School of Biochemistry & Immunology Newsletter 2017/18

newsletter

SCHOOL OF

2017/18

Biochemistry & Immunology

WELCOME Greetings from the School of Biochemistry & Immunology. Coming towards the end of the 2017/2018 academic year, the School can reflect on another challenging but successful year in teaching and research. Our external examiners are universally positive regarding the high standard of the undergraduate students on our degree programmes, and improving the student experience for our undergraduate and postgraduate students is a priority.

The School is performing at a high level in terms of the quality of research published in leading academic journals, invited talks at International conferences and organisation of world-class symposia in Dublin.

It has been an outstanding year in terms of research funding with a number of new European Research Council, Science Foundation Ireland and Wellcome Trust grants being awarded to our PIs. There are also many productive collaborations in the School with industry, highlighting the relevance of our work to key national sectors and the direct contribution of Biochemistry and Immunology to the economy in terms of training excellent students, establishing start-ups and supporting mutually beneficial collaborations with the biotech and pharma sectors. The School has added to our many outstanding core facilities at Biomedical Sciences Institute enabling world-class research within the School and with our many collaborators across the College, the country and internationally.

Our staff are committed to outreach and increasingly engage with the public from school children to the general public through multiple approaches including open days, school visits, radio, and print and social media. We believe that we have many great stories to tell and want our voice to be heard.

All the best for the summer ahead.

Professor Ed Lavelle Head of School

Newsletter 2017 – 2018

How Malaria Tricks the Immune System is even more devious than previously thought.

The work, presented in the leading journal Nature Communications, reported that not only does the parasite hide from the body’s immune defences, it also employs an active strategy to deceive the immune system.

Within 12 hours of infecting red blood cells, the parasites send out DNA-filled nanovesicles that penetrate cells called monocytes. These cells are the immune system’s first line of defence against foreign invasion, sensing danger from afar and alerting other immune mechanisms to mount an effective response.

Professor Andrew Bowie Global efforts to eradicate malaria depend on our ability to outsmart the malaria parasite, but Plasmodium falciparum is notoriously clever. It is quick to develop resistance against medications and has such a complex life cycle that developing a vaccine against it has thus far proved elusive. More

than 200 million people contract malaria every year, and about 500,000 die. Most of the casualties are children under five.

Professor Andrew Bowie and his collaborators from The Weizmann Institute in Israel have shown recently that Plasmodium falciparum

Professor Bowie and his co-authors have identified an immune sensor in monocytes called STING which senses the malarial DNA and through which the parasite subverts the normal immune response to produce a response more favourable to the parasite.

Now that the subversive mechanism by which Plasmodium falciparum fools the immune response has been identified, it may be possible in the future to develop ways of blocking malarial infection.

Time of Day Affects Severity of Autoimmune Disease Circadian rhythms are generated by the body clock, allowing us to anticipate and respond to the 24-hour cycle of our planet. Maintaining a good body clock is generally believed to lead to good health for humans, and disrupting the circadian rhythm, for example by working night shifts, has been associated with immune diseases such as multiple sclerosis; however, the underlying molecular links have been unclear.

Professor Kingston Mills

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In the new study, Professor of Experimental Immunology Kingston Mills with Dr Caroline Sutton, and colleagues in Trinity and Dr Anne Curtis at RCSI show that immune responses and regulation of autoimmunity are affected by the time of the day at which the immune response is activated. Using mice as a model organism, they show that a master circadian gene, BMAL1, is responsible for sensing and acting on time-of-the-day cues to suppress

inflammation. Loss of BMAL1, or induction of autoimmunity at midday instead of midnight, causes more severe experimental autoimmune encephalomyelitis, which is an analogue of multiple sclerosis in mice.

Professor Mills said, ‘In the year that the Nobel Prize in Medicine was awarded for discoveries on the molecular mechanisms controlling the circadian rhythm, our exciting findings suggest that our immune system is programmed to respond better to infection and insults encountered at different times in the 24-hour clock.’

Although further investigations are needed to understand how to precisely modulate circadian rhythm or time-of-the-day cues for beneficial immunity, the findings in this article serve well to remind us the importance of ‘keeping the time’ when dealing with the immune system.

