Three major breakthroughs in the immunology field

31 August 2016
Early 2016 seems like publishing time for the Adrian Liston Group (VIB-KU Leuven). Between February and March, three completely different stories got published. We had a talk with Adrian and James Dooley (Principal Staff Employee), co-first author on the Nature Immunology and Nature Genetics papers and also an author on the Science Translational Medicine paper.

Genetic Predisposition For Beta Cell Fragility Underlies Type 1 And Type 2 Diabetes
Despite being labeled a “lifestyle disease”, diabetes has a strong genetic basis. James Dooley and colleagues in the Adrian Liston group discovered that a common genetic defect in beta cells may underlie both forms of diabetes.

Adrian: “The Nature Genetics paper is really a baby of mine. I started the work 14 years ago when I was a PhD student in Australia. I had seen diabetes in the insHEL male mice, an odd result on what should have been a negative control. My PhD supervisor was not keen on following it up, thinking that it might be an epiphenomenon. I put the project on the back-burner for 3 years during my post-doc, but it was the first thing I started at VIB after moving to Belgium. The paper was actually submitted two years ago; it really took a heroic effort to get through all the experiments suggested
by reviewers.”

James: “The project started when we first began in Belgium in 2009. This has been a strong focus of the lab with almost everyone (both past and present) contributing in some way or another. This also involved a strong collaboration with labs in Leuven and Australia. This is the first paper that demonstrates strong linkage between T1D and T2D showing that beta fitness is pivotal to both.”

Publication
Dooley et al (2016) Nature Genetics

The Cellular Composition of the human immune system is shaped by age and cohabitation
The research took a detailed look at the immune systems of 670 people to understand more about what drives variation in our immune systems between individuals. From an assessment of the effects of a range of factors, including age, gender and obesity, one of the most potent factors that altered an individual’s immune system was whether they co-parented a child.

James: “Extreme care was taken during this project to optimize all aspects of the protocols. We needed to understand the effects of time, temperature and limitations that were in place. To do this we needed to use a single individual, as there is substantial variation from person to person, and to evaluate the effect of temperature as the clinic and lab space are substantially variable depending on the time of year. We also had limitations as to when and how long it would take for the blood to get from the clinic to the lab so we needed to evaluate and develop criteria that could be applied to all samples to minimize variation between individuals. Finally, developing a robust multi-parameter flow cytometry based platform required testing of many different antibodies in various combinations.

Adrian: “When I say that James made the study happen through his blood, sweat and tears, I mean that rather literally. To set up the study, James was bled every few hours to look at how different processing protocols would alter the results. Then during the four years of the study, James was bled dozens of times to give a standard control. We even had him bled for the TV, so that VTM could get some good visuals.”

Publication
Carr & Dooley et al. (2016) Nature Immunology

Familial autoinflammation with neutrophilic dermatosis reveals a regulatory mechanism of pyrin activation
A mysterious inflammatory disease has been afflicting a Flemish family for three generations, causing severe skin lesions, fevers, pain and exhaustion. Research by Adrian Liston and colleagues has found the genetic mutation and also identified an effective treatment.

Adrian: “We have been working on a lot of different patients with inflammatory disease. Quite often we end up with new biological understandings from assessing these patients, but it is relatively rare that we can immediately use this information to redesign a treatment. It is quite odd for a biomed scientist actually. Normally we are so used to thinking “maybe in 10 years someone will use this information to make a new drug, which will take another 10 years to come out”, so having an actual immediate impact on people’s lives is humbling.”

James: “Working previously in the emergency room I had missed seeing the immediate results of my efforts. Although we are working on many patients, every case where we are able to find something that can help a patient is truly motivating and keeps us striving to solve each case. This work is the result of a strong collaboration with many people involved. In this case it was not only possible to discover the cause of the disease but a cure too. Anytime that you are able to do this, it is something remarkable.”

Publication
Masters et al. (2016) Science Translational Medicine

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In 2016 Eppendorf Ag, The Hamburg Life Science Company Awarded Adrian Liston its highly prestigious research prize.
The Jury: “Adrian Liston’s experiments have paved the way for understanding key steps in controlling regulatory T-cells that are critical for balancing between autoimmunity and immunosuppression. His work opens up the way for new therapeutic approaches towards diseases resulting from a dysregulated immune homeostasis.”

Adrian Liston: “I am thrilled to learn that I am to be awarded the 2016 Eppendorf Award. A great recognition of the work done by all of the amazing people in my lab!”


James Dooley and Adrian Liston