Congratulations to Ntombizodwa Makuyana

Congratulations to Ntombizodwa Makuyana, for winning the Babraham Institute prize for best poster by a first year PhD student!

A great start to a high potential PhD!

My Life in Science

An old talk I gave on my scientific career, with an emphasis on being a parent scientist and on my experience in seeing sexism in action in the academic career pathway:

Congratulations Dr Steffie Junius!

Congratulations Dr Steffie Junius, for achieving a successful PhD! Steffie has just completed an ambitious graduate program, studying the plasticity and fragility of regulatory T cells. It has been a pleasure watching Steffie grow into a successful scientist. Like every PhD, it had its ups and downs, its challenges and highlights, and I'm incredibly proud of how Steffie handled the entire process. I just wish I could have been there in person to celebrate her big day!

Dr Junius is now moving on to an exciting position as post-doctoral researcher at Janssen. Her major thesis work on regulatory T cell plasticity will hopefully come out soon - it is an elegant study with major implications for the design of cell therapy approaches using regulatory T cells. Well done Steffie!

Congratulations to Julika Neumann!

CCongratulations to the very talented Julika Neumann, who successfully defended her application for a competitive FWO PhD fellowship!

Just starting her PhD, Julika already has several major successes under her belt, including identifying a new primary immunodeficiency (stay tuned!) and spear-heading an open science study on COVID pathology.

We anticipate more great successes from Julika during her FWO fellowship!

Congratulations Dr Erika Van Nieuwenhove!

A huge round of congratulations for Dr Erika Van Nieuwenhove, who successfully defended her PhD. Erika set for gold standard for PhD defences, with an outstanding presentation and masterful question time. Erika's thesis was on inborn errors of immunity, with her PhD covering multiple new genetic mechanisms for PIDs, including mutations in ADA2 and Ikaros, plus a machine learning-driven approach to the diagnosis of JIA. The work is not yet finished either - stayed tuned for more Van Nieuwenhove papers on new genetic causes of neutropenia! A future leader in pediatric immunology and rheumatology!

Dr Lidia Yshii wins Golden Pipette

Congratulations to Dr Lidia Yshii for winning the 7th Golden Pipette at our joint Leuven-Cambridge lab retreat held at the Babraham.

The most elegant experiment is always a tough call at our lab retreat, but it is hard to go past a simple treatment that blocks 90% of the damage during traumatic brain injury!

Looking forward to accelerating this treatment into the translational space. 

Dokter Algoritme

Algoritmen kunnen inzichten bereiken waar een mens moeilijk toe komt. Computeralgoritmen kunnen almaar beter moeilijke diagnosen stellen, soms zelfs beter dan artsen. Immunologe Erika Van Nieuwenhove van de Leuvense tak aan het Vlaams Instituut voor Biotechnologie (VIB) en haar collega’s melden in Annals of the Rheumatic Diseases dat ze een zelflerend algoritme hebben ontwikkeld dat met bijna 90 procent zekerheid artritis bij kinderen kan vaststellen, louter op basis van een bloedtest.

Het gaat om de vaakst voorkomende vorm van reuma bij kinderen, maar omdat de ernst en de evolutie van de symptomen sterk kunnen variëren, is een diagnose stellen niet altijd gemakkelijk. Het algoritme evalueert alleen de samenstelling van het immuunsysteem van de patiënten. Het zal nuttig zijn om te bepalen welke behandeling aangewezen is.

Knack - 24 Apr. 2019 - Page 86

Is the Scandinavian model the solution for STEM parents?

The Scandinavian model for parental leave is often touted as the world’s best. 12 months parental leave, split between both parents. This is a great model for a lot of careers, but is it actually a part of the solution to the issues that women face in the STEM fields?  In some cases, perhaps, but as a blanket solution I find it lacking:

1)     First, it must be stated that extended parental leave is only part of the Scandinavian model. When it was first legislated, the leave was typically taken almost exclusively by the mother, with the father just taking the mandated “Daddy’s two weeks”. Essentially, it reinforced the traditional model that put parenting on to the woman, often truncating women’s careers. This has changed substantially over the years, but those changes are due to the evolution of Scandinavian culture and the increasing normality of equality in the Scandinavian countries. Implementing just extended parental leave will not recreate the full advances seen in women’s careers across Scandinavia in the past decade

