Treg plasticity

This is a great video by PhD candidate Steffie Junius, sharing what her PhD is on:

How do microbial biofilms evade the immune system?

Microbial biofilms are a major medical problem. While the immune system is excellent at picking off individual yeast or bacteria, when these pathgoens band together into a multicellular biofilm they gain the ability to evade the immune system. In a study just out in Frontiers of Immunology, we come up with a theoretical framework to understand how this immune evasion occurs. There are three basic models by which the biofilm could evade the immune system: 1) it could be immunologically silent, using the biofilm as a barrier to make sure that no microbial products leak out to alert the immune system; 2) it could trick the immune system, creating new products that get the immune system to attack in the wrong way; or 3) it could resist the immune system, using the biofilm to block the attack by host cells. By using a mouse model of Candida biofilm infection we were able to demonstrate that the third model is correct - the biofilm is neither silent or diverting, permitting the generation of an effective anti-Candida immune response. Instead, the biofilm acts to somehow block the immune attack on any cells that stay within the biofilm. These findings will allow researchers to focus on understanding the molecular mechanism of biofilm immune resistance, hopefully one day contributing to new treatments for biofilm infections.

Original study: A Framework for Understanding the Evasion of Host Immunity by Candida Biofilms. Garcia-Perez et al. 2018. Front. Immunol., https://doi.org/10.3389/fimmu.2018.00538

Interview with eLife on being a scientist parent

eLife in their Scientist and Parent series

At what career stage did you become a parent?

My partner and I did PhDs in Canberra, Australia, before post-doc’ing in Seattle, USA. After our post-docs my partner decided to move to industry while I wanted to take a shot on being an academic. At this point we relocated to Belgium and started a family. We were 30 years old at the time, in a new country and both starting out on new career pathways. Now our son is six years old, and all three of us have hit our stride, with happy lives at home and successful careers at work (well, for my wife and I, our son is not yet an astronaut).

What support have you received as a parent from your country (including parental leave), institution, and friends and family?

We moved to Belgium just before having a child, which means we were not able to draw upon our network of friends and family. My host institution did not provide any support, but Belgium in general has a lot of governmental support systems, including cheap available all-day care for infants from 3 months of age, in-home care by a nurse if your child is too sick to go to school but you need to work, subsidised cleaning services, and so forth. While parental leave is very limited (4 months for the mother, 10 days for the father, with zero flexibility), the system is set-up to allow parents to go back to work in a full-time basis.

What are the most difficult aspects of balancing parenthood and science?

Major challenges of parenthood:

• The love of my life became my logistics co-manager for the first year. It often felt like every conversation was transmitting critical baby-related information as we did a baby-transfer so the other person could get to work or sleep
• Travel was a major issue. Both my partner and I travel for work once a month, but when a baby is around this turns the other person into a single parent for the week. We both felt guilty about doing this to each other, and I turned down conference and talks that I would normally take – which looked bad on my tenure review
• Illness. Babies are disgusting vectors of disease, and I had non-stop respiratory infections for several years. Normally when you get sick you can just rest and recover, but that is not an option when a baby is around – I had to keep pushing myself beyond the point of collapse. When my son finally started in kindergarten (2.5 years, at which point my partner could take over half the logistics of drop-off and pick-up), I slept for a week to recover.
• Your flexibility becomes very limited – for the first 2.5 years, if I had a faculty dinner or invited speaker event after hours (which happened most weeks), I had to bring my baby along with me. Fancy faculty club dining rooms are rather unused to have a baby around or warming up baby food – and the reception from other faculty was mixed – some were charmed by my son, others strongly disapproved
• The last major challenge was the perception of others, especially the assumption that you cannot be successful at work and raise a child. This was not so much a challenge for me as people tend to (rightly) assume that most fathers don’t actually help that much, but was a major challenge for my partner. Even if it comes from a source of compassion, these assumptions lead to parents not given the opportunity to work on major projects that can lead to promotions

What more could be done to improve the lives of scientist parents? And what single change would have the biggest impact on you? 

Belgium is a good place to start a family, and my partner and I both entered parenthood with a strong agreement on equal parenting. It was much harder than we expected, but in general the support networks were there through government services and our work colleagues. The one thing that really hits hard on scientist parents (although it applies to non-parents) is just the sheer pressure that is placed on us to constantly perform. The career is an immense pressure-cooker, and you are only as good as your last recent success. With so much anxiety and real fear about dropping into a negative spiral (no grant = no paper = no more grants), it is just really difficult to fully disconnect from work to spend the time at home. So I guess if I could change one thing it would be to remove the culture of pressure from science.

