BSI Congress 2019: Looking to Liverpool

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Immunology News | June 2019 A WORD FROM THE EDITOR 3 ©Shutterstock/Prokopenko Oleg Welcome to the summer edition of members working in all sectors of Immunology News. Activities at the BSI immunology. On pages 22–23, one of continue to move on apace and we have our Editorial Board members, Mihil been busy planning new activities to both Patel, discusses his recent move from support our members and represent academia to industry, examining the immunology on a wider stage. challenges and benefits of moving between Preparation for our 2019 Congress is different sectors and giving his top tips now truly underway and we look forward to to those considering such a move. welcoming many of you to Liverpool on 2–5 As well as supporting members in different December. One of the Congress highlights sectors, we aim to work with subject areas is always our Bright Sparks session which aligned to immunology to drive research takes place on the first afternoon of the event forward – you can read about our new and showcases the work of our brilliant early partnership with the National Cancer career researchers. In this issue, we hear Research Institute to address current from a past winner of the PhD category, challenges in immunotherapy on page 7. Tomas Castro, on his work on the role of IgG-mediated inflammation in patients Best wishes, with ulcerative colitis on pages 16–17. The BSI is always keen to support Jennie Evans The Team Contents Editorial Advisory Board: FEATURES: Edd James (Southampton) 14 Louisa James (London) An introduction to Donald Palmer (London) the British Society for Mihil Patel (Cardiff) Immunology Forum

Managing Editor: Antibodies pull the Jennie Evans 16 trIgGer in ulcerative Sub Editor: colitis Rebecca Ramsden Design: Qube Design Associates

British Society for Immunology 34 Red Lion Square London WC1R 4SG Tel: +44(0)203 019 5901 Email: [email protected] www.immunology.org The value of asking 18 questions: our 4 Society news Enquiries and correspondence: Parliamentary Jennie Evans: Questions Programme 22 Congratulations [email protected] 23 Future focus Advertising queries: Sarah Green: 26 Journal news [email protected]

Registered charity 1043255 in England Follow us: and Wales/SCD047367 in Scotland. Registered in England and Wales as britsocimm company 3009533. Set your alarm – 22 adjusting to life in britsocimm © 2019 British Society for Immunology industry The views expressed by contributors britsocimm are not necessarily those of the Society, nor can claims of advertisers britsocimm be guarenteed. The Society, Editorial Board and authors cannot accept britishsocietyforimm liability for any errors or omissions. british-society-for-immunology

Immunology News | June 2019 4 SOCIETY NEWS

VIEW FROM … Forum has achieved in the last few years, it really is staggering how far we’ve come. THE CHIEF And it doesn’t stop here; in fact, we’ve been turning up the temperature when EXECUTIVE it comes to engagement in Parliament, Whitehall and the devolved nations. Matthew What an action-packed few months it has Gibbard, our new Policy & Public Affairs been – time really has flown! As always, Manager, gives a great overview of some I’ve tried to get out and about as much as of the new elements of our programme to possible to meet our members and be at influence the powers that be to ensure the our events. I never cease to be amazed by best deal for UK immunology on pages 18– the quality of work that you are all doing and 20. We have lots more to come in this space your commitment and dedication to ever with plenty of opportunities for you all to get push the boundaries of knowledge through involved so do keep an eye out for more. the work that you do. And I for one am Thank you again for all of your ongoing thoroughly looking forward to BSI Congress support, I hope you enjoy reading another this year in Liverpool, our flagship event. You excellent issue of Immunology News can read more about Congress on pages and please keep up the great work! 7–8. It is guaranteed to be our best yet with the programme and speakers we have on With best wishes, offer! Plus 2018 was a non-Congress year elections (see page 5). A huge thank you so I’m sure that you’re all chomping at to them for joining the committees and to Doug Brown the bit to come together as the BSI family you all too for your nominations and votes Chief Executive, again (and I’m told the social elements are – this year we had the highest ever number British Society for Immunology just as good as the science…)! Please do of both of these which is fantastic – it’s Email: [email protected] sign up to attend and remember to submit so great to see such engagement from your abstract by 9 September 2019. you all. Your support for the committees Congress will also be a chance to meet enables them to continue to ensure the your BSI committee members, of which BSI remains relevant and impactful; do we have some new faces after this year’s read pages 14–15 to find out what the BSI

Your favourite research tools, improved BSI London Immunology Group with recombinant antibody technology. Barrier immunology 18 September 2019 Holiday Inn Bloomsbury, London, UK Abstract deadline: 19 July AB SEQUENCING | AB ENGINEERING | AB EXPRESSION | REAGENTS CATALOGUE Find out more: www.immunology.org/events Jo Revill absoluteantibody.com

Immunology News | June 2019 SOCIETY NEWS 5

SOCIETY NEWS New BSI committee members

Following our recent nominations call for positions on the BSI Board of Trustees and Forum, we are pleased to announce the following appointments. The turnout for this election was almost 20%. Congratulations to all the successful candidates and thank you to everyone who stood for election. Board of Trustees

ALLAN MOWAT DEBORAH DUNN-WALTERS COLIN DAYAN BSI Trustee BSI Trustee BSI Clinical Secretary and Trustee

Professor of Mucosal Immunology, Professor of Immunology, Clinical Professor, Cardiff University University of Glasgow University of Surrey Colin will join the Board of Trustees Allan is re-elected onto the Board and Deborah will join the Board of Trustees from January 2020. will commence his second term of from July 2019. office in July 2019.

Forum Find out more You can read the full candidate statement from each person in the members’ section of our website at www.immunology.org/new-committee- members. We welcome them all to the BSI and look forward to working with them to provide a strong voice for immunology.

FAITH UWADIAE FEDERICA VILLANOVA BSI Forum Early Career Representative BSI Forum Industry Representative

Postdoctoral Training Fellow, Francis Flow Cytometry Application Specialist, Crick Institute Miltenyi Biotec Limited

Faith will join our Forum in June 2019. Federica will join our Forum in June 2019.

Immunology News | June 2019 6 SOCIETY NEWS

SOCIETY NEWS Changes at Immunology

After 13 years at the helm, Danny Altmann is stepping down from his role as Editor in Chief of Immunology at the end of May. He has brought great vision and expertise to the journal, and has really made Immunology his own. It is with great sadness that we see him go. However, we’re pleased to announce that Simon Milling will be taking up the reins as our new Editor in Chief. Having served as a BSI Trustee since 2017, Simon has stepped down from the BSI Board to enable him to take up this new role with the Society. Simon’s first edition of the journal will be June 2019.

Danny Altmann's Arne Akbar, President farewell message: of the British Society for Immunology, said: “Having served from 2000 to “On behalf of 2005 as an editor the BSI, I would at Clinical & like to offer our Experimental gratitude to Immunology Danny Altmann and then from for successfully 2006 to 2019 as leading our Editor in Chief official journal, at Immunology Immunology, – a mind-boggling 19-year sentence on for 13 years. the night-shift for the BSI journals – the The journal has been in very capable time has come to stand down and focus hands. All his hard work and dedication on other challenges for the research has driven the journal forward and community. This has spanned a period of contributed to its 60-year legacy, immense change in immunology research, establishing it as a highly respected funding, publishing-business models and journal within the field. We wish him all competitor journals. It’s terrific to have the very best and every success for the ‘It’s terrific to have been around for such a strong period at future. the journals, to have helped publish some “Both of our official journals, been around for such really quite important immunology and to Immunology and Clinical & have had the privilege to get to know some Experimental Immunology, are crucial a strong period at the amazing, stellar, colleagues around the to the Society. The financial support journals, and to have world as editors.” they provide to us is used to benefit our members in the form of grants, travel helped publish some awards, Regional and Affinity group really quite important Simon Milling's introduction: meetings, our popular annual Congress and other key initiatives. I would like to immunology.’ “I am excited to encourage BSI members to continue join Immunology their support of our Society and join as Editor in Chief the many scientists contributing to the and to work with BSI’s journals with their research. Our official journals, Immunology the Editorial “I would like to give a warm welcome and Clinical & Experimental Team to help the to Simon Milling. Simon’s previous Immunology, are at the heart of our journal through involvement with the Society as a Society, with the aim of promoting the next stage of Trustee provides him with a unique and advancing immunology to foster its evolution. As perspective of BSI activities and I future innovation. Income from the some of you know, look forward to the next chapter of journals supports a significant part I am a mucosal immunologist and have Immunology with him as the new of the Society’s charitable activities, been working at the University of Glasgow Editor in Chief. As the income from our including our grant schemes and for the last 11 years. I have been actively two journals underpins the financial education and careers initiatives. involved with the BSI for the last few wellbeing of the BSI, he has an Society members receive free access years and was delighted both to stand for important role in the future success of to both journals via the BSI website. this position, and to receive enthusiastic the Society.” We encourage all BSI members to support in this from the journal’s Associate support our journals and consider Editor, Awen Gallimore. I have already submitting their work to our journals. received excellent support from Danny and the BSI’s publishing team to manage a smooth transition.”

