes
Immunology News | March 2019Immunology News | March 2019
A WORD FROM THE EDITOR 3
Editorial Advisory Board: Edd James (Southampton) Louisa James (London) Donald Palmer (London) Mihil Patel (Cardiff)
Managing Editor: Jennie EvansSub Editor: Rebecca RamsdenDesign: Qube Design Associates
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© 2019 British Society for ImmunologyThe views expressed by contributors are not necessarily those of the Society, nor can claims of advertisers be guarenteed. The Society, Editorial Board and authors cannot accept liability for any errors or omissions.
The Team
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With 2019 well and truly under way, the BSI has been busy out and about representing immunology and our community to the wider world. To showcase our work in this area and keep you up-to-date with developments relevant to immunology from outside the discipline, we have started up a new section in this magazine, Representing Immunology, which we hope you find informative (pages 20–22).
It’s election time again for the BSI and, with a number of positions available, we are looking for enthusiastic members from all backgrounds to get involved in our work. We can only truly represent the needs of our members with your input and guidance, so we do encourage all of you to consider standing for election.
You can read more on pages 8–9. Please also make sure you vote when the election process opens in April – more details will be available on our website.
Finally, we are looking forward to our 2019 Congress, taking place in Liverpool on 2–5 December. On page 6, our Congress Secretary, Gary Entrican, introduces what you can look forward to there.
Best wishes,
Jennie [email protected]
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ContentsFEATURES:Join a BSI committee
8
Hats off to immunology: an interview with Martin Raff
14
Inner workings of science news18
Society news422
Congratulations25Journal news26
Representing immunology
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Connect Immune Research 20
Immunology News | March 2019Immunology News | March 2019
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VIEW FROM … THE CHIEF EXECUTIVE
Welcome to another excellent issue of Immunology News. I’m sure that you will agree that it continues to be a busy time for the BSI and the immunology field as a whole. I’m now
six months in to my time at the BSI (don’t worry I’m not going to give you a timeline update every issue…) and I never cease to be amazed by what the team here is delivering and the commitment and dedication I see from our members – it is incredibly inspiring.
As noted in the last issue of Immunology News, we have had some changes at President, Board and Secretary levels – a big thank you again to all of those who have completed their terms of office, including Peter Openshaw, our now Past President, and a big welcome to those who have joined. You can read more about your new appointments on pages 4 and 11. In addition, we will soon open nominations for the next round of changes at Board and on our Committees. These are absolutely critical
roles within the BSI and we encourage you to throw your hat in the ring – we’re looking for members who have the ability and passion to have a real influence on BSI work. More info is on pages 8–9.
In other news, we continue to be influential ourselves across a number of different sectors. As part of planning for a ‘no deal’ Brexit, we contributed to a Science and Technology Select Committee consultation explaining our view on the impact that will have on immunology research in the UK. And, just like buses, after 60 years of never having a Parliamentary event we had our second one in two months in November! This time it was to launch Connect Immune Research – an exciting initiative between BSI, JDRF, MS Society and Versus Arthritis to promote the importance of autoimmunity research and to encourage a cross-disease focus on understanding and treating autoimmunity (pages 20–21). With reach across the whole of the immunology field, this type of collaboration plays to the strengths of the BSI and we are looking to develop similar partnerships in other areas, with some early discussions proving fruitful – watch this space for updates!
I also had the pleasure of being a part of this year’s BSI Winter School in Nottingham, which was truly inspirational! The calibre of the Master’s students and those starting out in their immunology
careers was incredible, and their resilience was impressive when they were fending off the ‘dragons’ in the dragons den exercise at the end of the school! This is our next generation of leaders in immunology research and we’re so grateful for the support from Helen Collins, our Education Secretary, and other senior BSI members for making it such a huge success.
And talking of success, we are well in the swing of organising our hugely popular Congress for 2019 (page 6). Personally, I can’t wait for it and I’m gutted that I have to wait over a year for my first BSI Congress! Gary Entrican and the Congress Committee are doing a stunning job as the programme is looking like it will be our best yet. Roll on December!
Keep up the great work everyone!
With best wishes,
Doug BrownChief Executive, British Society for ImmunologyEmail: [email protected]
SOCIETY NEWS
A message from our new PresidentAt our AGM on Tuesday 11 December, Professor Arne Akbar became President of our organisation, taking over from Professor Peter Openshaw after his five-year term of office. To mark the start of his Presidency, Professor Akbar has written an open letter to the membership about his aims for the organisation.
“It is a tremendous honour for me to be elected as the next President and Chair of the Board of Trustees of the British Society for Immunology (BSI). I am currently Professor of Immunology at University College London and have been a member of the BSI since 1978 when I started my PhD, and have been part of the BSI family from that time, through all the subsequent stages of my career. The BSI is widely considered to be the exemplar of an extremely successful organisation and this is due to the seamless interface between the Trustees, who decide on the direction of travel of the Society, and the BSI office who translate ambition into outcome. I would like to give my sincere thanks to Peter Openshaw, the outgoing BSI President, and Jo Revill, who was the CEO in charge of the BSI office for much of his five-year tenure. She left to take on the job of CEO of the Royal College of Paediatrics and Child Health. We are very lucky to have a new CEO, Doug Brown, who has been in post for six months and has already made an impact with his vibrant leadership of the office. I look forward to working with him and his team during my term.
“The current good health of the BSI results from Peter’s strong and visionary leadership. During his Presidency, Peter and Jo restructured the process of Trustee recruitment and built a strong staff team with the expertise to deliver on the BSI strategy. They have also increased the transparency and accountability of all activities across the organisation. Peter
has been involved in many activities behind the scenes including lobbying politicians, driving forward the careers work, building our international presence and improving our membership services. On behalf of the BSI, I would like to offer our sincere gratitude to Peter for all he has done for the Society; it has been nurtured in a very safe pair of hands. He will be a difficult act to follow and I will continue to seek his advice when needed in the future.
“Our CEO Doug Brown leads an office consisting of 15 talented individuals who have portfolios relating to finance, the BSI journals, conferences (including the annual Congress), external affairs and much more. Doug obtained a PhD in immunology so in him we have a CEO with inside knowledge of the field. This staff team is there to benefit the members and I would encourage everyone to look at the BSI website to learn more about their activities. They would be delighted to hear from you and to answer any of your questions.
Doug and I aim for even more interaction between the Trustees and the office staff in the future to give everyone involved a better global perspective of our activities.
“It is a well-known saying that ‘in science, we all stand on the shoulders of giants’. This can be re-articulated as anything we may do is perhaps incremental on things that have been done already. The BSI now has over 3,700 members who are mainly based in the UK but also reside in many other countries, and financially we are in an extremely stable position. Rather than resting on our laurels, we are investigating novel ways of expanding our activities, without excessive risk, to promote immunology for the benefit our members. British immunology has had a major role internationally even before immunology was recognised as a discipline in its own right. Some examples of success include the discovery of vaccination (Edward Jenner), the concept of immune tolerance (Peter Medawar), the discovery of antibody structure (Rodney Porter), the concept of autoimmunity (Ivan Roitt), the use of biologic therapy for the treatment of inflammatory diseases (Marc Feldmann and Tiny Maini) and many others. These are the giants on whose shoulders we all stand. Therefore, as British immunologists, based on previous achievements, we can hold our heads high on the international stage. Our ambition is to promote a secure base of support that can nurture the next set of giants in immunology among the BSI membership.
“In my four-year tenure as President, I would like to seek closer interaction with other immunological societies worldwide to identify ways for interaction that will benefit our members. I also aim to find ways to promote closer interaction with immunologists in the biotech and pharma sectors. The BSI is heavily dependent financially on our journals, Immunology and Clinical & Experimental Immunology, and the proliferation of new competitor journals and open access publishing is something we need to respond to and we will continue to evolve our publishing offer to make the most of all opportunities. Nevertheless, the Society is in excellent financial health and we are exploring, collectively, new initiatives to use our resources to secure our outstanding current position and to benefit our members. We have made great strides in securing an equal gender balance in our committee members and
invited speakers at Congress; however, there are still improvements needed such as the progression of ethnic minorities to senior positions in immunology that need to be explored then addressed. Finally, the success of these ambitions will only be possible with a close partnership with the Trustees and the CEO Doug Brown and his staff. My job is to ensure that we all work together for maximum benefit of the BSI and its members.”