What advice would you give to other scientist parents (or scientists who are thinking of having children)?

My advice for new and prospective parents: 

• If you are relocating and you expect to be a parent in the new location, factor baby needs into the decision of where to move to. Will you need IVF, and is this covered by the health care system? Is infant daycare affordable and available, or will one person essentially have to put their career on hold for five years? Is there good financial support for new parents? How about schools? It doesn’t make sense to take a job that pays more if you then have to hand it all back to pay for private schools and health insurance.
• Reduce future commitments in advance. A baby is not a surprise, you have months of notice. You are going to have a major restriction on your time, so start saying “no” in advance. Don’t teach that course, don’t agree to write that minor review, rotate off that committee and say no to reviewing. It is always easy to say yes when the deadline is 6 months away, but the problem is your time is limited and you need to save it for the stuff that actually matters to your career – mainly, big grants and major papers.
• You have to start equal parenting on day one. A long maternity leave can be a self-fulfilling trap – the mother learns how to look after the baby, and as the baby is constantly changing needs, confidence builds. At the same time, the father often doesn’t learn, and never becomes self-reliant. I would really very strongly recommend that new fathers are given substantial amounts of time alone with their child from day one – they need to figure out the same tricks and develop the same confidence that the mother does. Breast-feeding should not be used as an excuse for fathers not to solo parent an infant – babies are able to switch between breast and bottle on a daily basis. The other proviso of equal parenting is that you need to let the other parent find their own method, and not to try to force them to parent the way that you do.
• If you are coordinating baby information between two parents, use an app like BabyConnect, where you can enter all the details so they are available to the other parent (like, when they last took medication), rather than spending your valuable minutes together synchronising care
• Be prepared to delegate at home and at work. You need to reserve time for the important parts, both at home and at work, so delegate away the rest. Hire a cleaner to come in once a week and tidy up the house, so you can spend valuable hours relaxing. Train your post-docs (in advance) to take over your teaching duties – it will be good for their CV and frees up your time at work. Reduce the intake of new students who will need a lot of training, and make sure that your experienced people know when they can make decisions without you.
• Do things for you. It is easy to become focused around the baby and to forget doing the things that made you happy. But a happy parent makes for a happy child, and you will find that you can do anything with a baby that you used to do without one. At the start it can be difficult, but you will soon find your stride and you end up with a family routine that makes everyone happy.

How do you think the challenges of being a scientist and a parent compare with the challenges faced by other professionals who are also parents? 

My partner always says that academics have the freedom to work whichever 60 hours a week they want to. There is a lot of truth to this. The advantage is in the flexibility – I could change my work around the baby logistics at any time. The disadvantage is that I never truly leave my work behind – I am always on call, and always thinking and working.

New post-doc postion available!

A PhD in science is a great career pathway

I've said before that a PhD is a great pathway to unexpected career success. People get so stressed about the academic bottleneck that they forget that there are many other doors that open once you have a PhD. This article puts it perfectly - "Science PhDs lead to enjoyable jobs". Four years out of their PhD, >95% of graduates are satisfied with where their career has taken them, a remarkable figure. So stress less, enjoy your time in research, and you will find your own successful pathway!

The 2018 Golden Pipette Award

Lab retreat 2018: the baton is being passed on, as Dr Oliver Burton, 2017 winner of the Golden Pipette, presents the trophy to Dr Emanuela Pasciuto. Our prestigious prize for the best experiment was awarded for the generation of a transgenic mouse to study brain Tregs.

Having Kids Radically Reshapes Parents’ Immune Systems

Imagine this: The love of your life is 10 inches shorter than you. This being a non-issue, the two of you get on with moving in together and starting a small brood of young humans of your own. Over time, something a little strange starts to occur. You seem to be shrinking just as your partner spurts up. When the dust settles, you maintain the height advantage but the distance between you is cut in half, down to just five inches.

This is analogous to what happens to your immune system when you co-parent. “You are completely changing the cells that constitute your immune system in a way as radical as changing your height,” says Adrian Liston, a researcher at the Translational Immunology Laboratory at VIB in Belgium.  In 2016, Liston was part of the team that documented the physical composition of co-parents’ immune cells shifting to resemble their partners’ cells. Eventually, he says, co-parents end up with more in common immunologically than identical twins.

