Our immune systems are incredibly diverse. How much of that diversity is due to our genes?

Each of our immune systems acts a little bit differently. Environmental factors have an impact, but so do our genes. A team of researchers in Leuven went looking for links between more than 10 million genetic variations and more than 50 immunological traits. Their findings help to explain why some people have a higher risk for immune diseases than others.

Our immune systems are molded by our unique genetic make-up. Add to that a complex mix of environmental drivers, and you get an enormous functional diversity. From an evolutionary point of view, this diversity is essential to minimize the chance that a pathogen could wipe out an entire population.

But the flip-side is that we’re also greatly diverse when it comes to susceptibility or resistance to a broad range of diseases – not only those with an obvious immunological component, such as autoimmunity, allergy, inflammation and cancer, but also those with a more indirect link to immune-deregulation, such as cardiovascular, metabolic and neurological diseases.

A genome-wide survey

While scientists have studied the links between genetic variations and a whole range of different diseases, the characterization of this “genotype-phenotype relationship” for the immune system itself has received far less attention.

That is why a team of scientists led by An Goris (KU Leuven) and Adrian Liston (VIB-KU Leuven) undertook a large genetic study with almost 500 participants. In a so-called genome-wide association study, or GWAS, they probed more than 10 million genetic variations, spread out across the genome, for links to 54 different traits relevant to adaptive immunity. This allowed the researchers to determine which genetic variants were, for example, typical for people with high or low levels of different pro- or anti-inflammatory cytokines.

“We found eight previously unknown associations,” says An Goris, lead geneticist of the study. “The strongest connection was for a genetic variant present in only 2% of the study participants.” All of the identified genetic associations provide important biological insights into what drives variation in our immune systems.

This is only the tip of the iceberg, according to Goris: “What we know now, explains about 10% of the variation, but we are still in the initial discovery phase. There might be many more genetic variants—including relatively rare ones—that affect our immune response and thus our susceptibility to certain diseases.”

Helping to map disease risk and refine treatment

Mapping how genetic variants affect immune function will not only help us understand disease mechanism better, it should also help to refine treatment options.

“The clearest example is the clinical implication offered by genetic variation in the RICTOR gene,” explains Adrian Liston, lead immunologist on the study. “We now know that RICTOR changes the production of a cytokine called IL-4, providing a new therapeutic target for treatment of autoimmune diseases and asthma.”

In many cases, the effects are more subtle and indirect, adds Liston: “Most people will carry dozens of genetic variants that may skew the immune system in a particular direction. This accounts for part of the reason why different people have different risks for immune diseases, but we are much more than the sum of our genes.”

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Lagou et al. 2018 Cell Reports. 'Genetic architecture of adaptive immune system identifies key immune regulators'.

New position at the Babraham Institute

I am pleased to annouce that in 2019 I will be taking up a new position as Senior Group Leader at the Babraham Institute in Cambridge. I have been at the VIB and University of Leuven for nearly 10 years, and it is time for a new chapter.

In 2009, me and James Dooley set up the Translational Immunology laboratory in Leuven. We walked into an empty room. No chair, no tables, no staff, no equiptment. I was 28 years old, barely out of a post-doc and completely unprepared for what was to come. Over the next 10 years we turned the laboratory into a thriving hub for immunology research in Leuven. We now run three research teams, headed by James Dooley, Susan Schlenner and Stephanie Humblet-Baron, and we set up and run two Core Facilities, for flow cytometry and genome engineering. My lab currently hosts 25 researchers and has trained another 100 immunologists over the years, who now have positions across Belgium and the world. We have brought more than €10 million into the university in research grants, including the prestigious ERC Start and ERC Consolidator awards. We have published more than 120 research papers over the past 10 years, including major studies in Nature Immunology, Nature Medicine, Nature Genetics and Science Translational Immunology. We have worked closely with the clinic here in Leuven, discovery new diseases and creating new therapeutic strategies for children with rare immune diseases. 

