Journals

The journals the lab publishes in:

Coauthors

An interesting idea from our head of Department - all of my coauthors in a word cloud:

In the news: Flanders Today

Q&A

Professor Adrian Liston

Professor Adrian Liston of life sciences research institute VIB headed the Belgian-Australian research team that discovered the genetics determining the strength of the immune system.

Which missing link in the immune system did you find? 
We focused on the regulatory T cells, which determine how our immune system reacts to possible health threats. In short, these T cells are in charge of the activity of white blood cells – the cells that defend us against viruses. When there are not enough regulatory T cells, our immune system can be overactive and cause allergies or autoimmune diseases such as diabetes and arthritis. In the opposite case, an underactive immune system allows infections and tumours to grow. We have now identified the genetic programme that sets the number of regulatory T cells, which should help us to keep the immune system ideally balanced.

Until now, you have worked with genetically modified mice 
Yes; the next step is to design and test drugs for humans. We are contacting academic research groups and pharmaceutical companies. Basic medicine can be developed in a time span of five years, but the clinical trials to perfect the working of the drugs can take another 10 years. In the near future, our findings will hopefully help, for example, to kill off the remaining cancer cells after chemotherapy. Later, we hope to develop the means to give an 80-year-old back an immune system that is as strong as that of a healthy teenager.

Was the Australian connection coincidental? 
No, I have Australian roots and finished my PhD at the Australian National University in Canberra. During my research there, I collaborated with experts, including the Walter and Eliza Hall Institute in Melbourne. Four Australian scientists from this institute took part in this recent research project. The team in Flanders consisted of seven researchers at the Autoimmune Genetics Laboratory of VIB and the University of Leuven. Our project lasted four years and was funded by the Flemish Agency for Innovation through Science and Technology and the European Research Council. The results were published in the scientific journal Nature Immunology.

Interview by Andy Furniere

(see original in Flanders Today)

Scientists discover molecular pathway that controls the strength of the immune system

Researchers led by Adrian Liston at VIB and the University of Leuven have discovered the genes that control the number of regulatory T cells in the body, a critical determinant for setting the strength of immune responses. This discovery may be an important starting point for the development of new drugs for the treatment of diseases of the immune system. The research has been published by the prestigious journal Nature Immunology.

In ideal circumstances the immune system is in balance, protecting us from infections and keeping us healthy. This balance can be disrupted, causing diseases of the immune system. An underactive immune system allows infections and tumours to grow, while an overactive immune system can drive allergies and autoimmune diseases such as diabetes and arthritis.

Regulatory T cells are a type of white blood cells that are specialised to keep the immune system in balance. To find out how the right level of balance is achieved, Adrian Liston, an expert in autoimmunity, teamed up with an Australian research group headed by Daniel Gray, an expert on cell death at Australia’s Walter and Eliza Hall Institute. In a 4 year research project funded by the IWT (agency for Innovation by Science and Technology) and the European Research Council, the two research groups found a network of genetic control that determined whether regulatory T cells lived or died, setting the level of immune activity in mice. The genes involved are almost unchanged between mice and humans, providing strong hope that the same pathway is active in patients.

“By working out the genetic control mechanism over regulatory T cell numbers we create a real challenge and opportunity for pharmaceutical researchers”, said Professor Liston. “We now have the blueprint for controlling the level of immune activation. The next step is to identify drugs which influence this system so that we can rectify disturbances when they occur. In theory, such drugs could be used to combat everything from cancer (when the immune system needs to be stimulated to clear cancer cells) to allergies and autoimmune diseases (when the immune system needs to be inhibited).”

(klik voor Nederlands)

Relevant scientific publication

The study is published in the leading journal Nature Immunology:

Update on Tuesday, July 16, 2013 at 11:13AM by Adrian Liston

Covered in ScienceDaily and SciCasts. Also now in Greek.