Arne AkbarPresident, British Society for ImmunologyEmail: [email protected]
‘Our ambition is to promote a secure base of support that can nurture the next set of giants in immunology among the BSI membership.’
Arne Akbar Arne Akbar with Peter Openshaw
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UPCOMING BSI MEETINGS
BSI meetingsBRITISH SOCIETY FOR IMMUNOLOGY CONGRESS 20192–5 December 2019Liverpool, UK
We have lots of upcoming meetings covering a vast array of immunological topics. Find out more at www.immunology.org/events.
©Shutterstock/Shaun
BSI Immunometabolism GroupFUELLING THE IMMUNE RESPONSE: UK IMMUNOMETABOLISM MEETING 201914–15 March 2019Newcastle, UK
BSI Infection & Immunity GroupBSI TRAUMA IMMUNOLOGY WORKSHOP27 March 2019 Birmingham, UK
Wessex Immunology GroupIMMUNOREGULATION3 April 2019Southampton, UK
BSI London Immunology GroupIMMUNOLOGICAL MEMORY5 April 2019London, UK
BSI Oxford Immunology GroupOXFORD IMMUNOLOGY SYMPOSIUM23–24 April 2019Oxford, UK
Immunology Undergraduate Prizes
The next round of applications for our Immunology Undergraduate Prizes is now open. These awards aim to promote excellence in the study of immunology at undergraduate level, and to encourage gifted students to pursue further postgraduate study and a career in immunology.
The application deadline is 29 April 2019 and further details can be found at www.immunology.org/grants-and-prizes/immunology-undergraduate-prizes.
BSI sponsored meetingsFrancis Crick Institute and Nature Publishing Group WORLD IMMUNOLOGY DAY - CANCER IMMUNOLOGY SYMPOSIUM26 April 2019London, UK
BRITISH SOCIETY FOR RHEUMATOLOGY ANNUAL CONFERENCE 201930 April–2 May 2019Birmingham, UK
BSI Inflammation & Edinburgh Immunology GroupINFLAMMATION: FROM INITIATION TO RESTORATION24–26 April 2019Edinburgh, UK
BSI West Midlands Immunology GroupWEST MIDLANDS IMMUNOLOGY GROUP SYMPOSIUM14 May 2019Birmingham, UK
BSI Regional and Affinity Groups
At the BSI, we’re already looking forward to the end of the year and our much anticipated Congress 2019, which is taking place at the Arena Conference Centre in Liverpool on 2–5 December. Here, our Congress Secretary, Gary Entrican, takes you through some of the highlights that you can expect and why you should get involved.
The BSI Congress has always been a fixture in my calendar and marks a very special time of the year in December. This will be my first Congress as the organisation’s Congress Secretary, a role that I’ve found exciting, challenging and educational. It has been a pleasure to work with BSI Congress Committee and the staff in the BSI office who have been hard at work to ensure that we bring you a Congress that caters for the breadth of immunology, with cutting-edge and innovative topics. The programme incorporates suggestions and ideas submitted by BSI Regional and
Affinity Groups and the BSI membership. We have also taken into account delegate feedback from Congress 2017 in Brighton.
To whet your appetite, we’re delighted to announce that the keynote speaker will be Doreen Cantrell, Professor of Cellular Immunology from the University of Dundee. Professor Cantrell’s research is at the forefront of T cell biology, adopting a multidisciplinary approach to examine how antigen receptors and cytokines control the development and immune activation of T lymphocytes. This is sure to be a fascinating session and a must-see for all immunologists.
Following this, we have three days of exciting and varied immunological content. Plenary sessions will include ‘Immunological challenges of controlling influenza’, ‘Tissue resident memory T cells’, ‘Cancer immunotherapy’, ‘The recognition and clearance of senescent
cells by leukocytes’, as well as two joint sessions with our friends from the UK Primary Immunodeficiency Network (UKPIN), ‘Learning from cell signalling in immunodeficiency’ and ‘Mechanism of inflammation in immunodeficiency’.
Other highlights of the conference promise to be our ever-popular Bright Sparks event to showcase the fantastic work being carried out by our early career colleagues, and the multitude of parallel sessions that we have on offer, with topics to suit all immunological tastes. Additionally, we have many opportunities for attendees to give oral and poster presentations during the conference and I do encourage you to submit an abstract to the event. The BSI Congress offers a wonderful opportunity to network with your immunology community and showcase your work to leading researchers from around the world.
So, mark the date in your diary and visit our website for more information. I look forward to seeing you in Liverpool!
Gary EntricanCongress SecretaryBritish Society for Immunology
Find out morewww.immunology.org/bsi-congress-2019
@bsicongress
Dates for your diary
Abstract submission deadline:
9 September 2019
Early bird registration:
25 October 2019
Conference dates:
2–5 December 2019
Join us at the BSI Congress 2019 in Liverpool
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New review series from CEI : Pathogens in Autoimmune DiseaseWe are pleased to announce that the latest Review Series from Clinical & Experimental Immunology, ‘Pathogens in Autoimmune Disease’, is now available to download from http://bit.ly/2Gmk6SA.
Guest Editor Urs Christen (Goethe University Hospital Frankfurt, Germany) has assembled articles that reflect on the current evidence for the involvement of pathogens in the etiology and/or pathogenesis of autoimmune diseases. Although many associations between pathogen infections and the occurrence of autoimmune diseases have been reported, firm proof of a detrimental or a protective effect is rare.
There are several reasons for this. On the one hand, the involvement of many additional factors such as genetic susceptibility, diet, exposure to chemicals, microbiome diversity, stress, sunlight exposure, and many more has been demonstrated. On the other hand, it is very likely that not a single pathogen infection, but rather the sum of all pathogen infections acquired
throughout a lifetime, determine which and how many autoimmune diseases affect a given individual. Thereby, some pathogens might have an accelerating and some a decelerating effect.
We all have been and will be infected by a multitude of pathogens throughout our lifetime, some of which might be involved in the initiation and/or acceleration of a disease, others which might display protective properties, and others again which might have no impact at all. This review presents articles that report on the pursuit of possible suspects.
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Join a BSI committee and make a difference for immunology!
Nominations to stand for election for various positions on the BSI’s committees, including on our Board of Trustees and our policymaking Forum, are now open. This is a fantastic opportunity for members to get involved in the work of the Society and make a real difference to immunology in the UK.
Our Trustees have the chance to make an active and dynamic contribution to the Society through their responsibility for setting and overseeing our strategy, governance and finances, and by working closely with our CEO and staff to support all our members. Forum is the Society’s ‘think-tank’ and is charged with
developing policy and overseeing other areas of activity for the Society, such as education and careers work, public engagement, media, policy and public affairs, which includes helping to formulate responses to external consultations. The membership of Forum is designed to be representative of the Society’s membership, including individuals from all career grades and immunology sectors.
Please check your emails and the BSI website for details on how to nominate yourself. Nominations will close on Tuesday 19 March. Voting for all positions will be open from 2–26 April and full details on how to vote will be circulated to members shortly. The election results will be announced on the BSI website the following week.
Why should I stand for election?
We are looking for committee members from all backgrounds and career grades and are very keen to encourage nominations from across the spectrum of our membership. For most positions, you don’t need to have previous experience of sitting on a committee, but you do need lots of enthusiasm and a willingness to get involved to help formulate our activities and policies. This is an exciting time to be involved with the BSI, as we move forward with our strategic plan to support members at every stage of their career and broaden our external profile.
Getting involved with a BSI committee provides a platform, and gives you the opportunity to have your say and help shape the future of the Society and immunology in the UK. It gives you the chance to work with our staff to formulate activities and policies, to reach a wide network of scientists and to help forge our direction to support the next generation of immunologists. We can only truly represent the needs of our members with your input and guidance.
‘We are looking for committee members from all backgrounds and career grades and are very keen to encourage nominations from across the spectrum of our membership.’
The current BSI Board of Trustees
BOARD
• General Trustee (two vacancies starting in mid-2019) – Trustees make active and dynamic contributions to the Board, using their wide-ranging skills, knowledge and experience to ensure good governance and the development of strategy for the Society. They feed into wider activities which help enhance the work of immunology. Trustees are appointed for four years, may be elected for a second term, and may not serve more than two consecutive terms. They are expected to attend Board meetings in London four times a year.