Immunology News | June 2019 SOCIETY NEWS 7

SOCIETY NEWS BSI & NCRI announce new partnership

The British Society for Immunology is delighted to announce a new partnership with the National Cancer Research Institute (NCRI) to bring our two communities together to drive collaborations to address current challenges in immunotherapy through a series of joint initiatives. The NCRI and BSI plan to work together to establish a series of joint initiatives that aim to accelerate the progress of immunotherapy in cancer. This will include enhancing the training for researchers and promoting knowledge sharing, identifying the challenges currently hindering progress in cancer immunotherapy and the formation of strategic research groups to address key research questions. To launch this exciting new initiative, our President, Arne Akbar, reflects on the environment to promote the interaction history of research in the cancer immunology sphere and how we hope our new between researchers and clinicians in this collaboration will fuel innovative approaches to treating these diseases field to facilitate translational research activity. With this in mind, another strategic Immunology has flourished in recent results. By blocking the action of PD-1, goal is to interface our activities with years, with new discoveries of its intricate the immune system can be unleashed the pharma and biotech sector. This and elegant workings that allow us to to attack tumours. Allison and Honjo will ensure that the UK has the right understand its extensive reach into many won international recognition for this environment in terms of infrastructure, areas of health and disease. This new seminal work last year, sharing the investment and skills to allow research appreciation of how our immune systems Nobel Prize for Medicine in 2018. into cancer immunology to thrive. work to promote health and the varied Other areas of cancer immunotherapy We are therefore delighted to announce consequences when this process goes have hailed significant successes including our new partnership with the NCRI to bring awry places immunology at the centre the use of Ipilimumab (anti-CTLA4) the immunology research community and of research into many disease areas. in conjunction with Pembrolizumab cancer scientists and clinicians closer One of the most prominent of these (anti-PD-1) to treat melanoma and the together. Working together, we aim to is cancer. The first suggestion that the application of chimeric antigen receptor facilitate dialogue between the two groups immune system might play a role in (CAR) T-cell therapy to treat certain types to drive new collaborations that address treating cancer came as early as 1891 of leukaemia and lymphoma. However, challenges in immune-oncology and when the surgeon, William Coley, treated many trials that initially carried great advance understanding of the complex a patient who had a tumour on his tonsil hopes have identified unforeseen side- interactions between cancer and the by injecting it with bacteria and eliciting effects and some – such as sarcoma, immune system. Establishing these links to an immune response. The tumour began prostate or pancreatic cancer – appear speed up discovery in the clinical research to break down and the patient lived for resistant to immunotherapy approaches. space will enable fresh thinking to refine another eight years. More recently work There is therefore a lot of work still to be approaches to how the immune system led by Jim Allison and Tasuku Honjo on done to optimise cancer immunotherapy. can be harnessed to target individual the PD-1 protein that acts as a ‘brake’ A central ambition of the British Society cancers. Knowledge sharing will be a key on immune cells has yielded exciting for Immunology is to create the appropriate part of the initiative, allowing researchers

©Shutterstock/royaltystockphotos.com and clinicians from both communities to keep up to date with the latest data. With over 350,000 new cases of cancer diagnosed in the UK each year, it is imperative to move quickly to translate our endeavours into life-saving outcomes. Both we and our colleagues at the NCRI are committed to working together to achieve these aims through this initiative.

Arne Akbar President, British Society for Immunology

Find out more Keep an eye on our website for further updates on this initiative. If you have any queries, please email our Head of External Affairs, Jennie Evans at j.evans@ immunology.org.

Immunology News | June 2019 8 SOCIETY NEWS

SOCIETY NEWS BSI Congress 2019 2 – 5 December, Liverpool, UK Key dates The UK’s top immunology conference is back – bigger and better than before. Abstract submission: 9 September 2019

BSI Congress bursary applications: 11 October 2019

Early bird registration: 25 October 2019

Congress dates: 2 – 5 December 2019

Why you should attend? Keynote lecture - Cutting-edge science - Build your network Doreen Cantrell - Present your work Professor of Cell Biology and Immunology and Wellcome - Broaden your horizons Trust Principal Research Fellow, University of Dundee 17:30, Monday 2 December

Immunology News | June 2019 SOCIETY NEWS 9 ©Shutterstock/Ant Clausen

Plenary sessions announced Immunological challenges of controlling influenza Katherine Kedzierska (Melbourne, Australia) Peter Openshaw (London) Alain Townsend (Oxford)

Tissue resident memory T cells Donna Farber (New York, NY, USA) David Masopust (Minneapolis, MN, USA) Joint session Cancer immunotherapy with UK PIN Ana Anderson (Cambridge, MA, USA) 24 themed sessions The last day of the conference (Thursday Carl June (Philadelphia, PA, USA) 5 December) will be held jointly with Cornelius Melief (Leiden, Netherlands) including: the UK Primary Immunodeficiency Immune recognition of Network (UK PIN). We’re delighted to be running several joint sessions with The recognition and clearance of microbiota species senescent cells by leukocytes them, including two plenaries and parallel sessions on autoimmunity and Arne Akbar (London) B cell activation and pattern recognition in inflammation. Valeria Krizhanovsky (Rehovot, Israel) differentiation

Learning from cell signalling Inhibitory immune receptors in immunodeficiency and new immunotherapies Ulf Klein (Leeds) Klaus Okkenhaug (Cambridge) Sonal Srikanth (Los Angeles, CA, USA)

Mechanism of inflammation Find out more in immunodeficiency www.bsicongress.com Sophie Hambleton (Newcastle) @bsicongress Andrew Snow (Bethesda, MD, USA) ©Shutterstock/Shahid Khan

Immunology News | June 2019 10 SOCIETY NEWS

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Immunology News | June 2019

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SOCIETY NEWS

Immunology Teaching Award

IUIS2019 registration still open Registration is still open for the 17th International Congress of Immunology taking place in Beijing, China on 19–23 October 2019. This is the largest global event in immunology and a great opportunity to hear from some of the leading international experts in the field. For more information and to register, visit https://iuis2019.org.

Congress committee update

We are delighted to welcome two new members, Alex Spencer (Oxford) and John Tregoning (London) to our Congress Committee. This committee is responsible We’ll soon be launching the call for education, along with the communication for the planning and delivery of the BSI’s nominations for our 2019 Immunology skills to make these complex subjects flagship event, BSI Congress, which takes Teaching Excellence Award to highlight accessible to their students. We’re looking place two out of every three years. Our some of the outstanding immunology for exceptional communicators who are grateful thanks go to our two outgoing teachers based in UK higher educational able to inspire the next generation of committee members, Andrew Godkin institutes. The award rewards those who immunologists. Check out our website for (Cardiff) and Luke Foster (Birmingham) for show a passion for immunology and further details. all their hard work while on the committee.

UPCOMING BSI Regional and BSI West Midlands Group & Affinity Groups University of Birmingham BSI MEETINGS DISCOVERY TO CLINICAL We have lots of upcoming meetings BSI Ulster Immunology Group APPLICATIONS OF REGULATORY covering a vast array of immunological IMMUNOLOGY WITHOUT BORDERS T CELLS IN AUTOIMMUNITY 13–14 June 2019 AND TRANSPLANTATIONS topics. Find out more at Belfast, UK 11 July 2019 www.immunology.org/events. Birmingham, UK BSI Greater Manchester & BSI meetings Wessex Immunology Groups BSI London Immunology Group BRITISH SOCIETY FOR TYPE 2 IMMUNOLOGY BARRIER IMMUNOLOGY IMMUNOLOGY CONGRESS 2019 24 June 2019 18 September 2019 2–5 December 2019 Manchester, UK London, UK Liverpool, UK BSI Histocompatibility &

©Shutterstock/Shaun Jeffers Immunogenetics Group BRITISH SOCIETY FOR BSI supported meeting HISTOCOMPATIBILITY Co-hosted with British Society for & IMMUNOGENETICS Immunology ANNUAL CONFERENCE VALIDATE SCIENTIFIC CONFERENCE 26–27 June 2019 2–3 October 2019 Leicester, UK London, UK

Immunology News | June 2019 12 SOCIETY NEWS

SOCIETY NEWS New review series: Vaccines for emerging pathogens

Clinical & Experimental Immunology is pleased to present part 1 of our new two- ©NIAID/Flickr CC- BY 2.0 part Review Series ‘Vaccines for emerging pathogens: from research to the clinic’ (guest editor: Diane Williamson, Defence Science and Technology Laboratory, Porton Down, UK). The Review Series is freely available to read and download.