Autoimmune Genetics Laboratory in the news

De Standaard, 29-11-2012:

(English translation below)

De sfeer is hier collegialer' - Brain Gain

De Australiër Adrian Liston (32) werkt als hoofddocent immunologie voor de KU Leuven en als onderzoeker aan het VIB. ‘Ik had dubbel zoveel kunnen verdienen in de VS of Australië, maar dat is niet doorslaggevend.'

‘Wij zullen hier nog lang blijven, ja. België is een goede plek om aan onderzoek te doen en om onze zoon op te voeden.'

Bent u uiteindelijk tevreden met uw keuze voor België?

‘Het zou duidelijker moeten zijn dat je je werk in het Engels kunt doen. Publicaties, congressen, lessen,... het gebeurt allemaal in technisch Engels in onze branche.'

‘Ook de taal schrikt misschien af. Aan de KU Leuven moet je op papier in het Nederlands lesgeven, dat werkt drempelverhogend. In de praktijk kan je wel in het Engels lesgeven, zeker in de hogere graden. Maar dat weet een buitenlander niet.'

‘Academische vacatures mikken hier nog heel specifiek op de Belgische markt, ze worden vaak zelfs alleen intern uitgeschreven. Universiteiten zijn hier minder internationaal georiënteerd.'

‘Ik heb gestudeerd aan de Australian National University van Canberra en heb daarna een tijd gewerkt aan de University of Washington in Seattle', zegt Adrian Liston. Hij kreeg aanbiedingen uit Canada, Australië, Ierland, het Verenigd Koninkrijk en België.

Waarom is het België geworden?

‘Omdat het Vlaams Instituut voor Biotechnologie (VIB) zeer actief is in het rekruteren van internationale toponderzoekers. Ik was op zoek naar een plek waar ik onderzoek van het hoogste niveau kon doen. België leek me ook een aangenaam land, met een open houding tegenover mensen die Engels spreken. Ik vind hier ook een goed evenwicht tussen werk en vrije tijd.'

Ziet u verschillen in het academisch klimaat in België en pakweg de VS?

‘De sfeer is hier collegialer, omdat academisch onderzoek veel meer een kwestie van samenwerken is. Wie met buitenlandse onderzoeksgroepen samenwerkt, wordt daar financieel voor beloond. In de Verenigde Staten is het eerder belangrijk wat je als individu verwezenlijkt.'

‘Ik had ongeveer dubbel zoveel kunnen verdienen in de VS of in Australië. Het salaris van een senior researcher ligt best laag in België. Maar ik denk niet dat zoiets doorslaggevend is. De meeste academici willen vooral voldoende geld om aan research te doen. En op dat vlak doet België het tegenwoordig net heel goed.'

‘Er wordt ondanks de crisis niet drastisch gesnoeid in onderzoeksfondsen, in tegenstelling tot in Amerika. Als een academicus echt op zoek is naar een exuberant loon, zoekt hij het in de private sector.'

Wat kan een buitenlandse onderzoeker toch tegenhouden om hier te werken?

'Wij zullen hier nog lang blijven, ja. België is een goede plek om aan onderzoek te doen en om onze zoon op te voeden.'

 A rough English translation:

The atmosphere here is more collegial  - Brain Gain

The Australian Adrian Liston (32) works as a professor of immunology at the KU Leuven and a researcher at VIB. "I could earn twice as much in the U.S. or Australia, but that is not important."

"I studied at the Australian National University in Canberra and then worked at the University of Washington in Seattle," says Adrian Liston. He received offers from Canada, Australia, Ireland, the United Kingdom and Belgium.

Why come to Belgium?

"Because the VIB is very active in recruiting international researchers. I was looking for a place where I could do research at the highest level. Belgium seemed a pleasant country, with an open attitude towards people who speak English. Belgium also has a good work-life balance".

Do you see differences in the academic environment in Belgium and the U.S.?

"The atmosphere here is more collegial, which is important because academic research requires people to work together. Here the grant system rewards those who make international collaborations. In the United States the grants focus on individual researchers."