• Clinical Secretary – Sofia Grigoriadou finishes her term of office at the end of 2019. The Clinical Secretary takes the lead for the development and delivery of the Society’s clinical activities. In addition to responsibilities of a general trustee (outlined above), the role-holder will also chair the BSI’s Clinical Committee. Working closely with the BSI team, they will ensure that the BSI maintains good links with the clinical community and develops activities to support our members in this sector. The Clinical Secretary will chair four Clinical Committee meetings per year (two via teleconference) as well as attending the quarterly Board of Trustees meeting.
Vacancies FORUM
All Forum members are expected to attend committee meetings in London four times a year.
• Clinical Representative (from summer 2019) – Magdalena Dziadzio finishes her co-opted term of office on Forum. This position is open to any BSI members working in the clinical field.
• Early Careers Representative (from summer 2019) – Simon Jochems resigned from his role on Forum at the end of 2018. This position is open to any BSI members who are up to three years into their postdoctoral (or equivalent) career.
• Industry Representative (from summer 2019) – this is a newly created position on Forum to ensure that the voice of immunologists working in industry is represented in our discussions. This position is open to BSI members working in industry at all levels.
Dates for your diary
Nominations close:
Tuesday 19 March 2019
Voting opens:
Tuesday 2 April 2019
Voting closes:
Friday 26 April 2019
Results announced:
Tuesday 7 May 2019
‘Getting involved with a BSI committee provides a platform, and gives you the opportunity to have your say and help shape the future of the Society and immunology in the UK.’
Why should I vote?
Your vote really does count. Your elected representatives will make numerous decisions on your behalf, such as fees for membership and Congress registration; which issues are lobbied on at a government level; how funds for travel awards are apportioned; what career support we provide to members; and many more issues besides, so engaging with the elections genuinely does make a difference.
You can only vote if you are a current member, so please ensure that your membership is up to date.*
*Voting is open to all paid categories of membership. Please note,
this excludes undergraduate members and low income economy
overseas members who do not have to pay a membership fee.
“Joining the BSI Board of Trustees has been extremely rewarding. This is an exciting time for immunology and for the BSI and being a Trustee guarentees both a front seat from which to watch our science evolve, and offers a real opportunity to influence the direction of this evolution. I highly recommend it.”Prof Simon Milling, BSI Trustee
Immunology News | March 2019Immunology News | March 2019
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New BSI Board members
10 SOCIETY NEWS ADVERTISEMENTS 11
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Emission from five antibody-fluorochrome conjugates are distributed across excitation by three lasers
(405nm/488nm/635nm, Figure 4), matching commonly used instrument configurations and retiring the need for
compensation of spillover emissions.
(1) Alexa Fluor* 647 (2) Alexa Fluor* 700(3) APC-Alexa Fluor* 700 (4) APC-Alexa Fluor* 750
The example data shown below demonstrates the assessment of a dose response curve including positive and negative
controls (Figure 5). The degranulation of CD63 and CD203c follows different dose dependencies and kinetics [2].
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Joint virtual issue: A collaboration with the Biochemical SocietyCelebrating increasing collaboration between societies, the British Society for Immunology and the Biochemical Society have created this co-curated interdisciplinary collection from our journals.
This collection combines articles from both the BSI’s journals, Immunology and Clinical & Experimental Immunology, and the Biochemical Society journals. It features key topics across the field of immunology that greatly benefit from interdisciplinary thinking and collaboration, including autoimmunity, immune cell development, immunometabolism and inflammation.
With this joint issue we emphasise the need for interdisciplinary collaboration for scientific advancement and innovation. We believe that connecting different disciplines and solving problems with a holistic approach is crucial to meeting future challenges and improving health and well-being. We hope to encourage sustained collaboration between scientists and across different organisations to ensure continued progress in the life sciences field.
We hope you enjoy reading this collection of articles. All articles are free to access online until 6 April 2019. Find out more: www.immunology.org/collaboration-with-biochemical-society.
Our Board of Trustees is crucial to our work as they are responsible for overseeing our business activities and ensuring the Society is well-run, financially sound and that it meets its charitable aims and objectives. We were delighted to welcome three new Trustees to the Board in January. You can find out more about them in the profiles below.
DIVYA SHAHBSI TrusteeSenior Portfolio Developer, currently Acting Head of Infection & Immunobiology team, Wellcome
“During my career I have worked in university, research institute, charity and funding environments, acquiring a diverse range of laboratory, scientific and strategic skills. After completing my PhD in Immunology, I undertook postdoctoral fellowships in Toronto and London, publishing in the field of T cell immunology and immunotherapy. In 2015, I joined the Science division in the Infection and Immunobiology team at Wellcome, the UK’s largest biomedical research charity. I contribute to the development and implementation of the science strategy, policies and funding initiatives. As well as ensuring the effective delivery of our funding activities, I work collaboratively with various stakeholders to develop special initiatives to highlight the key challenges and opportunities for future research, most recently in immune-mediated inflammatory diseases. I enjoy engaging with a variety of audiences, from interacting with school children through my STEM ambassador work to talking to scientists about their latest research.
“As a new Trustee, I am looking forward to the opportunity to act as an ambassador for the BSI to advance their mission in supporting early career researchers, promoting equal opportunities in immunology, and being a representative for alternative careers that a PhD in immunology can lead to.”
ANN AGERBSI Chair of ForumProfessor in ImmunologyCardiff University
“I joined the BSI as an early career researcher more than 30 years ago and have benefited enormously from the excellent and tailored support offered by the Society at all stages of my career. As a Trustee, I will bring my knowledge of working in academic and clinically-related immunological research in universities and institutes in the UK and the US along with my experience of leading on training and mentoring early career researchers. As a past President of the UK Cell Adhesion Society, I have worked with academia and industry nationally and internationally to advance excellence in scholarship.
“The realisation that altered immunity underlies many common disorders not traditionally viewed as immune-mediated has increased awareness of immunology, both within and outside the biomedical community. The public interest in immunology that I’ve witnessed through participation in nationally-led initiatives, such as ‘Soapbox Science’ and radio interviews, has taught me that patient groups and lay committees are some of the strongest advocates of research. The emergence of fake news emphasises the BSI’s important role in promoting immunology, public engagement, and influencing policy through providing professional advice. As Chair of Forum and a BSI Trustee, I will support the BSI in achieving these aims.”
EMMA CHAMBERSBSI Early Career TrusteeResearch Associate, Division of Infection & Immunity, University College London
“As an early career immunologist, I am excited to take up my position on the BSI Board. I have been a member of the BSI since my I started my immunology career, undertaking my BSc in Immunology 14 years ago at University of Bristol. Since then I have completed a Master’s and PhD in Immunology at King’s College London and I am now employed as a postdoc at University College London, working on ageing and immunosenescence. I have seen first-hand what a brilliant organisation the BSI is – through organising local and national conferences, as well as providing travel grants to help scientists attend the vital meetings. I was an early career representative on the BSI Forum and really enjoyed championing early career scientists and issues affecting them. I have also been a vaccine ambassador for the BSI; I have seen first-hand the excellent public engagement work the BSI is performing.
“As a new Trustee I hope to support and promote early career researchers – encouraging the BSI to provide more support and funding for ECRs. I also believe that there is more the BSI can do to support parents attending conferences. Finally, I strongly believe that the BSI should play a more active role counteracting the misinformation spread about vaccines.”
Find out more about our Board at www.immunology.org/about-us/our-people/governance.
©K
ateryna Kon/ShutterstockJeffries
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Discover the benefits: What it means to belong to the BSI
Spelling out your membership in numbers... (representing an approximate 12-month period)
ImmunologyImpact Factor
3.358~15 days to first decision
Clinical & Experimental Immunology Impact Factor
3.542~12 days to first decision
78% of members surveyed would submit research in the future
8,463
attendees last year
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Immunology News | March 2019Immunology News | March 2019
14 FEATURE ARTICLE FEATURE ARTICLE 15
Hats off to immunology: an interview with Martin RaffOne of the stand-out papers in the archives of Immunology, one of the BSI’s official journals, is a 1970 work by Martin C. Raff entitled ‘Two distinct populations of peripheral lymphocytes in mice distinguishable by immunofluorescence’.1
Martin Raff worked at University College London (UCL) for over 30 years until his retirement in 2002. He is now an Emeritus Professor at UCL, and continues to contribute to the scientific community through his work on scientific advisory boards. He trained as a clinical neurologist in Boston before pursuing an opportunity to improve his knowledge of basic science in Mill Hill, London. The move brought him to the heart of the UK’s immunology community, where he worked with remarkable scientists such as Avrion Mitchison, and produced a series of papers investigating lymphocyte biology.