These successes are due to the work of the amazing scientists in the lab, in particular James, Susan, Stephanie and Pier-Andree. But we could not have had this success without institutional support. The VIB recruited me with the incredibly successful independent researcher program, which provided a high level of core funding and complete intellectual independence. The VIB also provided an environment rich in new technologies and a highly international culture of excellence. In particular I want to thank Jo Bury for starting the independent researcher program, and Bart De Strooper and Patrik Verstreken for creating a VIB department where the values of intellectual independence thrive. 

Patrik Verstreken, Director of VIB Center for Brain & Disease: "Adrian’s work has been nothing short of stellar, but what I appreciated the most is that he pushed us to think outside the box, that he brought amazing new technology to KU Leuven and VIB and that he drove the development of both the FACS core and Mutamouse.  Adrian has also always been a fierce advocate of equal opportunities for all, and for a more equal gender balance in research; I am sure he’ll continue this in the future.  Adiran is a role model for everybody in our center and he shows how hard work, inspiration and clever use of the many possibilities in our environment can propel you to the next stage in your career." 

We were jointly hosted by the University of Leuven. Here we were incredibly lucky to enter the university in an era where university management was actively seeking to remake this ancient institution into a modern, international hub of research excellence. In particular, Peter Marynen and Wim Robberecht in Biomedical Sciences, and Marc Van Ranst, in the department of immunology, never failed to turn a crisis into an opportunity. Each of these leaders was able to see both the barriers that faced foreign group leaders and also the opportunities that they presented, and under their tenure the university and department made enormous progress. Without their support I would never have been able to build up two core facilities, opening up new research tools to the entire community. I sincerely hope that the next generation of leadership continues this outwards facing ethos. 

Marc Van Ranst, Director of the KUL Department of Microbiology and Immunology: "Adrian is a top immunologist and a very appreciated member of our department and our departmental board. He is a smart innovator and scientific leader, and an all-round good guy. He is the driving force behind several core facilities such as Mutamouse and the FACS core. He will join the prestigious Babraham Institute at Cambridge where he will be a Group Leader in their Lymphocyte Signalling & Development cluster. Adrian will be the KU Leuven ambassador in Cambridge, and will remain involved in the activities of the Laboratory of Adaptive Immunity here in Leuven, exchanging students between Cambridge and our department. We wish him all possible success in this new phase in his career!"

The Translational Immunology laboratory in Leuven will not be closing down. Susan Schlenner is going to replace me as head of the laboratory, which will be renamed the Laboratory of Adaptive Immunity, and the laboratory will keep up two research teams (molecular Tregs, under Susan Schlenner, and clinical immunology, under Stephanie Humblet-Baron) and will continue to run both the FACS Core and MutaMouse. The tissue and disease team led by James Dooley will move with me to Cambridge, where our new adventure begins. This time, however, rather than landing in an empty room we will be embedded into the outstanding research environment of the Babraham Institute! A small team is coming with us, Oliver Burton and Carly Whyte, but new recruits are needed!

Babraham Institute welcomes three new research groups to study the ageing immune system

• Babraham Institute recruits three new immunologists as Group Leaders in the Lymphocyte Signalling & Development programme
• Drs Adrian Liston, Sarah Ross and Claudia Ribeiro de Almeida will be moving from VIB, Leuven, Belgium, the University of Dundee and the University of Oxford respectively.
• They bring new expertise in the regulation of the immune system by specialised regulatory T cells, the signals involved in T cell specialisation and understanding how B cells produce certain antibodies in response to illness.

Today the Babraham Institute in Cambridge, UK is pleased to announce the recruiting of three new principal investigators to their organisation. Dr Adrian Liston, an established lead researcher currently based at VIB and the University of Leuven (KU Leuven), Belgium, joins as a Senior Group Leader. Meanwhile Dr Sarah Ross from the University of Dundee and Dr Claudia Ribeiro de Almeida from the University of Oxford will both be relocating to start their own independent research groups as Tenure-Track Group Leaders. All three groups will join the Institute’s Lymphocyte Signalling & Development research programme.