Are these changes for better or for worse? It’s a tough question to answer, because parenting brings both benefits and deficits. More critically, though, there is no such thing as an ideal immune system — their strength is in their diversity, and between healthy individuals it’s hard to say if one setup is better than another setup. Basically, it depends entirely on the context of what you need your immune system for, and what you need it to do.

It’s clear, however, that becoming a parent changes you fundamentally. Now we know that those changes take effect at the cellular level and define the structure of your inner defense systems. There’s still more we don’t know than we do about how this works, but here are five factors that likely affect it.

 Read the full article in Fatherly.

Congratulations Dr Garcia-Perez!

Today Dr Josselyn Garcia-Perez successfully defended her PhD, and also published an outstanding first-author paper on the genetics of Multiple Sclerosis in Brain. A double congratulations to our newest alumni!

Hoe we de strijd tegen alzheimer en parkinson alsnog kunnen winnen

Ooit spreken we over alzheimer en parkinson in de verleden tijd, beloven onderzoekers van VIB, KU Leuven, UAntwerpen, UGent, ULB en imec.

Farmagigant Pfizer trekt de stekker uit haar alzheimer- en parkinsononderzoek. Patiënten voelen zich aan hun lot overgelaten en wetenschappers zijn ontgoocheld of zelfs boos. Hoe moet het nu verder met de zoektocht naar medicatie? De oplossing moet van heel de samenleving komen.

Verder zonder Pfizer

Dat een reus als Pfizer de handdoek in de ring gooit is een klap. Wereldwijd kampen miljoenen mensen met alzheimer of parkinson, en dat cijfer zal alleen maar toenemen. De boodschap die zij hiermee krijgen is ongemeen hard. In de praktijk betekent het terugtrekken van een van de grootste farmaceutische spelers een fameuze opdoffer voor het uittesten van beloftevolle medicatie in klinische studies.

In die studies richtten farmaceutische bedrijven als Pfizer, maar ook BioGen, Eli Lilly, Roche en Janssen Pharmaceutica, de afgelopen jaren volop hun pijlen op het zogenaamde amyloïde beta. Amyloïde beta klit samen tot de typische eiwitophopingen in de hersenen bij alzheimer. Ondanks miljarden investeringen, bleven die pogingen zonder resultaat. Ook voor parkinson, waar een ander eiwit (alpha synucleïne) zich ophoopt, is er nog geen medische doorbraak.

Het verschil tussen ziek en gezond

Daarom blijven hersenwetenschappers wereldwijd verder zoeken naar nieuwe pistes. We boekten vooruitgang, maar er blijven gaten in onze kennis. Is onze aanpak niet te simplistisch en moeten we juist op verschillende fronten tegelijk werken?

In de zoektocht naar antwoorden, moeten we niet alleen alzheimer, parkinson of andere hersenaandoeningen onderzoeken, maar ook inzetten op fundamenteel onderzoek om beter te begrijpen hoe gezonde hersenen functioneren.

Hoe verschilt de ene zenuwcel van de andere en hoe communiceren ze met elkaar? Hoe worden herinneringen opgeslagen in dat oneindig complexe netwerk? Hoe blijven onze hersenen ‘fit’, en wat doet slaap of veroudering met ons? Pas als we het verschil tussen ziek en gezond écht begrijpen kunnen we op de juiste manier vooruit.

Topprioriteit

Willen we een topprioriteit maken van medicatie én preventie, dan moeten we ambitieus blijven op onderzoek op alle vlak. Dus ook naar de specifieke processen die aan de basis liggen van ziekten zoals alzheimer en parkinson. Hierin boekten wij, en collega’s wereldwijd, de afgelopen jaren belangrijke successen. Via genetische analyse en het ontrafelen van biochemische mechanismen sporen we nieuwe behandelingspistes op. Door te werken aan spitstechnologie (van Vlaamse bodem!) kunnen we ook in het onderzoek steeds een versnelling hoger schakelen. Denk maar aan nieuwe meetinstrumenten, microscopen met superresolutie, meer relevante ziektemodellen en nauwkeurigere analyses tot op het niveau van individuele cellen.