The remarkable paper he published in Immunology outlines Raff’s investigation into the heterogeneity of lymphocytes, then an important and relatively new field of study, and how to distinguish classes of lymphocyte. To investigate the question, Raff compared lymphocytes from normal mice and from T-cell-depleted mice, discovering that one class of lymphocyte (now known as B cells) were Ig-positive and theta (θ)-negative, while T cells were θ-positive and Ig-negative. He had shown earlier in a Nature paper that Thy-1 is a marker for mouse T cells, which enabled this field of enquiry to flourish.
Nearly 40 years after this remarkable paper was first published, Immunology’s Editor-in-Chief, Danny Altmann, braved a rainy November evening to meet Martin in his office at UCL’s MRC Laboratory for Molecular Cell Biology and talk more about T cells and B cells, a remarkable four years in the history of immunology, and the enduring importance of a good title.
Danny Altmann: It is wonderful to meet you Martin. I wondered if you could tell me more about the story behind this paper?
Martin Raff: I’d only been doing basic science and immunology for about a year and a half when I sent this paper off to the Journal of Experimental Medicine, which was quite unusual! In my view it was an important finding, but I was new and I just didn’t know that much about how you deal with the politics of science. Anyway, it was bounced right back without refereeing, saying that there is nothing novel here. I have to say, in re-reading it now, the importance of the finding was certainly not obvious from the title. It’s a pathetic title! Even in the discussion the real importance was not emphasised. The quick rejection should have pointed out to me that this was not the right title.
Titles have always been important. You know that 0.0001% of people are going to read your whole paper. 0.001% will read the abstract. And 0.01% will read the title. So, 99.9% of your readers will miss the message if it is not in the title.
Anyway, I was unsure what to do next so I went to my mentor, Avrion (Av) Mitchison, to ask for advice. He was on the editorial board of Immunology, so he suggested I submit it there.
DA: Av had the idea that the thymus was something to do with the different kinds of lymphocytes or programming subsets of lymphocytes. So where did it start from?
MR: I was a board-certified neurologist when I first started in science at Mill Hill in London. I had decided to do a few years of basic science to gain some lab experience. I chose Av’s lab because I couldn’t understand what he wrote about – I thought maybe others would struggle too and be put off applying to work with him, so I’d have a better chance of getting in his lab.
When I arrived he gave me a project. He said he’d heard Arnold Reif describe this antigen called θ (now called Thy-1) which was on thymus and brain cells, but not in peripheral lymphoid tissues. Av thought, ‘Well, T cells come from the thymus, maybe this would be a good marker for them’. This was the early days of T cells and B cells, and one was really desperate for markers to distinguish them.
So that was my project, and it worked even though I knew no immunology. That was largely because I was surrounded by many immunologists who knew a hell of a lot, and I just kept asking questions and asking how to do things. My first paper was published in Nature and showed that Thy-1 marked T cells. It made use of mice that were depleted of T cells, and I found that the mice had dramatically reduced numbers of Thy-1+ cells in their peripheral lymphoid organs, so it was pretty clear that Thy-1 was on T cells. And then I wanted to use immunofluorescence to look at Thy-1 on the surface of T cells. In a control experiment, I found that fluorescent antibodies against mouse immunoglobulin (Ig) on its own stained mouse peripheral
lymphocytes; and Roger Taylor, working across the hall, found the same thing using radiolabelled anti-Ig antibodies and autoradiography. We published our findings together, showing that there is Ig on mouse lymphocytes, but we didn’t know which type of lymphocytes they were.
The Immunology paper showed that the lymphocytes with Ig on their surface did not have Thy-1 on their surface, suggesting that they were B cells. The finding that the Ig-positive cells were increased in T-cell-depleted mice, whereas Thy-1-positive cells decreased, supported this conclusion.
DA: It’s good science.
MR: It’s good science, but that should have been the message in the title of the paper!
DA: That’s the joy of hindsight, isn’t it?
MR: Well, it should have been in my head, because when I sent my first paper to Nature, John Tooze, the handling editor, said ‘really interesting stuff, but you’ve got
to change the title’, which should be the main message of the paper – that θ (now Thy-1) can serve as a T cell marker in mice. I can’t remember what the original title was – but it was clearly as boring as this one on the Immunology paper!
What’s interesting about that was that Schlesinger and Yron published pretty much the exact same findings about θ in Science a month before I did and reached the same conclusion. But their title was as bad as my original one, and they never received as much credit as I did, thanks to John Tooze.
DA: And Jacques Miller was onto something similar as well?
MR: Not quite. In fact, when Miller came by to visit Mitchison back then, I’d only been in science for about six months. Because he was a competitor of Av’s, I asked Av what I should do. Should I tell him what I was doing? Av said, ‘Yes, tell him absolutely everything’. So, I did, and, when Miller asked if he could have some anti-θ serum, Av said, ‘Give him as much as you can spare’. This was Av’s way, and it turned out to be an invaluable lesson for me that served me well for the rest of my career.
DA: What were your impressions of UK immunology? What kind of crowd were they?
MR: Well, I was new to the field so couldn’t compare it with anything, but it was all terribly exciting. I mean, Mill Hill was abuzz with great immunology. The BSI was really important. That’s where I learned a lot of immunology.
DA: How were BSI meetings in the ’70s? What was exciting to see?
MR: There were hundreds of people at the BSI meetings. They were big
‘Titles have always been important. You know that 0.0001% of people are going to read your whole paper, 0.001% the abstract and 0.01% will read the title. So, 99.9% of your readers will miss the message if it is not in the title.’
meetings, because immunology in Britain was big. The BSI meetings had people from all over Europe and America. They were very good meetings.
It was exciting to see the beginning of the T and B cell story. Tony Davis was one of the people working on T and B cells, Dick Gershon was doing research with Tony, and Av had attracted a lot of outstanding visiting immunologists studying T and B cell interactions – it was the beginnings of understanding these interactions. That’s why Av was in competition with Mitchell and Miller, because they were looking at these interactions in one way, and Av was doing it another way, but they were coming to similar conclusions.
For me, starting from scratch and knowing almost nothing about anything, let alone immunology and science, those three years were the most important and productive in my career. I mean, it was downhill from there!
A point that I make over and over again whenever I can is that Av would not put his name on any of my papers. That’s a remarkable thing. Av once told me, ‘I think when you’re a mentor you have an obligation to your students to promote their careers. And clearly, letting you publish on your own greatly promoted your career.’ And yes, it did. But on the other hand, the θ project originated with him, and he made the first anti-θ antiserum for me. It’s not right that his name was not on at least the first paper – it’s an inaccurate history of what actually happened.
DA: And he was a young man, it wasn’t like his career was safely established at that point.
MR: Av did all of his own experiments, and he mainly published his own results. He didn’t rely on his students’ and postdocs’ experiments. He wasn’t treating me differently from the other postdocs
Figure from Raff 1970 Immunology 19 637–650. Photomicrographs of indirect immunofluorescence of living BALB/cells in suspension. (c) Spleen cells treated with VBS and then Fl–anti-MIg showing ring fluorescence. (d) Spleen cells treated with anti-θ and then Fl–anti-MIg showing both ring cells and the cap cells.
Immunology News | March 2019Immunology News | March 2019
16 FEATURE ARTICLE FEATURE ARTICLE 17
and students. Anyway, it’s why I’m a scientist today. I owe him big time. He is a great scientist, mentor and person.
DA: He was very influential in my career as well. I think to young immunologists who inhabit a world of 100,000 lymphocyte subsets and mass spectrometry, it’s very hard to understand a time of only one or two lymphocyte subsets.
MR: It is so interesting to compare then with now. Those times were unusual. In part, because so little was known that almost every set of experiments I did was a discovery. The immune system is so accessible. I mean, you take the thymus out of a mouse and you get a hundred million individual cells. It’s remarkable. When I started to do neurobiology and was able to get tens of thousands of individual cells out of the optic nerve of a rat, I realised what an exception the immune system is: In some cases, I was able to do one experiment in the morning and another in the afternoon – then read the results and plan what I’d do the next day. Those were special times.