Institute Director, Professor Michael Wakelam, said: “We are thrilled to have all three of these outstanding researchers bringing their skills and expertise to the Institute. It is crucial that we continue to build our expertise in new areas and work together to make new breakthroughs. These new groups will all be critical to achieving our goal of understanding the ageing immune system and realising our vision of healthier ageing and better long-health for everyone.

“We are particularly pleased to welcome Dr Liston who has been a long-time collaborator with the Institute and whose move from VIB reflects the importance of international exchange in research and the success of our participation in the EU-LIFE consortium of European research institutes in promoting shared opportunities, practices and values.”

Dr Liston’s group at VIB focuses on translational immunology. His work has included studies of regulatory T cells (Tregs) – cells that help to restrict the responses of the immune system. Tregs play an important role in avoiding autoimmune diseases and allergies where the immune system responds to the wrong things. His group have helped to identify a new type of Treg and provided the first clear idea of how Tregs are controlled. Major recent publications have focused on the role of the immune system in diabetes and the effect of age on the immune system. Dr Liston has collaborated often with the Linterman group and his work is expected to be an excellent complement for the Institute’s existing expertise.

Speaking about his new role Dr Liston said: “I was attracted to the Babraham Institute due to its international reputation for biological research. It is one of the few centres with such a strong history of converting strategic basic research into societal gain, with a culture of both diversity and intellectual freedom. I see the move to Babraham as a chance to invest in blue sky research with the long-term potential to transform immunology for the future.”

Dr Ross is currently a Postdoctoral Researcher with Professor Doreen Cantrell. She brings expertise in the analysis of signal transduction in T cells – understanding how molecules on and in these cells regulate their behaviour, particularly migration and differentiation. Her most recent published work focuses on the role of the signal molecule interleukin-2 in cell growth, division and specialisation of T cells.

Dr Ross said: “I am thrilled to be joining the Babraham Institute. My research links several existing research areas within the Institute, and the outstanding facilities and exciting opportunities to form collaborations makes it the perfect environment to launch my new lab. Together, I believe this will allow us to achieve a better understanding of both heathy and diseased immune responses.”

Dr Ribeiro de Almeida is presently working with Professor Nicholas Proudfoot as a Postdoctoral Researcher in Oxford. Her recent research has examined proteins called helicases in B cells of the immune system. She is interested in how these DNA- and RNA-unwinding proteins help B cells to respond to threats by producing different types of antibodies to combat infections. Earlier this year, she published work showing the importance of a helicase called DDX1 in the expression of IgH antibody genes.

Dr Ribeiro de Almeida said: “I am delighted to have the opportunity to start my own research group at the Babraham Institute. Throughout my career I have always felt very close to the Institute’s research and ethos. Being able to take the next step in my career in such a supportive and collaborative environment is very exciting.”

Head of the Institute’s Lymphocyte Signalling & Development programme, Dr Martin Turner said: “I am very pleased to have three outstanding new research groups joining our team. They bring critical expertise that are vital to achieving the programmes core BBSRC-funded goals. With the help of Drs Liston, Ross and Ribeiro de Almeida we can further enhance our understanding of signalling and control of the immune system, the response to infections and the effects of ageing on the immune system. I look forward to working alongside them all as they build their new groups here at the Institute."

Dr Ross will take up her new position at the Institute from 1^st October, while Dr Ribeiro de Almeida will join a month later on 1^st November. Dr Liston’s lab at the Institute will start work in early 2019.

About Dr Adrian Liston

Adrian Liston is a Belgian/Australian researcher. He gained his PhD with Professor Chris Goodnow at the Australian National University studying T cell tolerance and diabetes. He moved on to study regulatory T cells with Professor Sasha Rudensky at the University of Washington before starting his own lab at VIB in 2009. His independent laboratory has focused on translational immunology, using mouse models to help human health. Dr Liston has produced over 130 publications with over 5000 citations and has been awarded two ERC grants, the Eppendorf Prize and a Francqui Chair, among other honours. He also holds degrees in Public Health and Higher Education.