2)     Extended parental leave is ideal for workplaces where workers can be readily replaced during this period. Large employers are capable of hiring extra staff which can shift between different positions, and employees that only need days or weeks of training to get up to speed are easier to replace. Academic science generally fulfils neither of these categories. First, while universities are large, labs are essentially independent small businesses. Few if any labs are large enough to have standing rotating staff that substitute in for parental leave. Second, for scientific staff, their skills require months or years of training. As an employer, I generally write off the first 3 months of a post-doc’s time as just getting up to scratch of new techniques and the project. For a Masters student starting a PhD, often the entire first year is spent mastering the field without actual productive experiments being performed. That level of expertise is just not readily replaceable, which means the science suffers. This will then leave a negative mark on the applicants' CV beyond the one-year gap.

3)     Scientific funding and scientific projects rarely have the flexibility to make this work. Consider a PI who hires a post-doc to work on a 3 year project. One year into the project, the post-doc goes on maternity leave for a year. The PI cannot put the project on hold for a year – since the funding clock is still running. Instead they need to transfer the project to a new person. Is it fair or reasonable for that project to be transferred again when the parental leave post-doc comes back? Potentially, but it is something that needs to be solved on a case-by-case basis. Even if the funding could be put on hold for parental leave (as in some fellowships), scientific careers are built on advancing science. If the work is scooped in the meantime, original work becomes confirmatory work – which would be a negative for the lab, the PI and the post-doc.

Consider two hypothetical cases, and whether extended parental leave helps or hinders a woman’s career in science.

Scenario 1. A young female PI goes on extended parental leave. What happens to her lab? You can’t shut the lab down for a year. PIs have responsibilities to their students and post-docs, they have responsibilities to their grant funders. So either those students get shuffled to another PI, or they have to work independently (and sub-optimally), or the PI on leave actually spends a chunk of unrecognised time managing the lab remotely. After the return, authorship on papers can often become murky and grants have been spent inefficiently.

Scenario 2. A young post-doc employed on a grant goes on extended parental leave. The PI hires a replacement post-doc to continue the project (the grant and science must go on). A year later the post-doc returns and (best case scenario) the PI manages to find enough funding to keep both staff on for a year to finish up. The paper may end up with a joint-first authorship, or maybe the new post-doc was able to push things fast enough that the original post-doc becomes second author. Afterall, the year back after parental leave is hardly your most productive. There is no easy fix – the PI needs to consider the contribution of both staff members in making a decision.

In short, I think that the Scandinavian model is excellent, and an incredible advance for some careers. However the particular aspect of extended parental leave is not suitable for all people (not everyone wants it), and it can have a negative effect on STEM careers. I would suggest a more flexible approach to STEM researchers who have children. This approach would allow researchers to make the choice to take extended leave, or make the choice to stay active in their field:

• Extended parental leave should be an option available to all
• Implement broad structural changes that promote equality in STEM, most importantly hiring women at senior levels and normalising a healthy life balance
• Infant daycare and before/after-hours childcare should be cheap and readily available for parents who chose that pathway.
• A “parental sabbatical” should be available to PIs who have children, where the PI becomes excused from all teaching and committee duties for a year, but is still able to work on research
• Grants should be automatically extended by a year if the PI has a child or if the staff paid on those grants go on leave
• Ethics protocols, biosafety protocols, etc should be automatically extended by a year if the PI has a child or the staff working under those protocols go on leave
• Review board decisions should be delayed by two years if a PI has a child
• Please comment if you have additional suggestions

If you are interested in how my family handled having a child and a career in STEM, you can read an interview I had with eLife on being a scientist parent. 

Congratulations to Prof Humblet-Baron!

Congratulations to Dr Stéphanie Humblet-Baron, who was just awarded the prestigious (and highly competitive) BOF-ZAP award. With this award Stéphanie starts a tenure-track research professorship and her own independent group.

The success of both Prof Humblet-Baron and Prof Schlenner at the BOF-ZAP awards puts the Translational Immunology laboratory in a great position. Going forward from my move to the Babraham, Prof Schlenner is leading the mouse immunology research and Prof Humblet-Baron is leading the clinical immunology research program.

Leaving two such talented and determined women to take over my lab, and push it to new heights, is my proudest legacy of 10 years in Leuven.

The Humblet-Baron team will develop and use cutting-edge systems immunology approach to study the many diseases in which the immune system places a key role, from primary immunodeficiency to infections to cancer to neurodegeneration. Watch out for great things new Prof Humblet-Baron is here!