"I had the option to earn about twice as much in the U.S. or Australia. The salary of a senior researcher is relatively low in Belgium. But that was not a decisive issue. Most academics are more interested in knowing there is enough money to do the research they are interested in. And in this respect Belgium is doing well."

"There is no crisis in Belgium, unlike the drastic cuts in research funds in America. If an academic was focused on their personal salary they would move to the private sector."

What stops foreign researchers from coming here?

"Academic vacancies aim there focus very specifically on the Belgian market, they are often only internally issued. Universities are less internationally oriented."

"Also the language might scare off some people. At KU Leuven on paper you need to teach in Dutch. In practice you can teach in English, especially at the higher levels, but foreigners do not necessarily know this."

"It would attract a broader set of international researchers if they know they can work in English. Publications, conferences, seminars... it all happens in technical English in our profession."

Are you finally happy with your choice for Belgium?

"Yes, we will stay here for a long time. Belgium is a good place to do research and to raise our son."

This is more-or-less what I actually said. The one point that I think was left out is that Belgium shouldn't be concerned about the "brain drain". In science it is very important to have a "brain circulation", good ideas come from mixing people with different training and backgrounds, so it is actually a great thing for Belgian science if a lot of Belgians leave and non-Belgians come in. Rather than be concerned about the outflow, try to work more on the inflow, and then everyone wins.

Here is the article which started the issue (22% of Belgian researchers leave Belgian, only 18% of researchers came in from abroad, making a small net brain drain). And here is the opposing interview, from a Belgian researcher working in China.

Planning the paediatrics genetics screen

Only fair to have an age-appropriate represenative at the meeting...

Autoimmune Genetics Laboratory on the front cover of Cellular and Molecular Life Sciences

Our recent analysis of the function of microRNA-29 in the adaptive immune system was features on the front cover of the latest issue of Cellular and Molecular Life Sciences.

Adrian Liston, Aikaterini S Papadopoulou, Dina Danso-Abeam and James Dooley. ‘MicroRNA-29 in the adaptive immune system: setting the threshold’. 2012. Cellular and Molecular Life Sciences. 69(21) p3533. Pubmed | Direct access 

We also did some science

Lab retreat 2012 photos

Aire creates immune tolerance via an unconventional transcriptional mechanism

by Dina Danso-Abeam

The white blood cells of our immune system defend us from infection, a function which is coordinated by T cells. Immature T cells are formed with an ability to attack random targets (an adaptation to the rapid evolution of microbes), which means that by chance some targets are "self-targets" (normal proteins part of a healthy body). As a consequence, these "self-reactive" T cells can atatck the body, so it is critical to prevent them from causing autoimmune disease. To prevent autoimmunity, the immature T cells are screened in an organ called the thymus (located just above the heart), in order to ensure that all self-reactive T cells are eliminated.

The Aire gene plays an important part in eliminating self-raective T cells, by expressing genes that are normally restricted to specific organs (eg, insulin in the pancreas) in the thymus, providing full coverage for screening against self-reactivity. In patients that have mutations in the gene Aire, the thymus cannot provide full coverage of self-targets and fatal autoimmune disease develops. One of the mysteries of how Aire functions is its ability to express thousands of genes like insulin in the thymus. 

It has previously been shown that Aire is a transcription factor (meaning, it can bind DNA to activate genes and cause the expression of proteins) which can activate the expression of other transcription factors. We hypothesized that these secondary transcription factors might mediate the expression of the thousands of Aire-dependent genes like insulin; in effect, we predicted that Aire creates a cascade of transcription factors that results in the expression of thousands of genes.

In order to test this hypothesis, we investigated whether such a cascade regulates the transcription and tolerance of pancreas-specific antigens (e.g. insulin and glucagon) in the thymus. In the pancreas, Pdx1 is the key transcription factor which drives the expression of insulin. Interestingly both Pdx1 and insulin have been shown to be Aire-dependent in the thymus, so it was possible that Pdx1 was acting as a secondary transcription factor in the cascade by which Aire expresses insulin. Therefore we generated mice that specifically lack Pdx1 in the thymus.

