Dr Karel-Lodewijk Verleysen Prize

Professor Adrian Liston has been selected for the Prijs Dr. Karel-Lodewijk Verleysen for his work on the development of a safe and effective immune system. Professor Liston received his PhD from the Australian National University in Canberra, Australia, for seminal work on the role of the thymus in eliminating autoreactive T cells from the repoirtoire, a process known as immunological tolerance. His doctoral research identified defects in thymic tolerance as a key mechanism in the development of autoimmune disease.

Following his PhD in 2005, Professor Liston moved to the University of Washington in the United States of America in order to continue his research on T cell tolerance, performing some of the earliest experiments on the generation of regulatory T cells, a cell type that has come to dominate the field of autoimmunity in recent years.

Professor Liston was recruited to Belgium in 2009 by the VIB and University of Leuven, where he became a professor (hoofddocent) at the age of 28. In the last 6 years he has built up a laboratory of 15 researchers, dedicated to understanding the mechanisms of immune tolerance failure during autoimmunity and immunodeficiency.

Professor Liston has published more than 90 research papers, over a diverse set of topics in immunology and genetics and with publications in the top international journals such as Nature Immunology, Nature Medicine and Immunity. Of the many important findings, I would like to briefly highlight just four.

First, in collaboration with Cambridge University, Professor Liston identified a new cell type in 2011, the follicular regulatory T cell. This new cell type controls the strength of the antibody responses to vaccination, and is now thought to be important in diseases such as lupus.

Second, in 2012 Professor Liston’s research identified one of the key mechanisms that control the atrophy of the thymus with age. This reduction in the activity of the thymus is thought to be behind the poor vaccine responses of older persons. Professor Liston demonstrated that small non-coding RNA particles, known as microRNA, control the size of the thymus with age by altering the response to normal gut bacteria.

Third, Professor Liston has continued to work on the properties of regulatory T cells. In 2013 he published a seminal paper which systematically tested the signals that drive the life and death of regulatory T cells, identifying the key pathway that controls the quality of immune tolerance. This work is now being translated into immune therapeutics, where regulatory T cells are being seen as a high potential strategy to stop graft versus host disease.

Finally, Professor Liston is actively involved in the medical genetics of immune disorders. In the last few years Professor Liston has been working with clinicians at UZ Leuven to unravel the genetics behind patients with severe early-onset autoinflammation and immunodeficiency. This work has brought next generation sequencing into the diagnostic arena in immunology at UZ Leuven, and has identified several new immune disorders, such as the combined immunodeficiency and vasculopathy disorder caused by ADA2 mutation and several new genetic causes for immunodeficiency. Professor Liston is working hard to bring these advances in genetics into the standard diagnostic process, so that the genetic mechanism can inform on treatment options.

During his 6 years in Belgium, Professor Liston has received several major funding awards, including a Marie Curie Fellowship, a Juvenile Diabetes Research Foundation Career Development Award and a European Research Council Start Grant, bringing more than €3 million of international research funding into Belgium. He is a member of many national and international consortium and founded and directs the flow cytometry core facility in Leuven. Professor Liston is also active in science education and community outreach. For these contribution to medical research in Belgium, Professor Adrian Liston has been selected for the 2014 Prijs Dr. Karel-Lodewijk Verleysen.

Update on Wednesday, December 9, 2015 at 1:15PM by Adrian Liston

Dutch translation of the award citation:

Professor Adrian Liston werd voorgedragen voor de Prijs Dr. Karel-Lodewijk Verleysen voor zijn onderzoek naar de ontwikkeling van een gericht en effectief afweersysteem. Professor Liston voltooide zijn promotieonderzoek aan de Australian National University in Canberra, Australië. Hier verrichtte hij baanbrekend onderzoek naar de rol van de thymus bij het elimineren van zelf-reactieve T cellen uit het T cel repertoire – een proces dat bekend staat als immunologische tolerantie. Hij toonde aan dat bepaalde defecten in de tolerantiemechanismen in de thymus ten grondslag liggen aan de ontwikkeling van auto-immuunziekten.

