Immunology expert Prof Adrian Liston elected Fellow of the Academy of Medical Sciences

Key points:

Postdoc job opportunity in the lab

Happy to say we have a great job opportunity to join our lab! The position is for a bioinformatics or datascience postdoc position, starting in the Babraham Institute. The position is to lead the data analytics of the Eximious Horizon2020 project. An amazing opportunity to unravel the real-world link between environment and immunity, using the largest and most comprehensive datasets to yet be generated. I welcome applications from thoughtful scientists willing to learn the biology and search for the most appropriate computational tools to apply. Time is provided to learn and develop new skills, so consider applying even if you don't perfectly align to the project. Come join us in Cambridge! 

Apply here. 

How to keep your virtual lab meeting from being just another Zoom call

Terrific write up at Cell Mentor on virtual lab meetings. I had the pleasure of discussing our zoom retreat with Claudia Willmes for the article, and could describe all of the fantastic activities designed by our lab social team to keep everyone engaged. The whole article is worth reading, but a highlight is the call-out to Ruben's excellent escape room:

Escape games were already a popular activity for lab outings before 2020, but they have been taken to another level during the pandemic. There are several escape room companies that offer virtual adventures. Liston's group took this a notch further and went for a custom-made game designed by lab member Ruben Vangestel.

"The custom escape Zoom was based in the lab cold room, with a series of puzzles needed to escape," Liston says. "It had the typical ‘communal problem solving' aspect of an escape room, but by using pictures of our lab as the setting and cameos from lab members giving clues, it really created a warm feeling of togetherness. A reminder of the space we used to share, and the common experiences that unify us."

A cynic's guide to getting a faculty position

I gave an academic caeer talk yesterday at the University of Alberta, and on request from the students I am putting the talk online. These are my personal thoughts on how the job selection process works for independent research positions in universities or research institutes, based largely on my experience, the experience of my trainees going through the process and my observations of behind-the-scenes job committee meetings. I am sure that there is enormous variation in experiences, and that systems work differently in different places: hearing the perspective of many people is more valuable than just hearing the perspective on one.

I'd also just note that this is not an endorsement of the system as it exists. There are aspects of the system that I dislike and actively work to change. But I still think it is valuable for job seekers to understand the system, warts and all, rather than believing in an aspiration system that has yet to materalise. I often hear from trainees that they career training is largely directly to non-academic careers, and they rarely hear how the academic pathway works. So, with a little too much honesty, and an expectation of landing in hot water, here is my attempt to open a conversation:

Thesis acknowledgements

It is so lovely to read the words of graduating students in their thesis acknowledgements. I've seen them learn and grow over the years, increase in skill and resiliency, reach depths they didn't know they have. And here they are, just leaving on to their new adventure and they stop to write kind words back to us.

These from (soon to be) Dr Steffie Junius:

Next, I would like to thank my co-promotor Prof. Adrian Liston. While on paper you’re addressed as my ‘co-promotor’, I truly perceived this as rather having two full promotors who both guided me in their own way, complementing each other. I still remember the evening in Boston when I received the email with an offer to start a PhD at your lab. The thrill to be accepted in such an environment of excellent science made me excited to become the best possible immunologist I could be. Throughout this PhD you have guided me with your advice and mentorship. Especially on the dark moments, you always were able to push me in the right direction and to follow through even when I did not know how. As PhD students, we always think the science is the most important part of a PhD, but you made me understand that personal development is just, if not more, important to becoming truly successful. Thank you for your advice and guidance over the years. The lessons you taught me will stay forever with me throughout my career. 

Thank you Steffie, it has been wonderful to be part of your journey. Enjoy the next stage of your career!

Mo Siewcharran Prize to Tenmei

Lovely news that the talented Tenmei won a Mo Siewcharran Prize at the FAB Prizes, discovering new talent and promoting under-represented authors, for her beautiful illustrations in "Battle Robots of the Blood". Gorgeous detail throughout, but my favourite picture is perhaps the evocative eyes staring at an embarrassed Tim. Prize well deserved!