Stephanie Humblet-Baron tackles one immune disease after the other

In two recent studies, the same team of scientists has uncovered the mechanisms underlying two distinct immunological disorders affecting both children and adults. Stephanie Humblet-Baron(VIB-KU Leuven) was the researcher at the helm of both projects.

A pediatrician by training, Stephanie Humblet-Baron is building a career unravelling immunological disorders that affect children. She divides her time between the clinic and the lab, where she is a senior team leader in the lab of Adrian Liston (VIB-KU Leuven).

From disease to biology and back again

Ever since the start of her medical training, Humblet-Baron developed a special interest in unraveling the biological mechanisms that cause immunological problems. Many immune diseases are poorly understood, and this lack of knowledge also limits treatment options and choices.

“People sometimes refer to these diseases as rare,” says Humblet-Baron, “but we all carry risk factors for many immunological diseases. Even if a given mutation is rare, the accumulated variation in immunological responses affect a broad set of outcomes, for example how someone responds to cancer treatment or drugs for cardiovascular conditions. That is why understanding the mechanisms underlying immune-dysregulation is so important.”

In her most recent work, Humblet-Baron, together with her colleagues in the lab of Adrian Liston (VIB-KU Leuven), focused on the mechanisms causing myeloproliferative disease and hemophagocytic lymphohistiocytosis, two diseases that are fatal unless given aggressive treatment.

Myeloproliferative disorder: a partner in crime for dendritic cells

Dendritic cells are specialized antigen-presenting cells that play a crucial role in coordinating innate and adaptive immune responses. In both patients and mice, depletion of dendritic cells leads to myeloproliferative disorder, but how or why—no one really knew.

“To understand what was going wrong, we created a mouse model where dendritic cells were present in normal numbers, but were functionally impaired,” explains Humblet-Baron. “We found that without the antigen-presenting capacity of dendritic cells, the mice developed myeloproliferative disorder.”

The team uncovered that it was not the number of dendritic cells, but their partnership with CD4 T cells of the immune system that was crucial for disease development. When CD4 T cells were absent as well, the mice showed no symptoms of myeloproliferative disease.

This has important implications for patients, where specific mutations also manifest both dendritic cell deficiency and myeloproliferative disorder. “Based on the original model disease model, the proposed line of treatment would be dendritic cell replacement, currently only possible through bone-marrow transplantation,” says prof. Adrian Liston. “But these new results indicate that attenuating the activatory signal from CD4 T cells could also reduce the development of myeloproliferative disorder.”

Hemophagocytic lymphohistiocytosis: New light on a deadly disease

Hemophagocytic lymphohistiocytosis, HLH for short, is a severe disease less than 2 out of 3 patients survive. It can be triggered by a variety of factors, including genetic defects, viral infections, anti-tumor responses or unchecked autoimmunity. Excessive production of interferon γ was assumed to be the key pathological step, but based on patient evidence and a pre-clinical mouse model of the disease, the Leuven research team has now found that there is much more to it.

Humblet-Baron: “We found that the production of interferon γ was only responsible for part of the features of the disease. Excessive consumption of the immune signaling molecule interleukin 2 by hyperactivated CD8 T cells, the suppressor cells of our immune system, had a much greater impact on the inflammation.”

This means that at least two different disease pathways are at play—knowledge that indicates that we could save the lives of more patients if we also targeted both pathways during treatment.

“This study not only provides a new paradigm for understanding HLH, with major implications for its treatment, but also gives us a broad insight into how hyperactivated CD8 T cells cause damage,” adds prof. Adrian Liston.

“We can learn so much from an in-depth analysis of the immune cells present in a simple sample of blood from patients,” concludes Humblet-Baron, who hopes to uncover the mechanisms underlying many more of these immunological problems. “Coupled with the power of biochemical and animal research, these insights are really changing how we diagnose and treat patients in the clinic.”

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Humblet-Baron, et al 2018 Blood. "Murine myeloproliferative disorder as a consequence of impaired collaboration between dendritic cells and CD4 T cells"

Humblet-Baron et al. 2018 Journal of Allergy and Clinical Immunology. "IFN-γ and CD25 drive distinct pathological features during CD8 T cell hyperactivation in hemophagocytic lymphohistiocytosis"

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