Na het behalen van zijn doctoraat in 2005 zette Professor Liston zijn onderzoek naar T cel tolerantie voort aan The University of Washington in de USA. Hij onderzocht hier als een van de eerste wetenschappers de ontwikkeling van regulatoire T cellen, een type cel dat de laatste jaren het onderzoek naar auto-immuunziekten is gaan domineren.

Professor Liston werd in 2009 door het VIB en de Katholieke Universiteit van Leuven in dienst genomen als hoogleraar, op de zeer jonge leeftijd van 28 jaar. Gedurende de laatste 6 jaar heeft hij een laboratorium opgebouwd waarin hij leiding geeft aan 15 onderzoekers. Zijn laboratorium heeft als focus het ontrafelen van de mechanismen die aanleiding geven tot het falen van immunologische tolerantie bij auto-immuunziekten en immuundeficiënties.

Professor Liston heeft meer dan 90 wetenschappelijke artikelen gepubliceerd, waarin een breed scala aan immunologische en genetische onderwerpen aan de orde komt. Zijn publicaties zijn verschenen in invloedrijke internationale wetenschappelijke tijdschriften, zoals Nature Immunology, Nature Medicine and Immunity. Van zijn vele belangrijke ontdekkingen wil ik er vier kort uitlichten.

Als eerste heeft Professor Liston in 2011, in samenwerking met de Universiteit van Cambridge in het Verenigd Koninkrijk, een nieuw celtype ontdekt, genaamd de folliculaire regulatoire T cel. Dit celtype reguleert de mate van antilichaam respons na vaccinatie, en men vermoedt dat dit celtype een belangrijke rol speelt in auto-immuunziekten zoals lupus.

Als tweede heeft Professor Liston in 2012 één van de mechanismen geïdentificeerd die ten grondslag liggen aan het atrofiëren van de thymus tijdens veroudering. Het gebrek aan een goede vaccinatie respons bij ouderen kan te wijten zijn aan deze afname van thymusactiviteit. Professor Liston toonde aan dat de leeftijdsgebonden grootte van de thymus wordt gereguleerd door kleine stukjes niet-coderend RNA, of micro-RNA, doordat deze de respons tegen normale darmbacteriën aanpassen.

Als derde heeft Professor Liston zijn eerdere werk aan regulatoire T cellen voortgezet. In 2013 publiceerde hij een grensverleggend artikel waarin systematisch de signaalmoleculen werden bestudeerd welke beslissen over leven en dood in regulatoire T cellen. Tijdens dit onderzoek identificeerde hij het fundamentele mechanisme dat de mate van immunologische tolerantie bepaalt. Deze resultaten worden nu toegepast bij de ontwikkeling van therapieën voor graft versus host disease, waarbij het gebruik van regulatoire T cellen beschouwd worden als een veelbelovende nieuwe strategie.

Als laatste is Professor Liston actief betrokken bij het medisch-genetisch onderzoek van immuundeficiënties. Hij heeft de laatste jaren nauw samengewerkt met de clinici van het UZ Leuven om de genetische achtergrond van jonge patiënten met ernstige auto-immuun-ontstekingsziekten en immuundeficiënties te bepalen. Dit project heeft “Next Generation Sequencing” geïntroduceerd als nieuwe diagnostische test in het UZ Leuven. Verschillende nieuwe ziekten van het immuunsysteem zijn inmiddels ontdekt, zoals de gecombineerde immuundeficiëntie en vasculopathie die wordt veroorzaakt door een mutatie in het ADA2 gen. Ook voor andere immuundeficiënties zijn verscheidene nieuwe genetische oorzaken gevonden. Professor Liston zou graag zien dat deze nieuwe genetische technieken toegevoegd worden aan de gangbare diagnostiek, zodat het genetisch mechanisme achter deze ziekten wellicht aanwijzingen kan verstrekken voor verbeterde therapeutische opties.