Battle Robots of the Blood reading

Me and Hayden read "Battle Robots of the Blood" together.

Covid-19 vaccines: Discussing how they work, the second dose and timing with Babraham Institute immunologist

Vaccination offers by far the best – perhaps only – route out of the Covid-19 crisis.

And, with two vaccines now being rolled out in the UK and a third available in the spring, progress is being made on delivering this vital protection.

Immunologist Prof Adrian Liston, at the Babraham Institute, tells the Cambridge Independent: “Vaccines all work in a fairly similar way. The key outcome we want are antibodies that bind the infecting virus and either block its entry to cells or flag it for destruction."

read the interview with me here

 

As an aside, back in May 2020 I was interviewed on the prospects of a COVID vaccine. Unlike some other experts, I argued that the first COVID vaccines would likely be designed, tested and approved by the end of 2020, and that the regulators would accept a vaccine efficacy rate as low as 50%. Fortunately my optimistic forecast proved true, with the FDA issuing guidence in June that they would accept efficacy rates of 50% and above, and the first approvals occuring in December 2020. Hopefully my optimism on the dosage change proves equally prophetic!

European “ImmunAID” project for the diagnosis of rare autoinflammatory systemic diseases launched in Belgium

The project wishes to diagnose rare autoinflammatory systemic diseases through the identification of biomarkers

In December 2020 a new project has been launched in the University Hospitals Leuven. The ImmunAID project aims to identify new tools for the diagnosis of systemic auto-inflammatory diseases (SAID). SAID are a complex and evolving group of rare diseases characterised by extensive clinical and biological inflammation. These conditions are caused by a dysregulation of the innate immune system leading to a release of immune cells and mediators provoking fevers, tissue and organ inflammation and damage.

Sometimes it is difficult for the physicians to make a correct diagnosis, since the main symptoms of these diseases (such as fever, rash, joint pain, etc.) are also present in many other conditions. Thus, a patient may have received on average up to 5 inappropriate or ineffective treatments before being properly diagnosed, having a great impact on their health and quality of life. The aim of ImmunAid is to understand the mechanisms that drive the pathology in order to provide better diagnosis and care for patients with these rare but potentially devastating diseases.

An unprecedented body of clinical and biological data in the field of SAID

This new project aims to find new and more effective ways to diagnose SAID. While it is already known that some SAID are due to specific genetic mutations, a large number of SAID can only be detected by a set of clinical signs and symptoms and after other diagnostic possibilities have been excluded. Since SAID are rare conditions, a large group of patients suffering from various SAID is being recruited throughout Europe. As such, the ImmunAID cohort represents a very important tool for researchers defining biological fingerprints, or biomarkers, specific to distinct SAID.

The team expects to find a set of biological features common to all SAID, which will allow to quickly confirm or refute the diagnosis of suspected autoinflammatory syndrome. In addition, for each SAID, a list of characteristic biomarkers and an algorithm will be generated to allow the physician to make an appropriate diagnostic assessment.

In order to achieve the project's objectives, biological samples collected from the patients will be analysed in a European-wide research network by set of state-of-the-art technologies and will generate an unprecedented amount of data (genomics, transcriptomics, proteomics and microbiome). Simultaneously, other analyses will focus on immune cells, molecular mechanisms and specific agents of the immune system (cytokines, etc.). All data generated will be subjected to artificial intelligence and modelling analysis.

Prof. Carine Wouters, paediatric rheumatologist at the University Hospitals Leuven, is highly committed to the success of the project "We are delighted and proud to be able to work with ImmunAID partners as it represents a unique opportunity for the European scientific community to advance research in an important field of rare diseases that can only be tackled at large scale. We will do our best to come up with meaningful results that will improve patients’ diagnosis and medical care.”