This topic has been brought into sharp vaccine development. Morici et al. focus in recent years following significant address progress in the development outbreaks of viral diseases such as those of vaccines for melioidosis, a bacterial causing severe acute respiratory syndrome disease which causes an estimated and Middle East respiratory syndrome, 165,000 human cases per year. as well as devastating outbreaks of New technologies for vaccine formulation diseases caused by the Ebola, Marburg, and administration are necessary in the Zika and Lassa fever viruses, to name context of rapid vaccination on a large only a few examples. Additionally, scale. Wallis et al. review novel approaches bacterial infections leading to bubonic for the design, delivery and administration and pneumonic plague, most notably in of vaccines, discussing a range of vaccine Madagascar in 2018, as well as malaria formulations, presentations and parenteral in many tropical countries, melioidosis in administration routes. Miquel-Clopes et south east Asia and tularaemia in northern al. focus on vaccines that are designed Europe and North America, have incurred to induce mucosal immunity to protect significant morbidity and mortality. mucosal surfaces from pathogen invasion. Review Series: https://bit.ly/2vTxYwu In our Review Series, the life cycle of Where new vaccines are required under Afrough et al. these pathogens and the epidemiology emergency conditions, it is essential for https://doi.org/10.1111/cei.13295 of disease have been reviewed in the developers and manufacturers to work Sharpe et al. context of potential points of intervention closely with the regulatory authorities https://doi.org/10.1111/cei.13292 for the prevention of human infection. and with the WHO to understand the Morici et al. Afrough et al. review a range of emerging requirements to bring a candidate vaccine https://doi.org/10.1111/cei.13286 viruses and make the case for applying as quickly as possible through development Wallis et al. molecular techniques to understand and into the clinic. This Review Series https://doi.org/10.1111/cei.13287 viral pathogenesis. Sharpe et al. tackle evidences the progress being made in Miquel-Clopes et al. how we understand the interaction of the vaccines for emerging pathogens. https://doi.org/10.1111/cei.13285 host with a viral pathogen to expedite BSI at the Big Bang Fair On Saturday 16 March, the BSI took part in the Big Bang Fair at Birmingham's National Exhibition Centre – a day of science exploration aimed at families. Throughout the day, BSI staff and volunteers delivered a range of activities focussed on vaccines and herd immunity. These included making plasticine antibodies and microbes, explaining antibody specificity using a magnet game and a herd immunity tombola! Overall, more than 2,000 people visited the BSI’s stand and we were delighted to able to spread knowledge of how vaccines work and why they are important. You can read more about the event on our blog where one of our volunteers, Ilaria Chicca, has written about the experience: http://bit.ly/2JKIHT1.

Immunology News | June 2019 SOCIETY NEWS 13

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Immunology News | June 2019 14 FEATURE ARTICLE

An introduction to the British Society for Immunology Forum

The BSI Forum is our 'think tank' and the place where issues and ideas are raised, What does being a member discussed and developed for the consideration and approval of the Board of of Forum involve? Trustees. These relate to education and careers, public engagement, policy and As well as attending the quarterly meetings, public affairs, as well as communications. The role of Forum is to help the Society Forum members also undertake an array of in implementing its current strategic plan by providing a mechanism by which the tasks for the Society, including representing us at various events. Examples of these voice of the membership can be fed into new activities. include:

How does Forum operate? Parliamentary engagement Forum members are elected to represent a Recent achievements Rebecca Newman (Early Career section of the BSI membership. Their role Professor Anne Cooke recently finished Representative) attended the Royal Society is to put forward the views of the sector her term of office as Chair of Forum, of Biology ‘Voice of the Future’ event at they have been elected to represent, as a position she held from 2014 to 2018. the Houses of Parliament for early career well as their own thoughts. Currently there During this time and under Anne’s researchers to ask questions of senior are 18 elected members covering early dynamic and enthusiastic leadership, members of Parliament in a committee career researchers, clinical and veterinary Forum developed and inputted to several setting. Becky agreed that is was important immunologists as well as national BSI strategies – in particular to increase for the BSI to engage with parliamentarians representatives from England, Northern support and representation for early through schemes such as this to ensure Ireland, Scotland and Wales. My role as career researchers within the Society – that the BSI keeps raising important issues Chair of Forum is to lead discussions which have been approved by the Board through multiple channels. and also to feed back the thoughts of and put into practice. These include: Anne Cooke (past-Chair), Helen McGettrick Forum to the Board of Trustees. (England Representative) and Fane Mensah Forum meets four times a year in 1. Creating two new positions on the Board (PhD Representative) attended the ‘Future London when elected members work with of Trustees for early career researchers of Immunology’ event at the Houses of BSI staff on all aspects of the Society’s – Calum Bain and Emma Chambers were Parliament last year. This was a joint venture work and current strategy. Items on elected to these positions last year delivered in partnership by the BSI, AbbVie, the agenda are varied and range from Bioindustry Association and National how to increase diversity and inclusion 2. All parallel sessions at BSI Congress Rheumatoid Arthritis Society and hosted by at BSI meetings, to developing ideas to be co-chaired by an early career Grimsby Labour MP, Melanie Onn, who has for communicating with the public, and researcher onwards an interest in inflammatory diseases. responding to questions from expert panels in science, health and Government. 3. Advising on the BSI Careers Review ‘You need to be Forum members are also invited to conducted in 2017, both in terms of represent the BSI at external events. identifying what areas it should cover passionate about You don’t need to be an expert in and evaluating the final report to develop all branches of immunology to be a proposals for future careers support by supporting the member of Forum. However, you do the BSI immunology sector need to be passionate about supporting and investing in the immunology sector 4. Providing feedback and advice on setting so that it can continue so that it can continue to advance up the BSI mentoring scheme, which excellence in immunological research, commenced in 2017 (initial training provided to advance excellence scholarship and clinical practice in order and mentoring available for one year) to improve human and animal health. in immunological 5. Developing ideas and content for research, scholarship the Early Career Training Day aimed at postdocs, which was launched in and clinical practice to December 2018 improve human and 6. Advising on establishing an Industry animal health.’ Representative position on Forum Immunology News | June 2019 FEATURE ARTICLE 15

Alice Burton Ann Ager Chair Anne Cooke Arne Akbar Ceri Fielding Donald Davidson

‘I have joined an energetic group of people keen to share and discuss ideas and views on the future of immunology.’ Elma Tchilian Fane Mensah Helen Collins

Helen McGettrick Laura Pallett Matthew Buckland Megan Macleod Sofia Grigoriadou Federica Villanova

Find out more If you would like to find out more about the work of the BSI Forum, please email [email protected].

Faith Uwadiae Antony Psarras Louise Cosby Rebecca Newman

Policy and public affairs Education and careers led by welcome to our newly elected members All members have the opportunity of the Education Secretary of Forum who are: Faith Uwadiae (Early inputting to BSI responses to policy Our Education Secretary, Helen Collins, Career Representative) and Federica consultations from Parliament. These along with three of our Early Career Villanova (Industry Representative). include select committee consultations and Representatives, Fane Mensah, Rebecca I have only been in post as Chair of All Party Parliamentary Group enquiries, Newman and Laura Pallett, ran a well- Forum since January this year but it did which request evidence and expert views attended session at BSI Congress not take me long to realise that I have on topics ranging from the Life Sciences 2017 to discuss the findings of the BSI joined an energetic group of people Industrial Strategy to Brexit (of course!). Careers Report with the membership keen to share and discuss ideas and and gain their feedback to help us in the views on the future of immunology. The Equality, diversity and inclusion development of future careers activities. fact that Forum makes a difference is We are developing proposals for how the evidenced by its recent achievements. BSI can support equality, diversity and Exploring international links with I hope after reading this that you will inclusion throughout its activities and in the other immunology societies be encouraged to stand for Forum in wider immunology sector. The Forum was Laura Pallet, (Early Career Representative) the future. Spot a Forum member you consulted during BSI policy development on attended the Chinese Society for already know from the photo gallery ways to support members throughout their Immunology’s Annual Congress in to find out more about Forum. It is a career. Shanghai and visited the Key National great opportunity to gain experience in Laboratory of Medical Immunology. those all-important life skills such as Public engagement led by the Laura was able to contrast and committee work, networking and public Public Engagement Secretary compare life as an ECR with her outreach. Besides, it gets you away During her time on Forum, Early Career peers and gain insight into academic from your day job for a few hours and Representative Emma Chambers trained and clinical immunology in China. you can leave your mark on the BSI! to be a BSI Vaccine Ambassador in our pilot Election to Forum scheme and went into parent and baby Ann Ager groups to discuss how vaccines work and On behalf of Forum I would like to say Chair of Forum and Trustee, answer parents’ questions on immunisations. congratulations and give a very warm British Society for Immunology

Immunology News | June 2019 16 FEATURE ARTICLE Antibodies pull the trIgGer in ulcerative colitis