About Dr Sarah Ross

Sarah Ross comes from Scotland. She gained her PhD with Professor Sir Peter Downes in Dundee, investigating how oxygen-derived signalling molecules regulate cell functions. She obtained a FEBS long-term fellowship to move to UMC Utrecht, Netherlands in 2008 to research signalling pathways involved in the integrity of tissue architecture with Professor Johannes Bos before returning to Dundee to join Professor Cantrell in early 2013. She has 11 publications with over 300 citations. Sarah is interested in making science accessible through public engagement and supporting the development of young scientists.

About Dr Claudia Ribeiro de Almeida

Claudia Ribeiro de Almeida originates from Portugal. She studied Molecular Biology & Genetics at the University of Lisbon before moving to Erasmus MC, Rotterdam to gain a PhD with Dr Rudi Hendriks examining the role of the gene regulating protein CTCF in the development of lymphocyte immune cells. As a Postdoctoral Researcher, she initially moved to MRC-Clinical Sciences Centre (now MRC-LIMS) before joining the Proudfoot lab as an EMBO fellow.

About the Babraham Institute
The Babraham Institute undertakes world-class life sciences research to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. Our research focuses on cellular signalling, gene regulation and the impact of epigenetic regulation at different stages of life. By determining how the body reacts to dietary and environmental stimuli and manages microbial and viral interactions, we aim to improve wellbeing and support healthier ageing. The Institute receives core funding from the Biotechnology and Biological Sciences Research Council (BBSRC) through an Institute Core Capability Grant. 

About the BBSRC

The Biotechnology and Biological Sciences Research Council (BBSRC) is part of UK Research and Innovation, a non-departmental public body funded by a grant-in-aid from the UK government.

BBSRC invests in world-class bioscience research and training on behalf of the UK public. Our aim is to further scientific knowledge, to promote economic growth, wealth and job creation and to improve quality of life in the UK and beyond.

Funded by government, BBSRC invested £469 million in world-class bioscience in 2016-17. We support research and training in universities and strategically funded institutes. BBSRC research and the people we fund are helping society to meet major challenges, including food security, green energy and healthier, longer lives. Our investments underpin important UK economic sectors, such as farming, food, industrial biotechnology and pharmaceuticals.

Congratulations to Dr Vasiliki Lagou!

Congratulations to Dr Lagou, who successfully renewed her prestigious FWO Post-doctoral Fellowship award. Vasiliki will work on the genetic control of immune disorders in patients. 

Congratulations Dr Aleksandra Brajic!

 Congratulations to Dr Brajic, who was successful in the prestigious (and highly competitive) FWO Post-doctoral Fellowship awards. Aleksandra will work on developing new tools to study the function of regulatory T cells in kidney disease.

Seminar notes

Amazing lecture notes on my recent CIMR seminar from Dr Jane Goodall. You can follow her and her lecture notes on twitter @Beautifullight1

A new era for the Golden Pipette

Another lab retreat, and the Golden Pipette has found a new home. Dr Emanuela Pasciuto passed the batton on to Dr Carlos Roca, for the development of a revolutionary new software package for automated analysis of flow cytometry data. A first for the Golden Pipette, won for bioinformatics, and a first for Dr Roca, having never held a pipette before.

Translational Immunology: A Great Team!

Congratulations to Dr Aleksandra Brajic!

Dr Aleksandra Brajic just won the best poster award at the Center for Brain and Disease Research. Winning against such strong competition, and on a project that does not involve the brain, is a real achievement! Dr Brajic's work on the lncRNA Flatr and regulatory T cells will be published soon.

 

Translational Immunology lab in the news

Our research was featured tonight on VRT News:

Speaking roles by Carine Wouters, Erika Van Nieuwenhove and Adrian Liston. Cameos from Stephanie Humblet-Baron, John Barber and Pier-Andree Penttila

 

 

Original research: Van Nieuwenhove et al. 2018 Journal of Allergy and Clinical Immunology. "A kindred with mutant IKAROS and autoimmunity"

If you would like to support our clinical research, and allow us to take on more cases like these, you can make a tax-deductable donation the Ped IMID fund, by transferring to IBAN-number BE45 7340 1941 7789, BIC-code: KREDBEBB with the label "voor EBD-FOPIIA-O2010".