SCHOOL OF

Biochemistry & Immunology

Irish Research Council Awards

Dr Natalia Muñoz-Wolf (third from left) receives her award from the Irish Research Council

Dr Natalia Muñoz-Wolf was one of three Trinity researchers who were awarded medals of excellence by the Irish Research Council recently. The awards reflect the Council’s

support of exceptional researchers from early-career stage ensuring that Ireland has a vibrant research community. Dr Muñoz-Wolf, a post-doctoral research fellow in Dr Ed Lavelle’s

laboratory, was awarded the ‘Thomas Mitchell Medal of Excellence’ for being the top-ranked postdoctoral researcher in the science, technology, engineering and mathematics category. Dr Muñoz-Wolf’s research is in investigating determinants of morbidity and mortality in invasive pneumococcal disease (IPD). Building on previous work done in the Lavelle lab by Dr Clíona Ní Cheallaigh who uncovered the new Mal-IFN-γ receptor-signalling axis and its importance in tuberculosis, Dr Muñoz-Wolf is examining the role of Mal and the Mal-IFNγR axis in protection against IPD and investigating the molecular basis by which a single-nucleotide polymorphism (SNP), MalS180L, alters susceptibility to IPD. Dr Natalia Muñoz-Wolf has recently been awarded a new research grant by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) to expand her research and investigate the role of Mal and the Mal-S180L SNP in pneumococcal vaccine efficacy. Her project was jointly selected by ESCMID and the Federation of European Microbiological Societies (FEMS) as the 2018 winner of the ESCMID/ FEMS Research Fellowship, which recognises outstanding research in the field of infectious diseases by young researchers in Europe.

Potential Target for Attacking Disease-Causing Bacteria Antibiotic resistance is increasing globally, bringing with it the possibility that minor injuries and common infections could prove fatal. The development of new antibiotics is an urgent medical problem and the identification of microbial targets for new drugs is an important area of research.

Professor Martin Caffrey’s group have recently resolved the structural blueprint of a key enzyme from the disease-causing bacteria Pseudomonas aeruginosa and Escherichia coli. The enzyme, Lnt, is involved in the synthesis of lipoproteins, essential

components of the bacterial membrane. The elucidation of the structure of the enzyme is the first step in the development of a targeted drug against these bacteria but many problems remain unresolved. Firstly, similar enzymes are present in humans and other animals so any useful drug must be sufficiently specific to affect only the bacterial enzyme. Secondly, lipoproteins are potent activators of the immune system. The binding of a bacterial lipoprotein to a host receptor triggers an immune response in the host that tries to clear the infecting bacteria. A drug that binds to the target enzyme

Lnt could potentially also bind to the host receptor thereby inhibiting the necessary immune response. The structural blueprints generated by Professor Caffrey’s group provide a basis whereby differences between the bacterial enzyme, the mammalian enzyme and the immune response proteins might be exploited to produce a drug that only hits the bacterial target.

This important work was published in Nature Communications (DOI: 10.1038/ncomms15952).

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Newsletter 2017 – 2018

World’s First Nutrigenomic Supplement for Horses In a significant development for equine nutrigenomics, Professor Richard Porter, Dr Mary Rooney, both from Trinity Biomedical Sciences Institute, and Professor Emmeline Hill of UCD, have shown that the genetic makeup of a racehorse has a significant influence on the production of CoQ10 in horse muscle cells.

CoQ10, a key nutrient in the generation of energy in muscle mitochondria, is particularly important for sustained exercise. Increased levels of CoQ10 may result in more efficient energy production, delayed onset of fatigue during exercise, an improved response to exercise training and enhanced recovery following intense exercise.

Professor Hill is CSO of Plusvital, an equine science company that developed a test to identify genotypes in racehorses- the Speed Gene Test.

Using this genetic test, the research showed that thoroughbred horses that are T:T genetic types (suited to exercise requiring stamina), produced significantly lower cellular levels of CoQ10 than the other genetic types (C:C and C:T), but that these levels can be restored with supplementation.

In follow-up field trials, the scientists found that CoQ10 concentration in the muscle increased by 40% following nine weeks of

oral supplementation. The application of this research has resulted in the launch of the world’s first nutritional supplement based on published scientific research - EnerGeneQ10.

The research was published here:

Rooney MF, Porter RK, Katz LM, Hill EW (2017) Skeletal muscle mitochondrial bioenergetics and associations with myostatin genotypes in the Thoroughbred horse. PLoS ONE 12(11): e0186247.

SFI Early Career Researcher of the Year Science Foundation Ireland awarded the SFI Early Career Researcher to Dr Rachel McLoughlin in November 2017. The SFI awards recognise some of Ireland’s top researchers and acknowledge their dedication and determination to realise their research ambitions.

Dr Rachel McLoughlin is recognised internationally as a leading researcher in Staphylococcus aureus host pathogen interactions. Commenting on her delight at receiving the award Dr McLoughlin said, ‘I am extremely honoured to have been selected for this award and grateful to SFI for their continued support of my research programme. This is a wonderful endorsement of the impact that our work is making.’

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Dr Orlaigh Quinn, Secretary General, Department of Business, Enterprise and Innovation, Dr Rachel McLoughlin and Professor Mark Ferguson, Director General, Science Foundation Ireland

SCHOOL OF

Biochemistry & Immunology

Dr David Finlay Wins ERC Consolidator Award Dr David Finlay has won a prestigious European Research Commission (ERC) Consolidator Grant worth €2 million to investigate how nutrients can regulate the induction of T cell immune responses.