The winner of our Bright Sparks PhD session at the BSI Congress in 2017 was Tomas Castro from the University of Cambridge with his talk entitled ‘Anti- commensal IgG augments intestinal inflammation in ulcerative colitis via IL- 1beta-dependent Th17 immunity’. Here, Tomas tells us more about his research on unravelling the role of IgG-mediated inflammation in patients with ulcerative colitis. Tomas Castro receiving his 'Bright Sparks in Immunology' award from BSI Education Secretary, Helen Collins

A healthy lifestyle is all about balance; components of the microbiome lead to a exclusion’). This function is essential be it professional, emotional, nutritional spectrum of disorders collectively known in preventing intestinal invasion by or immunological. A vigorous as inflammatory bowel disease (IBD). opportunistic microorganisms. However, immune response is required to fight Incidence of the two major subtypes of IBD the assumption that intestinal humoral malignancies and the multitude of – Crohn’s disease (CD) and ulcerative colitis immunity is all about IgA has been called microbes that seek to invade us, but (UC) – is increasing globally alongside into question by genetic studies implicating these responses are tightly regulated Western lifestyles and causes significant a variant of FcγRIIA, an activating receptor to suppress overt immunity and return morbidity and cancer-associated mortality. for IgG, with susceptibility to UC. us to homeostasis. This immunological A dysregulated immune response is at Potency of IgG antibodies Goldilocks zone is exemplified in the dual the heart of IBD. Intense research has nature of many (if not most) immune focused on pathogenic T cells, informed Unlike IgA, IgG antibodies are potently cell subsets, from effector versus by seminal animal and genetic studies inflammatory – they exhibit complement- regulatory T cells to ‘M1’ versus ‘M2’ that implicate the IL-23–Th17 axis as fixing activity and can engage cell macrophages, all acting in concert to a common contributor to both CD and surface Fcγ receptors (FcγRs), leading mount appropriate immune responses. UC susceptibility. In this setting, innate to immune cell activation. This leads In the gastrointestinal tract, maintaining immune cells, such as macrophages and us to two unsurprising observations: 1) immunological balance is particularly dendritic cells, integrate poorly defined IgG-FcγR signalling is associated with key. The gut is colonised by trillions triggers that drive IFNγ- and IL-17- numerous inflammatory and autoimmune of commensal microorganisms (our producing T cells through the production disorders, such as rheumatoid arthritis microbiome), with essential roles in of key cytokines, including IL-23 and and systemic lupus erythematosus, and nutrient salvage, pathogen exclusion IL-1β. These discoveries have driven 2) IgG is almost entirely excluded from and immune education. However, a clinical revolution, with monoclonal the healthy adult gut. How could this the gut represents a major mucosal antibodies targeting these cytokines receptor influence disease susceptibility entry point for pathogens, requiring showing therapeutic promise in IBD. in an IgA-dominated organ? the immune system to be primed to In contrast to T cells, whether and how This was the question I began trying respond to invasive microorganisms B cells and the humoral immune response to answer in 2014 when I joined Dr that breach the intestinal epithelium. are altered in IBD is poorly understood. Menna Clatworthy’s lab (University of Immunoglobulin (Ig)A is a well-known Cambridge) as a PhD student, the result IBD – dysregulation of the immunological cornerstone of intestinal of which I was fortunate to present at immune response health. IgA, produced by intestinal plasma the 2017 BSI Congress in Brighton. In certain individuals, a complex cells, is a predominantly non-inflammatory We had a simple hypothesis – that interaction of environmental and genetic class of antibody secreted into the gut immune dysregulation in IBD leads to the factors results in the breakdown of lumen where it binds to commensal emergence of pathogenic IgG that can the rules governing intestinal health. microbes and keeps them away from the drive disease. We began by profiling IgA Exacerbated immune responses towards epithelium (a process known as ‘immune and IgG binding to commensal microbes

Immunology News | June 2019 FEATURE ARTICLE 17 in stool samples, and made the rather In vivo studies in DSS mouse model response was pathogenic, as treatment remarkable observation that up to 80% As interventionist human studies are with a blocking IL-1 receptor monoclonal of intestinal microbes from UC patients very difficult to perform, we turned to antibody effectively suppressed intestinal were coated in IgG. This was most evident an in vivo mouse model of IBD, dextran inflammation. In contrast, macrophage- in individuals with severe disease, where sodium sulfate (DSS)-induced colitis, specific overexpression of FcγRIIB was the levels of IgG and IgA binding were to investigate the contribution of our in disease-protective relative to control mice, equivalent, whereas IgG was almost vitro-defined mechanism to intestinal directly implicating the FcγR-macrophage- entirely absent in healthy controls. inflammation. Similar to IBD patients, IL-1β axis as a major disease mediator. DSS-exposed mice exhibited a local IgG Utilising transcriptomics Last piece of the puzzle response towards commensal microbes, Having identified macrophages as and elevated IL-1β production by colonic Given this strong IL-1β effect, the last the major source of intestinal FcγRIIA macrophages. Importantly, passive piece of the puzzle was to define how expression, we set out to define how transfer of anti-commensal IgG to naïve this FcγR network influenced local T cell IgG-mediated activation of these cells animals was enough to enhance disease activity, a cell type heavily implicated in IBD may contribute to IBD. For this, we are activity and increase colonic macrophage susceptibility. We demonstrated an IL-1β- thankful that IBD research is greatly IL-1β production, demonstrating a direct dependent increase in IL-17A production facilitated by the wealth of transcriptomic pathogenic role of IgG in the gut in vivo. by colonic CD4+ T cells and γδ T cells in datasets deposited in free-to-access public The FcγRIIA variant implicated in FcγRIIB-deficient mice, while macrophage- repositories, aided by the relative ease protection from UC encodes a receptor specific FcγRIIB overexpression was with which clinicians can directly sample with reduced IgG affinity. To mimic the enough to suppress this response. All diseased tissue by endoscopic biopsy. Using effect of this variant in vivo, we made use together, our work delineated a mechanism this data as a starting point, we identified of transgenic mouse strains with graded whereby FcγR signalling in colonic IL-1β as the dominant inflammatory activating FcγR signalling due to absent or macrophages induced a pathogenic IL-1β cytokine elevated in inflamed UC mucosal elevated expression of the sole inhibitory response, which in turn mediates activation biopsies, and found it to associate very FcγR, FcγRIIB, the latter specifically of an IBD-associated T cell response, closely to FcγRIIA, ultimately attributable in macrophages. This was necessary causing inflammation and disease. to their co-expression within intestinal as mice lack FcγRIIA itself but express We were pleased to have our study macrophages. Importantly, we were able other functionally homologous FcγRs. published recently1 but many unanswered to show that FcγRIIA signalling could drive Exacerbated FcγR signalling in questions remain. The most pertinent NLRP3-dependent IL-1β production, an FcγRIIB-deficient mice resulted in being whether we can target FcγR effect modulated by FcγRIIA genotype, augmented intestinal disease activity and signalling therapeutically in IBD. Time potentially linking IgG and FcγRIIA to elevated macrophage IL-1β expression. and clinical trials will be required to mucosal inflammation in IBD via IL-1β. Importantly, this augmented IL-1β test the potential of this pathway as a therapeutic target, but one thing is

Tomas Castro-Dopico Postdoctoral Researcher, Molecular Immunity Unit, Department of Medicine, University of Cambridge

REFERENCES 1. Castro-Dopico et al. 2019 Immunity 50 1099–1114 https://bit.ly/2IMk8nm Could you be the next Bright Spark in Immunology? Bright Sparks in Immunology is our event to showcase the work of PhD students and early career postdocs who are submitting an abstract for Congress. To enter your abstract, just tick the relevant box on the abstract submission form for BSI Congress. If your abstract is chosen, you will be invited to present your work at this year’s Bright Sparks session, which will take place on the afternoon of Monday 2 December at the BSI Congress in Liverpool. For more information, please visit www.bsicongress.com. 18 REPRESENTING IMMUNOLOGY The value of asking questions: the BSI Parliamentary Questions Programme ©UK Parliament/WikiMedia CC BY-3.0

As part of our Policy and Public Affairs Plan, we have launched an ambitious Parliamentary Questions Programme designed to raise the profile of both the issues we campaign on and the BSI itself within Parliament, Government and the wider policymaking sphere. In keeping with the interrogative theme, here’s a Q&A guide to what this means and how it will benefit immunology and the BSI.