Leuven teams are the forefront of the project

The teams of the Leuven University Projects are at the forefront of the project. The activities carried out in the Belgian centre will be two-fold. First, the team from professor Carine Wouters and professor Steven Vanderschueren will be in charge of recruiting patients suffering from monogenic SAID (FMF, CAPS, TRAPS, MKD) or genetically-undiagnosed SAID (Still disease, neutrophilic dermatosis, Schnitzler syndrome, Takayasu arteritis, Kawasaki disease, Behçet disease, chronic osteitis, recurrent pericarditis and chronic systemic inflammation of unknown origin).

Second, professor Wouters, professor Patrick Matthys and professor Paul Proost from the Rega Institute and KU Leuven department for Microbiology, Immunology and Transplantation will be involved in the biochemical and biological analysis of the samples. The team of Carine Wouters and Patrick Matthys will apply their extensive knowledge on Natural Killer cells to identify and characterize their possible altered activity in SAID patients. On the other hand, the team of Paul Proost will study whether modifications of messengers of the immune system (cytokines and chemokines) in patients play a role in regulation of the inflammation processes. The team of professor Stephanie Humblet-Baron and professor Adrian Liston will analyse in-depth the immune cellular compartment of the blood of affected patients in addition to genetic investigation in order to identify new genes responsible for SAID.

These activities are intended to gain insight into the mechanisms triggering the aberrant behaviour of the autoinflammation process. The results will be pooled with other analyses from other European research laboratories to help identify biomarkers of the diseases and possible therapeutic interventions.   

Regarding the ImmunAID project: ImmunAID is a research project (www.immunaid.eu), which aims to identify a set of disease-specific biomarkers to confirm the diagnosis of SAID. ImmunAID is implemented by a large consortium (25 partners in 12 European countries) and has been funded with € 15.8 million by the European Commission. The ImmunAID project has received funding from the European Union's Horizon 2020 research and innovation programme under Grant Agreement No. 779295.

IL-2 cytokine networks

If anyone is interested in our lab's work on IL-2 cytokine networks, I just gave a seminar on the topic, which I am putting up here:

It is a new talk for me, and was an interesting one to write. I started to work on IL-2 right at the start of my PhD. I was very keen to return to the topic when I opened my own lab in Belgium (2009), with one of my first PhD students (Dr Wim Pierson) working on the niche-sensing and niche-filling negative feedback loop that provides a stable number of Tregs in the system. (An excellent collaboration with one of my favourite immunologists, Prof Daniel Gray from WEHI, Australia).

Then Prof Stephanie Humblet-Baron joined my lab for a post-doc, wanting to work on a disease known as Familial hemophagocytic lymphohistiocytosis (FHL). At the time, this was thought to be a disease of CD8 hyper-activation and IFN-gamma. Thanks to great work by Stephanie, in mouse and human, we now know that FHL is only partly driven by IFN-gamma, and instead a key part of pathogenesis comes from flipping the negative feedback loop between IL-2 and Tregs into a postivie feedback loop between IL-2 and CD8 T cells.

Right back in 2009 we started to work on a new genetic switch that would let us turn IL-2 on in different cell types. At first I just wanted to see what would happen if Tregs could make their own IL-2. By breaking that dependency on exogenous IL-2 do you get a run-away Treg reaction? (answer: yes, yes you do). Once we finally made the mice, however, it just opened so many different doors. What happens if CD8 T cells make their own IL-2? How about NK cells, dendritic cells, B cells? What if we turn it on in different organs? It has really been a phenomenal mouse that just kept on delivering interesting results. Dr James Dooley led a team working on the mouse, and more recently Dr Carly Whyte drove the project to publication. Or, at least, pre-publication - you can see the paper here on BioRxiv. So many interesting aspects of IL-2 biology were illuminated by this work - easiest to show in a circuit diagram:

I hope you enjoy the seminar. Keep an ear out for the muffled bang at the 29 minute mark. It doesn't sound like much on the audio feed, but across Cambridge we all jumped up as the windows rattled and the building shuddered. I fumbled the graph on this slide, calling Tregs Tconv by mistake, wondering if an explosion had gone off downstairs. Fortunately it was just a sonic boom as fighter jets scrambled overhead.