By generating these mice, we found that expression of pancreatic-specific antigens such as insulin, needed Aire expression in the thymus, but did not need the transcription factor Pdx1. These results suggest that the broad tolerance that Aire creates in the thymus is not mediated by a conventional cascade of transcription factors, but rather relies on an unconventional transcriptional mechanism.  

This work will be published in a forthcoming issue of The European Journal of Immunology as:

Aire mediates thymic expression and tolerance of pancreatic antigens via an unconventional transcriptional mechanism

by Dina Danso-Abeam, Kim A Staats, Dean Franckaert, Ludo Van Den Bosch, Adrian Liston, Daniel H D Gray* and James Dooley*

AIG laboratory members successful at the FWO

This week we received exciting news that the Autoimmune Genetics laboratory had three successful candidates at the FWO, the premier fellowship program in Belgium. 

Dr Stephanie Humblet-Baron won an FWO Post-doctoral Fellowship award to research a new genetic disease caused by a loss of dendritic cells:

In the immune system, dendritic cells (DCs) are a subset of white blood cells that are specialized to activate lymphocytes when a pathogen is present In the absence of DCs, activation of lymphocytes and clearance of infections is impaired.  A new genetic disease has recently been identified where patients have no DCs, and surprisingly not only do they have poor clearance of infections, but they also have a large expansion of myeloid cells in their blood. For this project we have created a mouse model of this disease, which we will use to try to understand the biology of the myeloid expansion and to test potential therapeutics. 

Dr Susan Schlenner won a Pegasus Post-doctoral Fellowship award to move to the laboratory from Harvard. Here she will use novel genetic approaches to understand the biology of regulatory T cells.

Regulatory T cells are an important subset of white blood cells that have the ability to prevent the immune system from attacking components of the body (“autoimmunity”) and from attacking harmless environmental components (“allergy”). In order to exert this function the regulatory T cells need to be educated as to which components are safe and should be protected from immune attack. The location where this occurs is highly controversial as previously there have not been the correct tools to do functional tests. This project aims to generate a sophisticated set of genetically-altered mouse strains to allow measurement of where regulatory T cells are educated, and then to use these mice in models of autoimmunity and allergy. Having more knowledge about the education process of regulatory T cells may allow the future development of therapeutic interventions in those patients where regulatory T cells fail to prevent autoimmunity or allergy.

Dr Lien Van Eyck won an FWO PhD Fellowship, to move from the clinic to the laboratory to study auto-inflammatory diseases.

Blau Syndrome (BS) and Early Onset Sarcoidosis (EOS) are rare monogenic auto-inflammatory diseases characterized by a clinical triad of granulomatous arthritis, uveitis and rash. Extended manifestations with potentially high morbidity have been reported recently. The pathologic hallmark of BS/EOS is the presence of multinucleated giant cell and epithelioid cell granulomas in affected tissues. Both diseases are associated with gain-of-function mutations in the NOD2 gene. NOD2 is a specialised intracellular protein that plays a critical role in the regulation of the host innate immune response through recognising conserved microbial molecular signatures, thus leading to the induction of pro-inflammatory and anti-microbial responses as well as apoptosis. While the genetic basis of BS/EOS has been characterized, the molecular mechanisms by which NOD2 mutations drive granuloma formation and the development of sarcoidosis remain unclear. A better understanding of these mechanisms is of direct relevance for the development of targeted immunotherapies. The present project aims to determine the mechanisms by which NOD2 gain-of-function mutations lead to immunopathology in BS/EOS by developing a murine model with a gain-of-function mutation in NOD2. This model will allow for a full characterization of the immunopathology of NOD2 associated inflammation, and for the unravelling of molecular and cellular mechanisms involved in disease pathogenesis.