What are Parliamentary questions? Parliamentary questions are asked by backbench Members of Parliament to Government Ministers about their ministerial responsibilities and around 20 names that are placed on the these are published three sitting days departmental business. They are used agenda (called the order paper). In order ahead of when they will be asked in the to elicit information from and scrutinise to ensure party political balance, the Commons chamber, so the Minister will policymaking of the Government. There Speaker will choose some MPs on the know these in advance and will have had are two types of parliamentary question: day to ask questions in between those the opportunity to prepare a response and oral questions and written questions. listed on the order paper, so it alternates seek any research or guidance needed from Oral questions: every five weeks that between Members on the Government the appropriate civil servants. Each MP who the House of Commons meets, each benches and the opposition benches. asks a substantive question will, after the ministerial team running each Government Minister’s answer, be offered the opportunity Do Government Ministers know department must appear in the Commons to ask a supplementary question on the chamber to answer questions that are the questions in advance? same topic. The Minister will have had no asked in person. The most well-known The questions submitted to the shuffle advance warning of this supplementary oral question session is Prime Minister’s are known as substantive questions and question and so must be well briefed Questions, which are an exception to the five-week rule and have been held weekly on a Wednesday at 12:00 since 2003. Example question to the Home Office: Written questions: backbench MPs may Question from Ben Lake MP to the Home Office: submit them at any time either via an online form on the parliamentary intranet or via To ask the Secretary of State for the Home Department, what assessment he has hard copy at the House of Commons Table made of the potential merits of extending international students’ post study leave Office, and the Minister responsible will period to find permanent skilled work. respond usually within a week or two. They Response from Rt Hon Caroline Nokes MP, Minister of State for Immigration: can be more specific than oral questions and can receive more detailed answers. In 2017, the Home Office commissioned the independent Migration Advisory Both oral questions and written questions Committee (MAC) to provide an objective assessment of the impact of international and their answers are published in students in the UK for the first time. Hansard, the Official Report of the House. In line with the MAC recommendations, we announced in the Immigration White Paper published in December 2018 that we will increase the post-study leave period Who chooses who asks for postgraduate students to six months, and doctorate students to a year. We will also the oral questions? go further, by increasing the post-study leave period for all undergraduates studying MPs are allowed to submit one oral at institutions with degree awarding powers to six months. question written in advance for which These changes will benefit tens of thousands of students and will help ensure that our they are entered into a ballot called world-leading education sector remains competitive globally. ‘the shuffle’, which will randomly draw

Immunology News | June 2019 REPRESENTING IMMUNOLOGY 19

‘We identify MPs who are interested in a topic in our agenda and email them all with suggested questions ahead of a particular department’s questions and explain why what we are suggesting is so pressing.’ enough on the topic to be able to think on their feet and provide a response. (In Example question to BEIS: practice however, MPs in the Government Question from Jim Shannon MP to Department for party will often let the Minister know the Business, Energy & Industrial Strategy: supplementary question in advance too as they are normally trying to get the most To ask the Secretary of State for Business, Energy and Industrial Strategy, whether helpful and fullest response possible, unlike the £7 billion of additional spending for research and development will be in addition an opposition MP who is more likely to be to replacing EU funding lost after the UK leaves the EU. trying to catch the Minister off guard). Response from Chris Skidmore MP, Minister of State for Universities, What is the BSI Parliamentary Science, Research & Innovation: Questions Programme? At Spending Review 2015, the Government protected science funding, committing to We identify MPs who are interested in a invest £26.3 billion between 2016-21, and has since committed to an additional £7 topic in our agenda and email them all with billion by 2021-22 – the largest increase ever. The terms of the Withdrawal Agreement, suggested questions ahead of a particular if ratified, would provide for continued UK participation in EU Programmes, department’s questions and explain why including Horizon 2020, to December 2020 and for the lifetime of projects under the what we are suggesting is so pressing. programme. If an agreement is reached, projects approved during this period will be able to continue with an uninterrupted flow of EU funding. If we leave the EU without a ©Shutterstock/Dafinka deal in place, the underwrite guarantee and extension are Government commitments to provide funding required for the UK to participate in Horizon 2020 until the end of 2020 and for the lifetime of projects. In this scenario, HM Treasury will provide additional funding on top of existing departmental budgets – further demonstrating the Government’s commitment to the UK’s world-class research base.

What departments have written parliamentary questions asked for we targeted? us to all four departments we have targeted We have asked MPs to ask questions to by 10 MPs from five different parties the Department for Health and Social (Conservative, DUP, Labour, Plaid Cymru Care on vaccines; to the Department for and SNP). You can see a couple of examples Business, Energy and Industrial Strategy of written questions that MPs have on UK and EU science funding; to the submitted on our behalf in the side boxes. Home Office on the importance of our What are the benefits of doing this? immigration system allowing the UK to attract talent from around the globe; Apart from allowing us to receive answers and to the Department for Education on from Government Ministers about issues getting more students into STEM education that concern and affect the BSI and its and increasing diversity within STEM. members, it allows us to build relationships with MPs. The objective being that eventually Does anyone else do this? we will have a network of parliamentarians Yes, we are competing for MPs’ attention with whom we work closely to raise matters with a multitude of other organisations. that are important to us and can influence This includes their own parties – Ministers’ Government policy on our behalf. It also and Opposition frontbenchers’ aides raises our profile as a leading scientific will try to persuade backbench MPs society and puts the topics we care about to ask planted questions to highlight on the agenda and in the public eye. Government strengths or to underline their weaknesses, respectively. Matthew Gibbard Policy & Public Affairs Manager, Have we had any success? British Society for Immunology At the time of writing, the Parliamentary Email: [email protected] Questions Programme has been running for about two months. In that time, we have had three MPs submit oral questions, with one winning the ballot and also asking our suggested supplementary question in the Commons chamber. We’ve also had 27

Welcome to our new regular update on the BSI’s policy and public affairs work to highlight the programme of activities we undertake to advocate for immunological science and health to the Government, parliamentarians and policymakers.

Parliamentary Questions Those of you who have read the article detailing our new Parliamentary Questions Programme will know that we have been suggesting questions for backbench MPs, whose interests overlap with the BSI’s policy agenda, to ask Government Ministers. At the time of writing, we’ve had a good level of success in parliamentarians taking this up in the first two months of activity. We’ve had 27 written questions tabled on our behalf to all four Government departments we were targeting, by 10 MPs, from five different as an integral part of its five-year action MP (Con, Newton Abbot) who chairs the political parties. These have been helpful plan to tackle AMR and committed to All Party Parliamentary Group (APPG) almost without exception, either getting on ‘[providing] the money that is necessary’ on Medicines and Medical Devices and the record that the Government is planning to tackle AMR. To watch the full Chris Green MP (Con, Bolton West) who actions that align with our agenda or exchange, visit https://bit.ly/2Ijfr4X. chairs the APPG on Medical Research identifying an area requiring more scrutiny. and serves as Vice-Chair of the APPG Informing the debate An example of the former was Chris for Life Sciences. We are hoping that Skidmore MP (Con, Kingswood), the The next day, on 28 March, a Westminster these will be productive discussions Higher Education Minister, confirming Hall debate was held to discuss World around the challenges facing immunology to Bob Blackman MP (Con, Harrow East) TB Day and efforts to end tuberculosis today and will allow for the beginning of that the Government would be seeking globally. (A Westminster Hall debate occurs some fruitful working relationships. to increase the number of international in the Commons’ lesser known secondary Next on the agenda students studying in the UK by over a third chamber and with the crucial difference that – to 600,000 by 2030, despite its retention debates are led by backbenchers seeking The BSI is putting together a response of the net migration target. An example ministerial responses on issues important to the recently announced Government of the latter category has been a couple to them, rather than the Government consultation on ‘the design of UK funding of responses to Rosie Cooper MP (Lab, setting the agenda). The BSI prepared and schemes for international collaboration, West Lancashire) regarding the training distributed a briefing on the importance of innovation and curiosity driven blue skies of healthcare professionals on vaccines funding research to develop a vaccine to research’, led by Professor Sir Adrian that don’t fully align with each other, and protect against pulmonary TB in adults, and Smith. We will bring you more news on this we plan to follow this up for clarification the contribution that drug-resistant TB is in the next issue of Immunology News. with the new Public Health Minister, making to global AMR. We were pleased that As always, we are keen for BSI members Seema Kennedy MP (Con, South Ribble). a number of MPs used our briefing including to get involved in our policy and public Our first success in oral questions Jim Fitzpatrick MP (Lab, Poplar and affairs work. If you wish to raise any issues came on 27 March when Rt Hon Stephen Limehouse) who namechecked the BSI, and that you have encountered with us, or if you Crabb MP (Con, Preseli Pembrokeshire) Nic Dakin (Lab, Scunthorpe) who highlighted want to write to your own MP but need some questioned Health and Social Care that TB hotspots exist here in the UK in more information to get started, please do Secretary, Rt Hon Matt Hancock MP (Con, London, Leicester, Luton, Birmingham, contact me at [email protected]. West Suffolk) with two of our suggested Manchester and Coventry. To read the questions on the role that vaccines have full debate, visit https://bit.ly/2YsQeKc. Matthew Gibbard in combating the threat of antimicrobial Policy & Public Affairs Manager, Building our influence resistance (AMR) to antibiotics. In his British Society for Immunology answers, the Health Secretary commented Coming up, we have face-to-face meetings that the Government is using vaccines planned in May with Anne-Marie Morris