On the other hand, the tools were relatively primitive. For example, you had to make your own antibodies and label them; there were no commercial sources or kits. But the life of a scientist was relatively simple, I think. There was relatively little career anxiety: I was not aware of anyone worrying about a job, or about getting papers published, or getting grants. There were so few scientists compared with today.
DA: Lots of people who might not know you were an immunologist will know your textbook, Molecular Biology of the Cell. Decades of scientists have grown up with it. What do you think about students now who perhaps get more of their information from Wikipedia than from a book like yours? Do you think they’re missing out?
MR: That’s a very important question. As you know, the textbook publishing industry is in some disarray – partly because of the rental market and e-books, but also because fewer students read textbooks, especially in the US. There is the added problem of e-book piracy, especially in China.
When we started writing Molecular Biology of the Cell, Bruce Alberts, Keith Roberts, and I spent a summer at Jim Watson’s house in Martha’s Vineyard. None of us apart from Jim had ever written a textbook, none of us had ever taught cell biology. We set out to emphasise concepts, trying not to load the student with facts unless there was a story to tell. As so few stories were known, we often had to make informed guesses to give the facts a plausible context. I think this helped make the book special.
Watson was a co-author on the first few editions. He already had another a very successful book, The Molecular Biology of the Gene. He really brought the idea of conceptual writing from his first book, and we carried it over into this book. The first two chapters that were written (one of them was in immunology) went out for review to university teachers and got trashed because the reviewers thought this conceptual approach would not work for an undergraduate textbook. Nonetheless, the publisher was bold, and with Watson as a famous and successful author, he borrowed a million dollars and went ahead anyway.
Are textbooks still needed in the age of Wikipedia? I think probably yes. If a student wants to find out about a cell biological subject using Wikipedia, it could be pretty tough going. The motivation and storyline are usually missing: ‘Why should I be interested in this subject?’ Another reason I think textbooks will remain useful is that the amount known about most subjects is now probably hundreds of
times greater than what it was when I was an undergraduate. And the brain has not increased significantly in its ability to learn. When we wrote Molecular Biology of the Cell there were very few interesting stories you could tell about a particular protein, whereas now there are many hundreds of stories for many proteins. How can you guide the student through this morass when there are well over 20,000 distinct proteins? Both the teachers and students need guidance, and a good textbook can help provide it, and, importantly, can also provide motivation for why it is worth learning the stuff, although this should be a large part of the teacher’s job.
DA: After your time working on the immune system, you moved into the field of neurobiology. If you were heading the Gates Foundation equivalent for neurobiology, what would you fund?
MR: I would probably invest in new technologies. Paul Allen, who co-founded Microsoft with Gates, set up the Allen Institute, which did a tremendous service for neuroscience by mapping the expression of most mammalian genes in the mouse brain, and, later, the human brain, which greatly accelerated our understanding of these genes in the brain. Although new technologies have already revolutionised neurobiology, given the brain’s complexity, technology is still limiting progress in understanding brain function. That is the safe answer to your question, as trying to predict the future is a mug’s game.
DA: How easy do you think it is now to have a career like yours, which has been so interdisciplinary, and has spanned so many different fields?
MR: It’s a good question. It is certainly much harder now then it was in my day. Just to keep up with progress in one narrow field is now much harder, as so much more is known and so many more scientists are now in the field. It’s great that so much of the information is readily available on your computer screen and that the tools one has to work with are so much more powerful, but thinking time is becoming limiting, which is unfortunate, as an hour of thought can save you months of work.
DA: I think we can be very technologically driven now, and not always in a positive way as we accumulate huge datasets without the brain wattage to analyse them.
MR: True. But, on the other hand, big data can be extremely important: cracking the human genome, for example, revolutionised human biology and human disease research. But big science and
‘It’s great that so much of the information is readily available on your computer screen and that the tools one has to work with are so much more powerful, but thinking time is becoming limiting, which is unfortunate, as an hour of thought can save you months of work.’
REFERENCES
1. Raff MC Two distinct populations of peripheral
lymphocytes in mice distinguishable by
immunofluorescence. Immunology 1970 19 637–650
2. A Citation Classic is a highly cited publication as
identified by the Science Citation Index, the Social
Sciences Citation Index, or the Arts & Humanities
Citation Index. They were gathered by Current
Contents between 1977 and 1993, accompanied by a
commentary by the authors. The full collection can be
found at http://garfield.library.upenn.edu/classics.html.
Further information
This interview is part of ‘Celebrating Immunology at 60’. Find out more at www.immunology.org/news/celebrating-immunology-60.
Immunology has been supporting the work of the BSI since 1958. Profits derived from the sale of the journal are invested back into the BSI, providing major financial support for the Society’s activities – including our travel grants, Regional and Affinity group meetings, BSI Congress and more. Find out more about submitting your research to Immunology at www.immunology.org/news/immunology-call-for-submissions.
huge data sets don’t bypass the need for thoughtful, simple, experiments.
DA: Martin, thank you for your time. It was been wonderful to speak with you.
MR: I should say one other thing about my Immunology paper. When it was published in Immunology, the journal’s impact factor was low, especially compared with the Journal of Experimental Medicine, which was at least ten times higher,
maybe more. Yet the paper became my first and only Citation Classic2 whereas my Nature papers from the same time did not, even though Nature had a much higher impact factor even than the Journal of Experimental Medicine. The lesson I have taken from that is that it doesn’t matter where you publish something: if it is important, it will be found, and that was well before papers were available on the worldwide web, so It is even more true today. So, hats off to Immunology.
©N
IAID
/CC
-BYfries
Immunology News | March 2019Immunology News | March 2019
18 19FEATURE ARTICLEFEATURE ARTICLE
BSA Media Fellowship: inner workings of the science newsAs an immunologist, I have always had a strong personal interest in how the media can shape a national or global conversation around topics such as vaccination, disease outbreaks or immunotherapy breakthroughs. Media reporting can, in quite a tangible manner, change the behaviour or perceptions of an individual in the context of health and disease, and therefore can shape our society for better and for worse.
Speaking out for immunology
It is critical therefore, that immunologists have voices that are heard by the public, and by policymakers, in making an informed contribution to these local, national and global discussions. Presenting a balanced perspective on multiple fronts is essential for ensuring that misinformation or ‘fake news’ is not the only voice that is heard. For the past few years, I’ve been honoured to be given the opportunity to act as a media spokesperson for the British Society for Immunology, a role that has given me the chance to contribute to discussions and news reporting on topics as diverse as influenza vaccination, the devastating effects of Zika virus infection, and potential cures for the common cold.
The fellowship
Last year, I was thrilled to be awarded a British Science Association (BSA) Media Fellowship in the summer of 2018, and even more delighted to find out where I would be undertaking my placement.
Essentially, a BSA Media Fellowship offers scientists, at any stage of their career, the opportunity to spend between two to six weeks embedded within a mainstream
media outlet. Some of the organisations that take part in the scheme include Sky News, The Guardian, and the Financial Times. I was lucky enough to be placed within BBC Scotland, based at Pacific Quay in Glasgow. The funding for the fellowship comes from the individual’s host institution – in my case, I was given the full support of Edinburgh Napier University, where I am Director of Research of the School of Applied Sciences and Associate Professor of Immunology & Infection.
The fellowship is designed to give scientists and academics training and mentorship
from professional journalists, with a focus on how to engage the public with science, and how the media and scientists can work together to ensure facts are at the forefront of a story. As a highlight, fellows also attend the British Science Festival and work within the press room, reporting on some of the highlights from the festival.
Inner workings of BBC Scotland
As part of my fellowship, I rotated around three areas of the news teams that are housed within BBC Scotland; BBC News online, BBC Scotland television news and BBC Radio Scotland. I spent a brief period with the individuals in each of these teams and worked alongside the journalists, the presenters and the producers, who work together with the rest of the production team to deliver the final output.
I reflected on some of the ‘lessons learned’ from my fellowship, and the experiences that changed my perception of the BBC in particular, but also how it changed me as a
‘It was incredible to watch the journalists at work, piecing together a coherent narrative for the story, writing the copy and editing the video, all within the space of just a few hours.’
researcher and a science communicator. I felt that these could be distilled into areas such as journalistic integrity, attention to detail, as well as the requirements for a good science story, and the enthusiastic appetite that the public has for new discoveries as a result of cutting-edge research.