In recent years, scientists have demonstrated that cellular metabolism appears to be crucial in controlling immune responses; regulation of the response is acutely sensitive to nutrients that fuel important metabolic pathways and support nutrient-sensitive signalling pathways. Some of Dr David Finlay’s prior work has indicated - in vitro - that these process-driving nutrients are not equally available to all immune cells.

Dr Finlay hopes to demonstrate how local distributions of nutrients such as glucose, glutamine and leucine affect the immune response in vivo in mice.

Dr Finlay said, ‘We are developing new tools to allow us to study nutrient distribution at the single cell level in vivo, something that is not currently possible. If we can conclusively demonstrate that the availability of these nutrients is a key mechanism for controlling CD8 T cell immune responses, it would be a paradigm-shifting discovery that would open new horizons for the study of nutrient-regulated immune responses.’

SFI President of Ireland Future Research Leaders Award Adviser to the Government of Ireland, said, ’The President of Ireland Future Research Leaders Award is designed to attract to Ireland outstanding new and emerging research talent.

In supporting these talented and innovative individuals, we are delighted to recognise early career researchers who have already displayed exceptional leadership potential at the frontiers of knowledge. The development of leadership skills in these researchers early in their careers is vital to ensure research and innovation in Ireland continues to progress.’

Dr Tomás Ryan’s research focuses on the storage of memory in the brain and has potential implications on the identification and retrieval of lost memories in cases of amnesia.

President of Ireland, Michael D. Higgins, honoured the recipients of the SFI President of Ireland Future Research Leaders Award at Áras an Uachtaráin. Pictured left to right: Professor John Laffey, Dr Claire McCoy, Professor Mark Ferguson, Director General of Science Foundation Ireland and Chief Scientific Adviser to the Government of Ireland, President Michael D. Higgins, Dr Christina Kiel, Dr Tomás Ryan and Dr Lydia Lynch. Picture - Jason Clarke.

Two researchers in our School were recipients of the SFI President of Ireland Future Research Leaders Award. Dr Tomás Ryan, who was recruited from Massachusetts Institute of Technology, and Dr Lydia Lynch, recruited from Harvard University, were presented with

the awards by President Michael D. Higgins at a ceremony in Arás an Uachtaráin.

Congratulating the awardees, Professor Mark Ferguson, Director General of Science Foundation Ireland and Chief Scientific

Watch Dr Ryan talk about his work in a TEDMED talk here: www.youtube.com/watch?time_ continue=3&v=GT3ID4lxGhA Dr Lydia Lynch is researching novel therapeutics for obesity-related diseases. She will continue the research that was established in Harvard and will train the next generation of young scientists in the frontier field of immunometabolism.

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Newsletter 2017 – 2018

Trinity Innovation Awards 2017 Professor Luke O’Neill received the Provost Innovation Award 2017 for his outstanding contribution to innovation throughout his career. Professor O’Neill has published his research in some of the highest impact peer-reviewed journals such as Nature, Science, Cell and PNAS. He has consistently translated this academic success into patents, licences, industry collaborations and start-ups. This includes the formation of two campus companies, Inflamasome Ltd and Opsona Therapeutics Ltd, both focused on developing new drug therapies for the treatment of inflammatory diseases such as multiple sclerosis, Type 2 diabetes, Parkinson’s, Alzheimer’s, osteoarthritis and rheumatoid arthritis.

Congratulating him on the award, Provost, Dr Patrick Prendergast said, ‘I am delighted to be presenting this award tonight to Professor Luke O’Neill. Through his innovative research and

Provost Dr Patrick Prendergast and Professor Luke O’Neill

the commercialisation around it, he is making a real difference in society, by developing new drug therapies and improving the lives of people with inflammatory diseases. Trinity

academics have consistently achieved excellence in discovery and innovation, and Luke is one of our great exemplars in that field.’

Researchers Meet the Public TBSI, visitors could attend different workshops to find out more about vaccinations and immunology. This was followed by a public debate on whether vaccinations should be made mandatory. The panel included Professor Kingston Mills, Clíona Ní Cheallaigh, Aoife McLysaght and ethicist Louise Campbell (pictured). A lively debate ensued.