Immunology News | June 2019 MEMBERS’ ACHIEVEMENTS 21

Congratulations to new Fellows Congratulations Both the Academy of Medical Science and the Royal Society have announced This is the section of the magazine where we celebrate the their lists of new Fellows for 2019. achievements of our members. Our congratulations to all who Congratulations to the following BSI are mentioned here. members on being elected as Fellows in recognition of their outstanding contributions to the discipline. Ronald Ross Medal Travel grant success Royal Society The following members were recently Our congratulations to Eleanor Riley (Roslin Charles Bangham, Chair of Immunology awarded BSI travel grants: Institute) who has been awarded the Ronald and Head of the Division of Infectious Ross Medal. This medal is only awarded Diseases at Imperial College London. Sabha Asghar, Carly Bliss, William every three years and recognises outstanding His work examines the virology Branchett, James Cameron, Fiona contributions to the advancement of and immunology of persistent virus Carty, Alistair Chenery, Joe Chouhan, tropical public health or tropical medicine. infections, with particular focus on the Sally Clayton, Mathew Clement, Megan Professor Riley is a world leader in malaria human T-cell leukaemia virus (HTLV- Cole, Cherrelle Dacon, Guillaume immunology, with a unique background 1). His contributions to the discipline Desanti, Natalie Edner, Jonathan in basic sciences, veterinary medicine, include discovering the virological Holbrook, Daniel Johnston, Tariq human infectious diseases and global synapse – how viruses such HTLV-1 are Khoyratty, Taewoo Kim, Max Kirtland, health, and has made major contributions to transmitted between cells. Layal Liverpool, Rikah Louie, Ruairi strengthening research capacity in Africa. Caetano Reis e Sousa, Assistant Lynch, David Malone, Elizabeth Mann, Research Director and Senior Group Dyana Markose, Stefania Martin, Brian Leader, Francis Crick Institute. His McHugh, Michelle Naughton, Christina work involves studying the mechanisms Nikolakopoulou, Lilian Nwosu, Communicating used by the immune system to sense Hannah Prendeville, Michael Ridley, infection, cancer and tissue injury, Sheree Roberts, Aoife Rodgers, Silvia Immunology with a particular focus on the role of Rosini, Helene Stern, Steve Webster, dendritic cells. Carissa Wong and Louise Yindom. Grants Academy of Medical Sciences The next application deadline is midday, Siân Faustini and colleagues from the Clare Lloyd, Professor of Respiratory 1 August 2019. More information at University of Birmingham will host a Immunology and Wellcome Senior www.immunology.org/grants-and- half day of games and craft for 9–11- Fellow at Imperial College London. prizes/travel-awards. year olds focusing on how the immune Her work examines the molecular system works, how infectious diseases mechanisms that underlie common lung spread and how vaccines confer diseases, such as asthma or fibrotic protection. Shona Moore and colleagues lung diseases. from University of Liverpool will run Helen McShane, Professor of Summer an activity at Bluedot Music Festival at Vaccinology and Deputy Departmental the Jodrell Bank Observatory in July to Head at University of Oxford. Her work Placement simulate the outbreak of an infectious looks at tuberculosis vaccinology, disease – through use of stickers, and in particular studying the safety, Award Scheme how a vaccine can halt transmission. immunogenicity and efficacy of candidate This BSI scheme supports early career Lisa Whittaker and colleagues from TB vaccines through clinical trials. scientists to conduct extended placements Cardiff University and Tenovus Cancer Alison Simmons, Professor of in labs other than their own. Recent Care will produce a 2–3-minute virtual Gastroenterology at the MRC Human awards are: reality experience showcasing T-cells Immunology Unit, University of William Mirfin-Boukouris (Keele and their role in the immune system and Oxford. Her research focuses on University) to determine whether brain fighting cancer. This will be premiered defining innate immune pathways that immune cells show altered inflammatory at the Merthyr Tydfil Science Festival underpin digestive diseases, such as profiles when exposed to ‘stealth’ coated and in July. Finally, Ines Diaz del Olmo inflammatory bowel diseases, Crohn's ‘control’ nanoparticles. and colleagues from The University of disease and ulcerative colitis. Samantha Jones (Cardiff Metropolitan Manchester work with SHE Choir to run University) who will investigate the a singing workshop at Bluedot Music immunomodulatory functions encoded by Festival to explore the link between HCMV. health and singing, with a particular We would love to hear from focus on inflammatory lung diseases. you about your achievements. The next application deadline is 1 September. Have you or a colleague recently You can find out more at www.immunology. The next application deadline is 1 July. received grant funding, passed org/grants-and-prizes/summer-placement- For more details, visit www.immunology. your PhD viva or accepted a new award-scheme. org/grants-and-prizes/communicating- appointment? If so, let us know by immunology. emailing [email protected].

Immunology News | June 2019 22 EDUCATION & CAREERS

accepting my current position over my offers from other companies. Whereas the primary focus of the company is to explore FUTURE the potential of gamma delta T cells in a clinical setting, the company also dedicates resources to understanding the biology behind gamma delta T cells, ensuring that FOCUS we are contributing to the wider scientific field too. It’s no surprise that the company Set your alarm – has hired from world-leading gamma delta and immunology labs, and there is no shortage of expertise at all levels of adjusting to life the company. Dr Paolo Paoletti, Dr Natalie Mount and Dr Michael Koslowski, our CEO, CSO and CMO respectively, have years of in industry experience in academia between them prior to moving into industry themselves, BSI member, Mihil Patel, finished his ensuring that that the company maintains PhD at Cardiff University last year its scientific rigour while driving hard and has since taken up the role of to develop potential therapies. Research Scientist at GammaDelta Mihil Patel Strict standards and Therapeutics. Here, he discusses how electronic lab books he found the transition from working Taking the plunge into industry One aspect that I really value is how in academia to industry and what he’s I was straight on to the job pages of the workload is often shared between learnt as a result. big pharma companies, LinkedIn and colleagues. As most of us can attest, recruitment agencies. It was clear from almost all experiments during a PhD Viva day. Ironic that three and a half years the get-go – now is a good time to be an are solo efforts, regardless of how small of toil would be condensed into as many immunologist. With immunotherapies and large. Here though, the work is very hours (3h 53min to be precise – my Chair being pushed hard by companies collaborative. If a large experiment is timed it and thought nothing of taking small and large, there were plenty of conceived, then the work is planned and candid pictures of me during the whole opportunities for someone straight executed by several scientists ensuring process). The success was followed with out of a PhD with a range of cellular it’s performed faster and more efficiently. the post-viva formalities – corrections, and molecular biology techniques. Unlike in academia, where a lab book entry dinners, smugness. Reality quickly To cut a long story short, the main can be minimalist, or non-existent, biotech crashed down on me, as I’d bled my reason for leaving academia was that I companies use electronic lab books in supervisors dry of temporary funding. I wanted to apply my skills learnt during which data is entered so that colleagues needed a job. It was time to put an end my PhD in viral immunology in a more across different sites can access it and to this extended state of adolescence. tangible way. After several Skype and face- reproduce the experiment as needed. to-face interviews, I accepted a position at This also allows traceability and time- ©Shutterstock/whanwhan.ai GammaDelta Therapeutics. I had a fairly stamped entries, which is important when good idea of what I was getting into: a considering the filing of patent applications. full-on cellular immunotherapy company. As our goal is to have a product in the Exactly what I wanted. The company is clinic, many of the reagents we use in still new, having only been spun out of our preclinical studies need to adhere to King’s College London and the Francis strict standards to meet the guidelines Crick Institute in 2016. As such, there’s a of regulatory bodies. This means keeping mix of an academic and company culture, strictly to use-by dates or sometimes and there’s still emphasis on keeping using GMP grade materials and reagents. up with the traditions of academia such It’s for the same reason that some as publishing papers, collaborations experiments are planned and executed to and attending conferences. This is answer specific questions (referred to as something that I was keen to understand data packages), rather than out of sheer at my interview as I was motivated to academic curiosity. I knew this would be join a company driven by science. the case before coming to industry, but That was a main deciding factor in for me this is a good thing as before it ‘Unlike in academia, where a lab book entry can be minimalist, or non-existent, biotech companies use electronic lab books in which data is entered so that colleagues across different sites can access it and reproduce the experiment as needed.’