In terms of integrity and detail, the journalists, particularly those in the online team, pay incredible attention to detail in terms of how articles are worded, and are fastidious about how facts are verified. I was proud and gratified to be able to see this first hand, and noted that all discussions around a news story were debated in an open manner. The senior journalists I worked with gave me the opportunity to attend the ‘morning meeting’ where all the stories of the day were discussed, and it was fantastic to see how they found the most interesting aspects of each potential news item, and discussed how it would fit in, particularly in the context of other ongoing news items.
Tailoring content for different types of media
In the context of how science was presented to the public, this was one of the most eye-opening parts of the fellowship. I learned that the medium could emphatically dictate how a story was presented, and how much effort and time would be spent piecing together a cohesive narrative that gave the science a chance to shine. Journalists have to absorb a significant amount of information very quickly, and decide whether there is a story there, and if so, how to present it to the public. This is an extraordinary skill.
For example, many of the senior journalists were very experienced at putting together story packages that could be used for radio, for television and for print media. The BBC Scotland science correspondent, veteran journalist Kenneth Macdonald, was very generous with his time and took me through his process for putting together a story on using satellite imagery to track wild fires from space. He emphasised that, in the case of television, the visuals for a story were particularly important. For radio, this emphasis could shift somewhat, and become an informed discussion between the researcher and a reporter or presenter. For online content, a blend of text and visuals, as well as links to further sources of information could be presented.
It was incredible to watch the journalists at work, piecing together a coherent narrative for the story, writing the copy and editing the video, all within the space of just a few hours.
Polishing image presentation
In terms of how this experience directly influenced my work, my group has made subtle changes to how we capture and present data. For example, if we were using confocal microscopy to look at intracellular proteins, we would now perhaps go the extra step in addition to capturing a selection of still images required for quantification. For example, we might perform a Z-stack and create a 3D representation of the cell, not necessarily because we need it, but because it might look great on TV. It also doesn’t look too shabby in conference presentations either!
In the time since I completed my
fellowship, I have continued to work with some fantastic colleagues in the media, and to encourage some of the researchers in my own institution to do the same. It’s such a rewarding experience to see your own work, and the work of your colleagues, presented in the media, and I’ll continue to encourage and support those individuals who are thinking about how they could reach a wider audience.
Peter BarlowDirector of Research, School of Applied Sciences and Associate Professor of Immunology & InfectionEdinburgh Napier University
‘Presenting a balanced perspective on multiple fronts is essential for ensuring that misinformation or ‘fake news’ is not the only voice that is heard.’
Find out moreThe British Science Association Media Fellowships provide a unique opportunity for practising scientists, clinicians and engineers to spend two to six weeks working at the heart of a media outlet. Applications for their 2019 scheme are now open. You can find out more at www.britishscienceassociation.org/media-fellows.
©Shutterstock/B
igMouse
©Shutterstock/M
acrovector
Immunology News | March 2019Immunology News | March 2019
20 21REPRESENTING IMMUNOLOGY
The charities have come together to establish ‘Connect Immune Research’ – a first-of-its-kind coalition to promote a multi-disciplinary approach to autoimmune research and grow funding and research infrastructure in order to develop new treatment and diagnosis options. Traditionally, autoimmune conditions have been researched and treated in disease-specific silos, but underlying common immunological mechanisms have indicated the benefit of a joined-up research approach.
On Monday 26 November, the British Society for Immunology, in partnership with the type 1 diabetes charity JDRF, MS Society and Versus Arthritis, hosted a parliamentary event to raise awareness into autoimmune conditions and to ask MPs and other stakeholders to pledge their support for this important area of research.
‘Connect Immune Research is a first-of-its-kind coalition to promote a multi-disciplinary approach to autoimmune research and grow funding and research infrastructure in order to develop new treatment and diagnosis options.’
In the UK, approximately 4 million people have been diagnosed and are living with an autoimmune condition; the incidence is rising by up to 9% each year for some conditions. The direct and indirect cost to the UK of just three of these conditions – type 1 diabetes, multiple sclerosis and rheumatoid arthritis, together is estimated to total around £13 billion per year and rising. Up to a third of patients have multiple autoimmune diseases making management of their conditions and symptoms a daily effort. Understanding the commonalities between these conditions could bring a number of benefits, including an improvement to patient quality of life and an increased efficiency to the way these conditions are diagnosed and treated in our NHS.The parliamentary event was used as a platform to launch our new joint report ‘Are you #AutoimmuneAware?’ and to highlight the need for greater recognition and investment for autoimmune conditions as a distinct research area, alongside the likes of cancer, infectious disease and dementia. Hosted by former Health Minister Philip Dunne MP, the event aimed to put autoimmunity centre-stage and for us and our partners to engage with many MPs and sector leaders to explain the UK’s world-leading contribution to autoimmune research and why a joined-up approach to studying the underlying causes of autoimmune disease could allow research
Connect Immune Research: parliamentary event
‘The event aimed to put autoimmunity centre-stage and for us and our partners to engage with many MPs and sector leaders to explain the UK’s world-leading contribution to autoimmune research’
to progress faster, reducing costs and speeding up development of treatments for people with autoimmune conditions. After Philip Dunne’s introduction, we heard from Karen Addington, CEO of JDRF UK and Chloe Gillum, a paediatric nurse who lives with three autoimmune conditions. We also heard from Dr David Hunt, one of the recipients of the inaugural Connect Immune Research grant. The team from the University of Edinburgh, led by Professor Yanick Crow, will use the funding to measure interferon levels in different autoimmune conditions to better understand the relationship between interferon and autoimmunity. Despite a direct timetable conflict with one of the Prime Minister’s Brexit statements in the House, the event was well attended with a number of notable MPs including
Shadow Business and Industrial Strategy Secretary Chi Onwurah and former Liberal Democrat leader Tim Farron. We also hosted representatives from the Medical Research Council, Wellcome Trust, ABPI and other big patient charities.
The most central part of the event was of course the patient supporters representing the partner charities. These were people of all ages living with multiple autoimmune conditions who have taken on a role to inspire others and advocate for their conditions. Engaging with the supporters and hearing about their experience of living with autoimmune diseases was something I found most valuable from the event. I spoke to one 17-year-old girl about living with type 1 diabetes and coeliac disease – she explained so clearly the ins and outs of blood sugar monitoring. It was a particularly
REPRESENTING IMMUNOLOGY
valuable opportunity to bring these patients together with several immunologists whose research is aiming to improve their lives. This is hopefully only the beginning of a revolutionary new way of thinking about and understanding autoimmune conditions. If you have not already pledged your support, please do so using the hashtag #AutoimmuneAware through your social media channels. We also encourage you to write to your local MP advocating for autoimmune conditions.
Shannon LacombePolicy & Public Affairs Manager, British Society for Immunology
Find out more• Read our report ‘Are you
#AutoimmuneAware?’: http://bit.ly/CIRReport
• Read the full press release:
http://bit.ly/CIRPressRelease • Read more information on the first
grant funded through this initiative: https://jdrf.org.uk/understanding-the-role-of-interferon-in-autoimmunity/
• If you have any queries on this
initiative, please email Jennie Evans ([email protected]).
BSI CEO Doug Brown with our President Arne Akbar
Philip Dunne MP opens the event The BSI Public Affairs team at the event
Chloe Gillum talks about what it’s like to live with three autoimmune conditions
Immunology News | March 2019Immunology News | March 2019
©Shutterstock/LightSpring
22 REPRESENTING IMMUNOLOGY
Away from the adversarial exchanges on Brexit that attract most of the media’s attention, our nation’s policymakers continue their less conspicuous behind the scenes work. For many MPs this will include working in one or two cross-party alliances, known as ‘All Party Parliamentary Groups’ (APPGs) that focus on a specific subject or country of interest. One of the most relevant of these groups to the BSI is the APPG on Vaccinations for All, chaired by the SNP health spokesperson and consultant breast cancer surgeon, Dr Philippa Whitford MP. In January, they launched a report called ‘The Next Decade of Vaccines’ setting out what needs to be done over the next ten years to dramatically improve vaccination coverage across the globe.