Het talent en de wil is er, maar we kunnen dit niet alleen. We hebben de farmaceutische industrie nodig om onze laboresultaten te vertalen naar experimentele medicijnen en te testen bij mensen. Die verantwoordelijkheid dragen we samen: basisonderzoek brengt nieuwe therapeutische pistes, daarvoor moet de overheid voldoende langdurige en stabiele financiering voorzien. Ook de industrie moet meer gestimuleerd worden om met deze resultaten aan de slag te gaan. 

Door voldoende druk vanuit de samenleving kunnen we alle partners ertoe aanzetten om bij de les te blijven. Om een antwoord te bieden op het groeiende probleem van antibioticum-resistentie, waar industriële partners ook afhaakten, hebben overheden met succes nieuwe mogelijkheden gecreëerd, bijvoorbeeld door het aanboren van nieuwe financieringskanalen en het uittekenen van een beter regulatorisch landschap.

De beslissing van Pfizer moeten we aangrijpen om als samenleving duidelijk te stellen dat niets doen onaanvaardbaar is. We moeten een kader scheppen waarin dit broodnodig medisch onderzoek niet alleen mogelijk blijft, maar net gestimuleerd wordt.

Een raket naar de maan sturen leek eeuwenlang totaal onmogelijk. Aids was een doodvonnis. Kanker onbehandelbaar. Ooit spreken we ook over alzheimer en parkinson in de verleden tijd.

De uitdaging is groot, maar het antwoord heel eenvoudig: opgeven is geen optie.

Patrik Verstreken (directeur VIB-KU Leuven Centrum voor Hersenonderzoek), Christine Van Broeckhoven (directeur VIB-UAntwerpen Centrum voor Moleculaire Neurologie), Sebastian Haesler (directeur NERF, Neuro-Electronics Research Flanders, VIB - imec - KU Leuven), Jo Bury en Johan Cardoen (Managing Directors VIB), Jérôme Van Biervliet (VIB Discovery Sciences). Verbonden aan VIB-KU Leuven Centrum voor Hersenonderzoek: Ludo Van Den Bosch, Stein Aerts, Bart De Strooper (ook Directeur UK Dementia Research Institute), Joris de Wit, Adrian Liston, Joost Schymkowitz, Frederic Rousseau, Rose Goodchild, Pierre Vanderhaeghen (ook verbonden aan ULB). Verbonden aan NERF: Vincent Bonin, Fabian Kloosterman, Aya Takeoka, Alan Urban. Verbonden aan VIB-UGent Centrum voor Inflammatieonderzoek: Roosmarijn Vandenbroucke, Geert van Loo. Verbonden aan UZ Gent: Tim Van Langenhove, Patrick Santens

De Morgan, 13-Jan 2018

An interview with Stephanie Humblet-Baron

An interview between Dr Liesbeth Aerts and Dr Stephanie Humblet-Baron on her recent paper in JACI:

Can you summarize the significance of your findings in a few sentences for people outside your field?

Working in the field of primary immunodeficiency disorders, we described a new mouse model for severe combined immunodeficiency (SCID), recapitulating the key clinical features of SCID patients suffering of both immunodeficiency and autoimmunity (leaky SCID). Importantly our model proposed a novel efficient therapeutic approach for this disease.

What made the paper particularly outstanding?

Due to the pre-clinical evidence of a drug efficiency to treat a rare disease, patient clinical trials can be directly proposed. This treatment is already approved for human use in arthritis, so it could be rapidly be repurposed for leaky SCID patients. In addition, our model is available for further pre-clinical assay, including gene therapy.

When did you realize you were on to something interesting?

When I started to work with this model I already knew which gene was mutated (Artemis). However when I saw the mice for the first time I could tell that they were developing the exact same symptoms that we see in the clinic. I knew that other mouse models working on this gene had never seen leaky SCID symptoms, so I knew we needed to explore in depth the model. The other key moment was after treating our mice with the drug (CTLA4-Ig) – it completely blocked disease, making this a very valuable project with new therapeutic opportunities for patients.

Did the technology available at the department make a difference?

The FACS core was the major technique used for investigation this project.

A huge amount of work and energy must have gone into the paper. How did you cope with stress and doubts?

Liesbeth this is a joker question!

The project went actually quite smoothly, the hard time I got during this project was rather adjusting myself with motherhood and life in science at the same time.

What are you personally most proud of?

This work can be seen as translational medicine, with direct therapeutic benefit for the patients. The ability for better understanding the mechanism of the disease was also valuable to me.

Can you share some advice for others?

Always envision your project as a story to write and tell. When you find a new result ask what would be the next question and continue to explore it further.