Immunology News | June 2019 EDUCATION & CAREERS 23

was all too easy to let ideas snowball into huge experiments, which wouldn’t always ‘Gone is the overt informality. I’m in work due to workload management. Adapting to demands a professional environment; I don’t It’s true what you’ve most likely heard; in industry you need to be flexible. If certain walk around the office without shoes projects need more resources, then colleagues will be drafted in from other anymore or wear a bandana, and I even areas to help at short notice. However, as a stoic optimist, I see this as an opportunity set an alarm in the morning.’ to learn something new and build my skill set. Lastly as this is a company, with boards and shareholders, there’s a set are based around Oxford, Cambridge and anywhere else. Moving from academia to of business lingo which is always thrown London so if this is a decision you are industry is not something I regret. What around and roots itself into the office considering, then you need to consider I miss about academia is specific to my vernacular (‘offline’ meetings anyone?). setting your sights towards said ‘Golden experience and circumstances during my Of course, there are things that can’t Triangle’. This was tough for me as I’d PhD. As with academic labs, I suspect that easily be replaced by moving out of become an adopted son of Wales during all biotechs are different and have their academia. The flexibility of academia meant my PhD and was part of such a friendly own quirks and ways of working, though I I was free to do a lot of outreach work at lab, which I’m still in touch with. feel quite fortunate to have landed on my schools and festivals, which abruptly came feet here at GammaDelta Therapeutics. Science is science to an end. Gone is the overt informality. I’m in a professional environment; I don’t walk At the end of the day science is science. Mihil Patel around the office without shoes anymore or I still put the right controls into my Research Scientist wear a bandana, and I even set an alarm in experiment, I still attend weekly lab GammaDelta Therapeutics the morning. I’ve become more organised meetings and I still sing out loud when www.gammadeltatx.com since starting here which is necessary as no one else is in the lab. The learning the company currently operates across two curve at first was steep, but this would different sites in London. Most biotechs have been the case if I was to do postdoc ©Shutterstock/karnoff

Immunology News | June 2019 24 EDUCATION & CAREERS FUTURE Making BSI Congress FOCUS more accessible Ensuring that the BSI Congress is accessible to all is extremely KIT days to attend ECI to ‘keep in touch’ important to us. This year for our with the current immunology findings in Congress in Liverpool, on 2–5 Europe. So, I wrote my abstract soon after December, we are rolling out two my daughter’s birth, and was selected new initiatives to help those with to talk at the meeting in an ageing and carer needs to attend. Our aim is to immunity session. Additionally, after I had registered, I was also was asked to chair make this event accessible to as wide a session. an audience as possible. On the first day of the ECI, I chaired the session on mononuclear phagocyte Crèche development (predominantly in mice), We will have an onsite crèche at the not my area of expertise. I was a little BSI Congress 2019 in Liverpool to care nervous about this, but after discussing for delegates’ children aged 0–12. You how to split the chairing with the other will need to apply in advance to secure chairperson, I felt more at ease. Chairing a place for your child/ren. The BSI will the session meant that I listened subsidise the creche and childcare, more intently to talks, and actually I however subsidised fees will apply. really enjoyed it and learnt more than I expected. Carer grants The following day, the BSI held a For those who have caring responsibilities ‘meet-up’ in the evening at their stand at home, be this looking after children Attending an immunology for BSI members. I took Jamie along as or older members of the family, or those conference while on I thought it would be good to get her into that need carers themselves, the BSI is immunology early, and I had a great time launching a new grant scheme to help maternity leave speaking to other members and friends. cover the costs of bringing in extra support I think Jamie enjoyed her time at the while you attend the BSI Congress. BSI member Emma Chambers recently meeting too! The next day I had my talk in Grants of up to £300 will be available. attended the European Congress of the afternoon, which went well – and I got Immunology (ECI) while on maternity excellent feedback from the audience. I These initiatives are in addition to leave with her daughter Jamie. really liked the session as it covered a lot other provisions already in place to Here, she writes about the experience. of human work, and I found it interesting increase accessibility at Congress, hearing about the other speakers’ ageing such as breastfeeding facilities. More Last year, I had my daughter, Jamie, research. information on both the schemes and wanted to go to a conference while Overall, I found attending the ECI a listed above and how to apply will be on maternity leave to keep up with the rewarding experience and I would like available on the BSI website shortly. latest immunology studies. As ECI was to thank the BSI for my travel grant and in Amsterdam, and the journey was for facilitating my attendance. Having ©Shutterstock/Dave Clark Digital Photo doable with a young baby, I applied for time to listen to research and catch up a BSI travel grant to attend. Prior to my with friends and colleagues, I generally application, I had been successful in my found my attendance to be a rewarding application to my division’s maternity/ experience. I hope this article highlights paternity fund – to cover the costs of that there are ways to continue attending my daughter attending, as I was still conferences when you have a small family breastfeeding, and my husband’s costs – – and that the BSI is providing funding as he was kindly providing childcare while opportunities to facilitate attendance of I was at the meeting. Luckily, my BSI young parents at conferences. travel grant application to cover my costs was also successful. Emma Chambers While on maternity leave, you’re Postdoctoral researcher, allocated ‘keeping in touch’ (KIT) days to University College London use when you want to attend conferences or just to go into the lab to keep on top of your work. At UCL, you’re given KIT days back as annual leave when you return to work. I decided to use some

Immunology News | June 2019 BSI REGIONAL AND AFFINITY GROUPS 25 Making BSI Congress BSI Regional & Affinity more accessible Group update

It’s been a busy few months for our Groups with lots of conferences taking place. Here our Group reps take you on a whistle stop tour of some of their activities. BSI Immunometabolism Group Upon inception, our aim for the BSI Immunometabolism Affinity Group was to create a UK-based network of like-minded researchers. With this in mind, on the 14–15 experience following major injury. Using March 2019, we hosted our inaugural meeting, some arresting clinical case studies, he Attendees and speakers alike clearly ‘Fuelling the immune response’, in Newcastle. highlighted that understanding the early enjoyed the event, with speaker feedback We are pleased to report that the meeting immune events following traumatic injury including: was a success (if we say so ourselves!). is crucial to developing new interventions “I must thank you for inviting me to this It was very well attended (attracting 161 to enhance survival and recovery following great meeting! One of the best meetings delegates), made a huge ‘splash’ on our major trauma. Other speakers examined, I have attended in the last 5 years.” social media platform (@BSI_immunomet among topics such as, ultra-early immune “I very much enjoyed the meeting – it on Twitter), and featured a great line- response to trauma and neutrophil responses was a real privilege to attend. Really up of distinguished speakers, including during inflammation, infection, and sepsis. brilliant programme.” an inspiring tour de force on autophagy A key message that resonated throughout from our keynote speaker, Prof. Doug this meeting was the importance of Green. Feedback from our attendees was furthering our understanding of the early BSI Comparative exceptional, with an overwhelming majority immune response to traumatic injury and of participants agreeing that the talks were was summarised in the final slide from the & Veterinary excellent, that the balance of early and keynote speaker, which simply stated ‘Time Immunology Group more established researchers was ideal for trauma immunology’. and indicating that they would attend this Building on the success of our inaugural event again. A central point to highlight was meeting on B cells in November 2018, the the sheer abundance of unpublished data BSI Inflammation Group BSI’s Comparative & Veterinary Immunology presented at this meeting. This was truly Group (CVIG) organised a second meeting in the spirit of a collaborative atmosphere, The University of Edinburgh Centre for on ‘Non-conventional T cells in health and and served to pique the interest of our Inflammation Research and the BSI’s disease’. This topic is of great interest to audience. Our meeting also boasted plenty Inflammation Affinity Group co-hosted an veterinary immunologists because of the of networking opportunities, including a international conference, ‘Inflammation: wide variations in numbers of these cells in dancefloor which proved popular among from initiation to restoration’ over 24–26 commercially important animal species. some of our delegates! April 2019, in Edinburgh. This was a very stimulating and The 200 attendees enjoyed a superb informative meeting, which brought together selection of talks from a stellar cast of experts in large farm animals, chickens, BSI Infection & international and local speakers; examining mice and humans, providing an excellent Immunity Group the role of inflammation in causing tissue opportunity to compare non-conventional damage and the loss of tissue homeostasis, T cells across these species. The excellent In March 2019, the BSI’s Infection & through modulation of the immune system organisation, stunning setting overlooking Immunity Affinity Group held a one day by inflammatory processes, and into the Tower Bridge and the Thames, and good workshop on ‘Trauma immunology’ at the repair and regeneration of tissue and food and refreshments, all contributed to University of Birmingham, attended by resolution of inflammation. the lively discussion and success of the 60 delegates. Its aim was to highlight our These sessions were complemented by meeting. Feedback was that, “this was a developing understanding of the importance excellent short talks, a very well received great little meeting – there should be more of the immune response in progression and Early Careers Day, and a terrific evening like this”, with the conference receiving 4.7/5 outcome of traumatic injury. with the award-winning Science Ceilidh on the feedback survey. The meeting was Keynote speaker, Professor Karim Brohi group (including dancing the ‘Dashing White attended by 100 delegates. We are grateful (QMUL), a trauma surgeon, described the Blood Cell’), all enhanced by some beautiful to the BSI and the UK Veterinary Vaccinology distinct clinical trajectories that patients Edinburgh sunshine! Network (UK VVN) for their support.

Immunology News | June 2019 26 JOURNAL NEWS Immune Update The BSI A round-up of new research published in the British Society for Immunology’s official journalsImmunology and Clinical & Experimental Immunology. Members journals can access these journals free of charge at www.immunology.org/journals.