At the moment, only 7% of children in the 73 least developed countries receive all 11 of the WHO’s recommended 11 essential vaccines. The commonly used DTP3 indicator has stalled at around 85% since 2010, while growing vaccine hesitancy in Europe and the US makes it more difficult for the west to be respected as global
leaders on these issues. The report makes a number of innovative recommendations aimed at improving vaccination coverage; these include increasing the UK’s funding of Gavi, the Vaccine Alliance, and the Global Polio Eradication Initiative, and calling for all global immunisation stakeholders to raise their immunisation targets to encompass full access to all 11 WHO recommended vaccines for children everywhere.
It is an interesting read, and an important one if we are to ramp up the
New report on global challenges for vaccination
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I n n o v a t i o n w i t h i n r e a c h
pressure on governments and other organisations to ensure that the benefits of immunology are available to everyone.To read the full report, visit http://bit.ly/NextDecadeofVaccines or to discuss further, contact the author, Yasmin Mahboubi, at RESULTS UK by emailing [email protected].
Matthew GibbardPolicy & Public Affairs Manager, BSIEmail: [email protected]
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The Association of the British Pharmaceutical Industry (ABPI) recently released a new report called ‘Bridging the skills gap in the biopharmaceutical industry: Maintaining the UK’s leading position in life sciences.’ This skills survey and report highlighted a significant concern around a lack of highly skilled candidates for jobs in the biosciences sector, with immunology in particular cited as an area of high concern where this skills gap is most pressing. Ensuring that the UK has sufficient skills within its workforce is key to maintaining our successful pharmaceutical and biotech sectors and our world-leading reputation in immunology. The ABPI warned that, if we are to meet the government’s target of boosting spending on R&D to 2.4% of GDP by 2027, significant action needs to
be taken now to ensure the UK has a skilled workforce able to deliver this commitment. In response to this report, the BSI’s President, Professor Arne Akbar, commented, “Immunology is an exciting growth area that covers some of most innovative research with real potential to transform diagnostics, treatments and preventative measures that we are able to offer patients. The UK ranks first amongst the G7 nations for our research in immunity and infectious disease, but we can only maintain this strength if we have the skills in our workforce to allow this pioneering work to proceed. Our own observations concur with the ABPI’s findings and we too call for a step change for more funding to attract high-quality candidates into the discipline and to nurture them through their training and development. This increase in core
New report highlights skills gap in biosciences sector
strength, coupled with the UK maintaining an outward looking and open focus, will promote the collaboration with and recruitment of highly-skilled specialists in immunology from around the world.”
You can download the full report from the ABPI’s website at http://bit.ly/2VaMFpK.
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Immunology News | March 2019Immunology News | March 2019
25 MEMBERS’ ACHIEVEMENTS
Congratulations This is the section of the magazine where we celebrate the achievements of our members. Our congratulations to all who are mentioned here.
Immunology Teaching Excellence AwardWe’re delighted to announce that the winner of the 2018 British Society for Immunology Teaching Excellence Award is Dr Jenna Macciochi, Teaching Fellow in Immunology at the University of Sussex.
Dr Macciochi completed a BSc in Immunology at the University of Glasgow before conducting her PhD at Imperial College London. Since joining the University of Sussex two years ago, she has worked hard to put immunology firmly on the map for all life sciences, pharmacy and medical undergraduates. “Jenna has taken several steps to innovate the curriculum with diversified teaching methods to breakdown the challenging nature of immunology concepts, including use of technology to create an interactive classroom environment, which is particularly useful to engage students in large teaching groups,” commented Professor Alison Sinclair, Director of Teaching & Learning at the University of Sussex. “She is collegiate and outward looking and transmits her obvious passion for the subject. This has led to an almost doubling of students taking optional immunology modules and several students going on to pursue immunology-related paths after graduating,” said Sinclair. This view was reinforced by her students, many of whom contacted us with their thoughts: “A very efficient, helpful and hard-working lecturer who always is there to help students with any queries they may have,” and “her teaching ultimately has led to me studying for a Master’s in Immunology.”
The judges felt that Jenna was a dedicated and passionate immunologist who uses
We would love to hear from you about your achievements. Have you or a colleague recently received grant funding, passed your PhD viva or accepted a new appointment? If so, let us know by emailing [email protected].
Travel grant successThe following members were recently awarded BSI travel grants:
Sarah Buchan, Emma Campbell, Slater Clay, Kyle Cunningham, Laura Duffy, Joshua Gray, Amandeep Kaur, Federica La Russa, Roisin Loftus, Owen Moon, Spyridoula Nikou, Shelly Pathak, James Phelan, Ana Pires, Fabian Salazar, Alyssa Silva Cayetano, Ine Vanderleyden and Lotus Westerhof.
The next application deadline is midday, 1 May 2019. More information at www.immunology.org/grants-and-prizes/travel-awards.
Dr Jenna Macciochi
innovative techniques to inspire that love of the discipline in others. Her dedication to sharing best practice with her colleagues and tailoring her teaching style to suit her students’ learning styles has paid dividends in boosting immunology teaching at Sussex. It was clear to the judges that Jenna’s teaching skill was valued by students and colleagues alike and had led many students to pursue a career in immunology.
You can read more about this award scheme at www.immunology.org/grants-and-prizes/immunology-teaching-excellence-award.
New Year’s HonoursCongratulation to Iain McInnes (University of Glasgow) who was appointed a CBE in the New Year’s Honours list for his services to medicine. On receiving the honour, he said, “It is lovely to receive this surprising but most welcome honour reflecting the extraordinary efforts of our team as we combat arthritis and seek to improve the lives of those affected.”
Placement award schemeThis BSI scheme supports PhD and medical students to conduct an extended placement. A recent award was made to Mae-Yen Tan (University of Glasgow) to study ‘Developing a novel strategy to identify acute myeloid leukaemia (AML) specific surface targets’ at the University of California, San Francisco on a two-month placement.
The next application deadline is 1 June. You can find out more at https://www.immunology.org/grants-and-prizes/summer-placement-award-scheme.
Communicating Immunology grantsOver the last few months, the BSI has funded four projects through this scheme. Debby Bogaert and colleagues (University of Edinburgh) received a grant for their project ‘World Pneumonia day; teaching the public about infections and antibiotics through music’, whereby a range of pneumonia-related public engagement activities were carried out including a performance of the musical ‘The mould that changed the world’ by a professional theatre company. Sheena Cruickshank (The University of Manchester) and Mellissa Fisher received funding for a science/art collaboration, which saw artist Mellissa taking to the lab and using a PillCam to take images of her own intestinal tract. Amanda Midgley and colleagues (University of Liverpool) will run ‘Superhero Team in your Body’, involving an engagement stand focused on immunology at the Smithdown Road Festival in May. Jill Johnson (Aston University) was funded for her project ‘Synapse – bringing immunology and young women together’, a two-day workshop at Birmingham Science Museum with Girl Guides from the area. Activities included building an antibody using lolly sticks and felt balls, and using French knitting techniques to create a vascular bed containing immune cells.
The next grant deadline is 1 April. For more details, visit www.immunology.org/grants-and-prizes.
24 EDUCATION & CAREERS
BSI Winter School
FUTURE FOCUS In December, the BSI held our Winter School in Nottingham. This event is tailored specifically to Immunology MSc students (and equivalent in other sectors), providing them with the opportunity to hear presentations from some of the UK’s leading immunology researchers and experience the atmosphere and benefits of a scientific conference. As well as a series of talks on a range of immunology topics specifically tailored for this audience, we had a careers session and a ‘Dragons’ Den’ session, where students had to work in groups to pitch their ideas for funding.
The event was sold out, with 150 delegates in total. On top of the scientific sessions, building networking skills was also high on the agenda, with the
majority of speakers staying for the whole conference to allow delegates to talk to them informally and find out more about what life as an immunologist is
really like. As one delegate commented, “It was a fantastic opportunity to meet current scientists, and provided an insight into life beyond a Master’s.”
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The winners of the ‘Dragons’ Den’ at Winter School
Immunology News | March 2019Immunology News | March 2019
26 JOURNAL NEWS JOURNAL NEWS 27
A round-up of new research published in the British Society for Immunology’s official journals Immunology and Clinical & Experimental Immunology. Members can access these journals free of charge at www.immunology.org/journals.