In September some of our researchers took part in PROBE (European Researchers’ Night), a night where visitors can meet researchers and

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learn about their work. The main event was in front square, where Stephanie Longet had a stall representing the team. At the JAB LAB event in

The Health Research Board facilitated the HRB RED ALERT: VACCINES event in December in the Science Gallery Dublin, where it was Dr Ed Lavelle’s turn to be on the panel. The evening consisted of a two-part series, where, after the debate, the audience was split into groups where they could ask questions more openly. Stephanie Longet and Aoife Gorman, both from Dr Ed Lavelle’s lab, helped to facilitate these groups. You can watch a video from the event here: www.youtube.com/watch?v=u_av2j09bHg

SCHOOL OF

Biochemistry & Immunology

League of European Research Universities (LERU) Doctoral Summer School Shauna Quinn, a PhD candidate in Professor Kingston Mills’ laboratory was part of the winning team in a citizen science competition run during the League of European Research Universities (LERU) Doctoral Summer School that took place in the University of Zurich in summer 2017.

The winning project ‘Letswakeapp’ – will poll citizen scientists to identify the best alarm tone for a good wake-up experience. The theme of its 2017 summer school, ‘Citizen Science – Nexus between Research and Public Engagement’, provided doctoral candidates with professional and personal development opportunities that may not be part of traditional PhD study.

Shauna Quinn (second row, third from the right) with some of the doctoral students attending the LERU summer school 2017

The project highlighted the importance of interdisciplinary collaboration to tackle major challenges in today’s global society.

Schrödinger at 75: The Future of Biology A group of the School’s academics including Professor Luke O’Neill, Professor Cliona O’Farrelly, Dr Tomás Ryan and Professor Mike Murphy, an alumus of our School, based in Cambridge, are organising a unique international meeting ‘Schrödinger at 75: The Future of Biology’ on 5-6 September 2018 at the National Concert Hall.

Tickets are €100. For more information and to book a ticket please visit www.tcd.ie/biosciences/whatislife/

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Interview with Alumna - Kate Fitzgerald 3. What appeals to you most about your current role? What are you working on?

Kate Fitzgerald, Professor of Medicine,Worcester Foundation Chair in Biomedical Sciences Director, Program in Innate Immunity Umass Medical School

1. What was your childhood ambition?

I am pretty sure I wanted to be a teacher. I remember having a blackboard on an easel and I have many memories of ‘teaching’ my younger siblings and neighbours in the front garden. I had a pointer and we had a mini classroom set up, it was the real thing. My parents said I was very serious about it all.

I love the scientific environment at Umass Medical School where I am now Professor of Medicine and Director of the Program in Innate Immunity. Umass is a special place to be a scientist. It’s incredibly collaborative and collegial (which is not a given at US institutions) and is filled with scientists at the cutting edge of diverse fields. Everyone there is invested in each other’s success and I think that is the key to what I like the most. In my lab we are working on trying to understand how the immune system distinguishes friend from foe. Early on our work was focused on defining key receptors on immune cells that recognise microbial components and how recognition of microbes leads to gene expression and protective immune responses. In the last few years we have turned our attention to understanding how the dysregulation of innate immunity underlies the pathogenesis of inflammatory diseases. In particular a major focus is on nucleic acid sensing pathways and how these pathways are involved in diseases such as Lupus. There are now targets that could lead to new drugs for these diseases so that’s exciting.

project was going nowhere. Somehow, he would find the one nugget of positive data and I would come out of those meetings motivated and driven to develop that aspect.

It’s an incredible strength of his and taught me to really persevere. Secondly, I didn’t appreciate it at the time but now looking back I also realise how supportive Luke was and is today of women in science. I have been fortunate to have had great mentors over the years and this aspect of being in his lab was very important for my career success. Mentors who support women early on in their careers are key to ensure that women move up through the ranks of academia. Lastly, the people in the O’Neill lab were fantastic in every way and remain great friends and collaborators to this day.

5. Have you any advice for students or fellow alumni?

I have very fond memories of my time at Trinity. Firstly, Luke O’Neill was a fantastic mentor. He was always enthusiastic about science. I would have a meeting with him weekly to go over progress, plan experiments etc. I remember going to those meetings at times feeling like my

I always encourage students to pursue a career in academic science or other aspects of science. I really love what I do. The freedom to explore and develop your own ideas and build your own group is very rewarding. I love interacting with students and seeing them develop and mature scientifically. That’s more rewarding than the papers in many ways. Finding great mentors along the way is the key to success. I think this is especially true for young women in science who want to have rewarding careers but balance the demands of a family life. It’s in many ways an ideal career to do this due to the flexibility. There are times when you are juggling all the balls in the air at once and they come crashing down. But it’s a lot of fun along the way.

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2. What made you decide to study biochemistry in Trinity?

I had just completed my BSc in Biochemistry at UCC and was looking for a PhD lab that was focused on signal transduction. I looked at several labs in the UK and my last interview was with Luke O’Neill at Trinity in the Biochemistry Department. Once I met Luke I was sold and knew that was the place to be. He was so enthusiastic and excited about science. It was infectious.

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