Immunology

Knowns and unknowns of tissue-resident memory T cells ©Shutterstock/Juan Gartner In this Editorial, Altmann considers the gaps macrophages and dendritic cells also in our understanding of tissue-resident show tissue-specific resident phenotypes. memory T cells (TRM). Non-circulating Transcriptomics has been able to explain T cells remain after a localised immune tissue residence, but larger questions still response. Why this subset of memory cells remain. Altmann suggests that longitudinal is different from the circulating population transcriptomic profiling may be able to is unclear. The differences between CD4 determine where TRMs come from and why and CD8 TRMs are also a mystery. While they remain. recent research has discovered a core transcriptomic signature for TRMs, there Altmann 2019 Immunology 157 1–2 is little variance between sites. Tregs, https://bit.ly/2LIpYZT

Tregs promote tissue repair via Th1 and Th17 responses in LPS-induced ARDS

Acute respiratory distress syndrome (ARDS) of Tregs with a PC61 anti-CD25 antibody impacted by reduced TGF-β expression. is associated with strong regulatory T cell interfered with inflammation resolution by The data show that Tregs are vital for (Treg) infiltration in the lung, but the role downregulating neutrophils, upregulating tissue repair and the resolution of LPS- of Th cells in bacterial-induced infectious macrophages and impairing lung epithelium induced pulmonary inflammation by their acute inflammation is ill-defined. Tanet and endothelial cell proliferation. The Th1 modulation of Th1 and Th17 responses. al. investigated the effect of Treg depletion and Th17 responses were also impaired. on Th activity in a mouse model of ARDS. Treg depletion may impair conversion Th Tan et al. 2019 Immunology 157 151–162 ARDS was induced in a mouse model cells, leading to a reduced pool of Th1 and https://bit.ly/2Yw3pt4 using lipopolysaccharide (LPS). Depletion Th17 cells. Th differentiation may also be Clinical & Experimental Immunology Sensing between reactions – how the metabolic microenvironment shapes immunity Perception of potential threat is key for how immune functionality during infections, survival. The immune system constantly cancer or autoimmunity, as exemplified by patrols the organism scanning for potential short-chain fatty acids, lactate and reactive pathogenic or malignant danger. Recent oxygen species, can be shaped by metabolic evidence suggests that immunosurveillance intermediates. not only relies on classic receptors, but is also based on sensing of the metabolic Lötscher & Balmer 2019 Clinical & environment. Metabolites interact in intermediates. This new perspective opens Experimental Immunology doi:10.1111/ numerous ways with immune cells and the door for potential, future therapeutic cei.13291 https://bit.ly/2V986HZ are therefore more than just reaction strategies. Lötscher & Balmer describe

EAntibody responses elicited in infants born to mothers vaccinated in pregnancy The maternal tetanus, diphtheria and of immunoglobulin (Ig)G against pertussis infants with higher transfer of DTx and TTx acellular pertussis (Tdap) vaccination toxin (PTx), filamentous haemagglutinin antibody in Tdap-vaccinated pregnancies programme in the UK has successfully (FHA), pertactin (Prn), diphtheria toxin compared with unvaccinated pregnancies. reduced cases of pertussis in young infants. (DTx), tetanus toxoid (TTx) Haemophilus The results support maternal immunisation It is important to investigate the persistence influenzae type b (Hib) and Streptococcus as a method of protecting vulnerable of maternal antibodies during infancy pneumoniae in mothers and infants at birth, infants during their first weeks of life. and the possible interference of maternal and in infants at 7 weeks and at 5 months. antibodies with infant responses to They found, among other results, that Rice et al. 2019 Clinical & Experimental vaccines. Rice et al. recruited mother–infant Tdap-vaccinated women had significantly Immunology doi:10.1111/cei.13275 pairs from vaccinated and unvaccinated higher antibody against Tdap antigens. All https://bit.ly/2JKqFj4 pregnancies and measured concentrations antibodies were actively transferred to the

Immunology News | June 2019 JOURNAL NEWS 27

A summary of some of the latest papers from the world of immunology. Around the Written by Lizzie Billington, Edd James, Louisa James, Donald Palmer journals and Mihil Patel. ©Shutterstock/Sergey Nivans Systemic clinical tumour regressions and potentiation of PD1 blockade with in situ vaccination Despite advances in treatment, indolent antigens (TLR3 agonist). This approach is non-Hodgkin’s lymphomas are incurable and shown to induce responses in preclinical do not respond well to checkpoint blockade. models and patients, although the trial Here, Hammerich and colleagues show that is ongoing. Inclusion of PD-1 blockade despite being able to directly prime T cells, dramatically increased the efficacy of the the ability to induce protective responses approach in the preclinical model. These requires cross-presentation of tumour findings highlight the importance of ensuring antigens. With this knowledge they developed tumour antigens are presented in an effective an in situ vaccine combining three aspects way to promote anti-T cell responses. to i) increase tumour immunogenicity (radiotherapy), ii) promote the recruitment Hammerich et al. 2019 Nature Medicine and differentiation of dendritic cells (Flt3L) doi: 10.1038/s41591-019-0410-x Regulatory effects of local and iii) promote the uptake of tumour microenvironment in the lung Different antibody responses in ducks vs chickens following Svedberg and colleagues have revealed a critical role for the airway influenza infection had a weaker antibody response than microenvironment in regulating immune Ducks are known to be more tolerant to chickens after intranasal infection, with cell activation. They show that alveolar avian influenza viruses (AIV) than chickens. lower titres and delayed seroconversion. macrophages, unlike macrophages Aquatic waterfowl are a reservoir that shed However, after intravenous infection, ducks from other sites, are hyporesponsive to but do not show clinical signs. However, had a more robust antibody response at IL-4 despite comparable levels of IL-4 the mechanism for duck tolerance of AIV 2–3 d.p.i. Ducks also showed limited viral receptor expression. Metabolic profiling is not fully understood. Yang et al. have dissemination compared with chickens, who demonstrated that alveolar macrophages identified the humoral immune response suffered systemic infection. These findings have a distinct metabolic state, with as possibly having a critical role in influenza indicate the humoral response could be impaired glycolysis and reduced respiratory resistance. They infected ducks and chickens important in AIV resistance in ducks. capacity that limits their ability to respond intranasally or intravenously with H9N2 AIV, to IL-4. The hyporesponsive phenotype then compared kinetics and magnitude of Yang et al. 2019 Virology Journal 16 was lost following in vitro culture, antibody responses. They found that ducks doi: 10.1186/s12985-019-1150-8 accompanied by increased glycolytic activity. This demonstrates that the airway Chronic inflammation permanently reshapes tissue-resident microenvironment regulates the activity of alveolar macrophages by modulating immunity in celiac disease their metabolic state. As well as Gamma delta T cells take centre stage in a expression in small intestine biopsies. While highlighting the important role of the local huge undertaking by Mayassi et al. which mucosal BTNL8 expression was recovered microenvironment in regulating immunity, furthers understanding of celiac disease in patients adhering to a gluten-free diet, this study raises the possibility that (CeD) and Vd1+ T cells. Innate-like NKR this did not restore the Vd1+ phenotype. This airway responsiveness could be modified expressing Vd1+ intraepithelial lymphocytes work indicates that the changes that occur therapeutically by targeting metabolic were lost in CeD, and did not recover in to the tissue-resident Vd1+ compartment pathways. patients avoiding gluten. Transcriptional are permanent and occur early on in CeD. analysis combined with TCR sequencing Svedberg et al. 2019 Nature Immunology 20 found that the intraepithelial lymphocyte Mayassi et al. 2019 Cell 571–580 doi: s41590-019-0352-y compartment was permanently reshaped in doi: 10.1016/j.cell.2018.12.039 CeD. Patients with CeD had reduced BTNL3/8

Longitudinal profiling of human blood transcriptome in healthy and lupus pregnancy It is now recognised that the generation establish foetal tolerance. To investigate pregnancy complications there is a failure of maternal immunological tolerance is this hypothesis, the authors performed to downregulate these transcriptional required for the successful survival of transcriptional profiling of whole-blood signatures together with the presence of any allogenic foetus. SLE is a systemic from healthy and SLE mothers at various activated CD4 T cells. These observations autoimmune disease associated with time points throughout their pregnancy. highlight the importance of establishing inflammation in joints and other organs. They observed downregulation of multiple foetal tolerance and the potential to Moreover, female patients with this immune signatures, including type 1 IFN use these immunological signatures as disorder have an increased risk of from healthy and non-complicated SLE biomarkers to determine healthy pregnancy. pregnancy complications such as pre- pregnancy, consistent with the idea that eclampsia and other adverse effects, pregnancy modulates the immune system. Hong et al. 2019 Journal of Experimental which seems to suggest a failure to However, in SLE patients that exhibited Medicine doi: 10.1084/jem.20190185

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