Immunology
Plasticity of antimicrobial and phagocytic programs in human macrophagesMacrophage (MΦ) polarisation is triggered during the innate immune response to defend against microbial pathogens, but can also contribute to disease pathogenesis. Previously, Montoya et al. had found that IL‐15‐derived classically activated macrophages (M1 MΦ) have enhanced antimicrobial activity, whereas IL‐10‐derived
alternatively activated macrophages (M2 MΦ) were highly phagocytic but lacked antimicrobial activity. Given that the ability to modulate MΦ polarisation from M2 MΦ to M1 MΦ may promote a more effective immune response to infection, they investigated the plasticity of these MΦ programs. Their data
demonstrate an approach to induce MΦ plasticity that provides the potential for re‐educating MΦ function in human mycobacterial disease to promote host defence and limit pathogenesis.
Montoya et al. 2019 Immunology 156 164–173 https://bit.ly/2TKK6u4
Clinical & Experimental Immunology
The BSI journals
Around the journalsImmune Update
A summary of some of the latest papers from the world of immunology. Written by Jennie Evans, Louisa James and Abi Pienaar.
Unmasking the master switch behind autoimmunity
Regulatory T cells play a critical role in modulating the immune system; if this system becomes unbalanced, T cells can attack the body’s own tissue, leading to devastating autoimmune diseases. Targeting the mechanism controlling this balance could lead to new treatments for these diseases, as identified through a collaborative effort from King’s College London and University College London. In the decade-long study, researchers identified the small molecule miRNA142 as a likely candidate, showing that genetically deleting the molecule from regulatory T cells in mice led to autoimmunity and death. Crucially, they were able to reverse the effect by using drugs that mimicked the actions of miRNA142 and rebooted the molecular pathway – restoring the mice to normal health. This research reveals how miRNA142 acts as a critical molecular ‘master switch’, controlling the actions of regulatory T cells. This has major implications for future drug development: turning up the dial of miRNA142 to promote anti-tumour T cells and treat cancer, or dialling it down to prevent autoimmunity.
Anandagoda et al. 2019 Journal of Clinical Investigation doi: 10.1172/JCI124725
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Broad range protection from vaccination
Vaccination is one of the most important preventative health interventions we have to stop the spread of infectious diseases. However, recent evidence indicates that the health benefits of vaccines may extend beyond this sphere, reducing all-cause mortality through non-specific alterations to innate immune cells. Typhoid fever, caused by Salmonella typhi, is a serious bacterial blood infection that kills over
120,000 people annually. Pennington et al. examined the effects, on the immune system as a whole, of vaccinating 16 adults with the live-attenuated oral typhoid vaccine Ty21a. They found changes within both the innate and adaptive immune systems. Monocyte phenotype and function were altered for three months while cytokine production, in response to a range of antigens, was altered for the
duration of the six-month trial. Although further studies are needed, these findings indicate that the Ty21a vaccine may have the potential to modify an individual’s susceptibility to a broad range of pathogens through an altered immune response.
Pennington et al. 2019 Science Advances 5 eaau6849 doi: 10.1126/sciadv.aau6849
Regulation of commensal bacteria is key for immune homeostasis; tipping the balance too far beyond either tolerance or inflammation leads to disease. Golebski and colleagues show that under steady state, airway epithelial cells are unresponsive to Pseudomonas aeruginosa or LPS despite expressing TLR4, suggesting that the airway epithelium tolerates Gram-negative bacteria by default. They discovered that airway epithelial cells express the IgG receptor, FcγRIII and opsonisation of P.aeruginosa with IgG converts the tolerogenic response to a pro-inflammatory response in a process dependent on cross-talk between FcγRIII and TLR4. FcγRIII is a low affinity receptor which requires immune complexes for activation. This discovery demonstrates how, during active infection, increased concentrations of IgG
CD5 and CD6 are related surface receptors that limit and promote T‐cell responses. Co‐stimulatory effects of CD6 depend on binding a cell surface ligand, CD166, and recruitment of the intracellular adaptor proteins GADS and SLP‐76 by C‐terminal phosphotyrosines. Breuning and Brown
have continued to identify interactions of CD5 and CD6 to understand their roles in T‐cell activation. In a screen to identify binding partners for peptides containing a cytoplasmic sequence they identified ERM proteins. Purified radixin FERM domain bound directly to CD5 and CD6 SDSDY peptides in a phosphorylation‐dependent manner at 37°. In human T‐cell blasts, mutation of the CD6 SDSDY sequence enhanced CD69 expression in response to CD3 monoclonal antibody.
In this proximal readout, interactions of the SDSDY sequence were dominant compared with the C‐terminal tyrosines of CD6. The data suggest that varying functional effects of CD6, and potentially CD5, depend on interactions of different cytoplasmic regions with the cytoskeleton and alter depending on the stimuli.
Breuning & Brown 2019 Immunology doi:10.1111/imm.13025 https://bit.ly/2TKL6yk
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Thorough understanding of the complex pathophysiology of osteoarthritis (OA) is necessary to open new avenues for treatment. Rosshirt et al. aimed to characterise the CD4+ T cell population and evaluate their activation and polarisation status in OA joints. Fifty‐five patients with end‐stage knee OA were enrolled. Matched samples of synovial membrane (SM),
synovial fluid (SF) and peripheral blood (PB) were analysed for CD3+CD4+CD8– T cell subsets and activation status. SM and SF samples showed a distinct infiltration pattern of CD4+ T cells. In comparison with PB, a higher amount of joint‐derived T cells was polarised into CD3+CD4+CD8– T cell subsets. Cytometric bead array analysis revealed significantly
increased immunomodulating cytokines in SF compared with PB. End‐stage OA knees are characterised by an increased CD4+ T cell polarisation towards activated Th1 cells and cytokine secretion compared with PB. This local inflammation may contribute to disease aggravation and eventually perpetuate the disease process.
Rosshirt et al. Clinical & Experimental Immunology doi.org/10.1111/cei.13230 https://bit.ly/2N1ptHk
A predominant Th1 polarisation is present in synovial fluid of end‐stage osteoarthritic knee joints: analysis of peripheral blood, synovial fluid and synovial membrane
Human cytomegalovirus (HCMV) is one of the most common human viral infections. While most people with the virus do not display any symptoms, it can cause serious effects in immunocompromised patients and in pregnant women, leading to congenital disability. Efforts to develop a vaccine against HCMV have not been successful to date, which has traditionally been assigned to the virus’s supposedly high mutation rate. Cudini et al. used a variety of sequencing, bioinformatic and modelling techniques to study the variability of the HCMV genome in blood samples from immunocompromised children. They found that the high levels of within-host HCMV nucleotide diversity were due to the frequent occurrence of mixed infections caused by genetically distinct strains, rather than a high mutation rate emerging from one strain. This finding is important in that it allows us to better understand HCMV evolution
and pathogenesis, showing that HCMV exhibits a similar mutation rate to other DNA viruses. Ruling out high mutation rate as a barrier to HCMV vaccine development also provides hope for a future breakthrough to prevent infection with this disease.
Cudini et al. 2019 PNAS doi: 10.1073/pnas.1818130116
HCMV mutation rate not as high as previously thought
A sequence conserved between CD5 and CD6 binds an FERM domain and exerts a restraint on T‐cell activation
Dendritic cells (DCs) are the key professional antigen‐presenting cells which bridge innate and adaptive immune responses, inducing the priming and differentiation of naive to effector CD4+ T cells, the cross‐priming of CD8+ T cells and the promotion of B cell antibody responses. DCs also play a critical role in the maintenance of immune homeostasis and tolerance. DC–T cell interactions underpin the generation of an autoimmune response
in rheumatoid arthritis (RA). In this new review, Wehr et al. describe the function of DCs and review evidence for DC and T cell involvement in RA pathogenesis, in particular through the presentation of self‐peptide by DCs that triggers differentiation and activation of autoreactive T cells. Finally, the authors discuss the emerging field of targeting the DC–T cell interaction for antigen‐specific immunotherapy of RA.
Wehr et al. 2019 Clinical & Experimental Immunology doi:10.1111/cei.13256 https://bit.ly/2WWkWdO
Dendritic cells, T cells and their interaction in rheumatoid arthritis
FcγRIII stimulation breaks the tolerance of human nasal epithelial cells to bacteria through cross-talk with TLR4
allow the epithelium to sense and respond appropriately through the coordinated activity of innate and adaptive receptors.
Golebski et al. 2019 Mucosal Immunology 12 425–433
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Immunology News | March 2019