Gedurende de 6 jaar die Professor Liston nu in België werkt is hij zeer succesvol geweest in het verkrijgen van onderzoeksfinanciering. Met de toekenning van een Marie Curie Fellowship, een Career Development Award van de Juvenile Diabetes Research Foundation, en een Start Grant van de European Research Council heeft hij meer dan 3 miljoen euro aan internationale onderzoeksfinanciering voor België verzekerd. Hij is lid van vele nationale en internationale consortia en heeft in Leuven een core faciliteit voor flowcytometrie opgericht, waarvan hij directeur is. Professor Liston is actief in het wetenschapsonderwijs en in wetenschapscommunicatie, met als doel een breed publiek bij het wetenschappelijk onderzoek te betrekken. Voor deze bijdragen aan het medisch onderzoek in België, is Professor Adrian Liston voorgedragen voor de 2014 Prijs Dr. Karel-Lodewijk Verleysen.

Scientists vs Cucumbers

There’s an awful cost to getting a PhD that no one talks about

It’s common knowledge that getting a PhD is hard. It’s meant to be. Some even say that if you’re not up all night working or skipping meals, you’re doing it wrong. But while PhD students are not so naive as to enter the program expecting an easy ride, there is a cost to the endeavor that no one talks about: a psychological one.

Worth a read.

Graduation of Dr Lei Tian

Congratulations to Dr Lei Tian, who graduated from her PhD in our lab!

(congratulations was a little late, but so was her thesis!)

Five worst things about being a scientist

Five best things about being a scientist

Academic careers: closed calls exclude women

Old continental European universities such as the University of Leuven have a major problem with diversity at the professor rank. In Leuven, for example, the professor ranks are overwhelmingly old, straight, white Flemish males, with their PhD from the University of Leuven (and often even the same department!). It is the very epitome of an old boys club, and there is absolutely no desire to change it. In my first months as a professor at Leuven I had multiple professors tell me to my face that, as a foreigner, I had no right to be here, since the positions were needed for Flemish graduates. And such overt insularity is not even the biggest problem - in a way I appreciated the honesty - it is the behind-the-scenes stuff which excludes or drives out anyone who does not look like they belong in the boys club. The problem doesn't stop at recruitment either - if you are a foreigner or a woman who slips through the cracks, there are plenty of ways of stopping you. Disproportionate amounts of clinical duties, low internal grant success, delayed promotions, the list goes on.

It should be fairly obvious that excluding 99.8% of the population is a poor start to any selection criteria seeking excellence, but the defenders of the old guard claim the opposite - that the very reason why we can't recruit more women is that the system is meritocratic, and if the best candidate is a man we need to take a man. It is an attractive argument, but it begs the question as to why the "best candidate" is almost always a man. I would argue that it is the closed recruitment process so often used in Leuven that ensures that top women do not apply, giving us a net decrease in excellence.

In this article, Dr Mathias Nielsen looked at the numbers in Denmark, broken down into "open" and closed recruitment calls. In "open" calls, 23% of successful candidates were women, while in closed calls created for a single candidate, only 12% of successful candidates were women. In other words, there is a substantial pathway for political appointments, and it is being used to favour men. This is a smoking gun for equality campaigners - proof that the appointment system is being exploited to stack the deck in favour of men. The one good thing that can be said for Aarhus University is that they provided information for the study, rather than trying to hide it.

I've been in committees at the University of Leuven discussing this question, and I've never seen anything more serious than the cliched "we need to do something about childcare" proposal (particuarly offensive in a system with one of the best childcare support networks in the world, as I can personally attest to). Since I'm use to arguing to a brick-wall on this topic, I might as well throw my proposals into the internet void. So here they are, my proposals for the University to increase quality and diversity:

1. Reduce the number of new professorships markedly. Having swarms of new professors just divides funding into such small units that everyone sinks. Plus we'll need the cash for a few of my other proposals below.
2. Create tenured senior scientist positions. Professors are not the only critical people to research, yet they are the only ones to get tenure. What I see happening a lot is that a senior professor has a fantastic senior scientist (who might not even want to be a professor) and they know that the only way they can keep them is to get them a professorship. The position is duly created, applied for and gained, and now the senior professor has a junior professor who in practice stays a senior scientist. These positions are important so let's formally create them, but be honest about it. Having this process will free up professorship positions for actual independent researchers.
3. Link every professorship to an attractive startup package. Better to have one professor who manages to take-off (and brings in money for the university) than three who crash and burn (and then sit on a 30 year work contract). The lack of a start-up package is the number one barrier to external recruits, as it means you essentially waste the first year unless you have a local sugar-daddy mentor, which only political recruits have.
4. Change the absurd language laws for science professors. The students learning science need to learn professional-level English, so why not teach them in English from day one? It certainly doesn't help them if they can write scientific papers in Flemish but not English, and you drive away most of the international talent if you formally require Dutch language skills you don't actually need for the job. Right now, the written English skills of our science graduates are not up to an international standard, simply because the students have not been forced to practice.
5. Back-end load the teaching duties. Over and over again I see universities load up junior professors with so much teaching that they can't succeed in research - and once the window of opportunity is closed it never opens up again. No teaching duties for the first five years, and progressively increasing teaching duties after that. Don't let the oldest free-load.
6. All positions need to be open calls. And don't even pretend that this is the case right now. A call that is only made in Dutch on the university website and only has a single applicant is not an open call. An open call has international advertising in English. It comes with a start-up package and does not have ultra-narrow terms of reference.
7. Audit the advertising of positions. If particular advertisers are only sending men your way, then drop them and use other ones that are better at reaching the full candidate pool.
8. At a minimum, interview four candidates of international quality. At least two of those candidates need to be women, and at least two should be foreign. If you can't find four candidates of international quality, then either your position is rubbish or your call wasn't open. At the end of the interviews if the Flemish man was the top candidate, then by all means hire him - the big problem seems to be that women aren't even interviewed in the first place. Give good women a chance to get a toe in and don't worry, they'll look after themselves. No woman or foreigner is expecting a hand-out, they just want the chance to compete on an open-playing field.
9. Audit clinical duties. If a professorship position comes with 50% clinical duties and 50% research duties, then the clinic should only be able to put you on for 50% of time. Pretty obvious, right? Yet over and over I see clinical professors being given clinical duties that are more than full-time, giving no time to grow a research position. And since young clinical professorships are the one place where women often suceed in high numbers, the clinical duties workload sabotages women's careers. A lot of the suggestions here cannot be applied to clinical positions (i.e., international recruitment is far more difficult when part of the job is patient care), so extra scrutiny needs to fall on clinical research positions to ensure they are being used appropriately.
10. International panels for grants and hiring. It completely gets around local politics, taking away the biggest tool in the old boy's club's arsenal.  Academics work for practically nothing, so it is a complete no-brainer, and standard in places such as Norway and Finland.
11. Audit the university. Let's pull back the curtain and take a look. There are dozens of different processes for hiring professors, which ones are hiring successful women and international recruits, and which don't. Shift funding to the tools that are successful, and stop those that are not. Compare the different department - which have recruited successful women, and what processes did they use? Force the under-performing departments to change their hiring policies.
12. Make all positions tenure-track, and actually get rid of people who don't make the cut. It is the one chance to get rid of sub-par professors and re-open the position up, let's actually use it.
13. Hold heads of department responsible. All new professors need to be able to show their productive independence (grants as promoter, publications as last author) within five years. If they haven't, then either the wrong person was hired or they were not supported enough - both are the responsibility of the head of department. If a head of department's toes were roasted every time a new professor ends up as a glorified post-doc, then the practice would shut down fairly quickly.
14. Listen to proposals that make you uncomfortable. The same old policies will give the same old results, so at least listen to some uncomfortable truths.

Erasmus scholars

The Erasmus program is a wonderful European project which drives brain-circulation around Europe. Our lab takes at least two Erasmus scholars every year, teaching them skills which will hopefully serve them well in their future career. In return we get skilled help in our projects, a network of future collaborators across Europe, and (last but not least) all of the advantages that come with intellectual diversity. Our last Erasmus scholar was Alper Çevirgel from Turkey, who drove forward the production of nanobodies in the lab and left us with a great protocol for Turkish coffee.

Once upon a time...

.... a scientist could write a concise grant and be funded

(translated: "Proposal: I need 10,000 Marks")

Being a mother and a scientist

Worth a read