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LabListon on Twitter

Entries by Adrian Liston (464)

Monday
Mar092020

Position available to work on diabetes

Great opportunity available for a scientist to work on an exciting diabetes project in the Leuven lab. Pure cell biology / endocrinology, so we welcome applications from beyond immunology! We have a research technician and post-doc position available, depending on the experience / background of the applicant. If you are interested, please apply!

Monday
Mar092020

Team photo

Saturday
Mar072020

Liston lab at work

Tuesday
Feb182020

EXIMIOUS: how does the environment affect our health?

The European funded research project EXIMIOUS sets out to unravel the connections between our immune system and the environment we are exposed to. The Liston lab is proud to be a member of the EXIMIOUS endeavour. 

Each and every day we experience environmental exposures of all kinds, from the air we breathe, the food we eat, the objects we touch, the honking traffic on our way home. Depending on our lifestyle, diet, work and social environments, we all experience a different and complex set of exposures throughout our lifetime. The combination of these, starting as early on as during conception and prenatal phases, during our entire lifetime is defined as the exposome.

The World Health Organisation has drawn attention to the fact that environmental exposures can contribute to the induction, development and progression of immune-mediated, non-communicable diseases, such as autoimmune diseases, allergic diseases and asthma. These are chronic disorders, in which our immune system plays a key role, but for which the underlying causes and prevention strategies are still uncertain. Today, immune-mediated, non-communicable diseases affect about 9% of the European population, with women being two to ten times more likely to suffer from autoimmune diseases than men. If the environment we live in also contributes to these diseases, it is important to know in which way and find a means of prevention.

As of 1 January 2020 the European funded Horizon 2020 research project EXIMIOUS has set out to unravel the connection between the exposome and the immunome (the genes and proteins that make up the immune system), to better understand the role of the environment in immune-mediated diseases. Coordinated by Prof. Peter Hoet from the Katholieke Universiteit Leuven, the 15 EXIMIOUS partners from 7 European countries will collect blood and urine samples from population groups of healthy individuals of different ages, and of patients affected by autoimmune diseases, as well as from population groups with different occupations, such as park workers and miners. This will allow the researchers to build an overview of how different groups of people experience different types of environmental exposures, and how these have an impact on their health. Ultimately, the research efforts of EXIMIOUS aim to provide greater well-being, reduced healthcare costs and improved preventive policies for our society.

“In the EXIMIOUS project, we study how environmental exposures can affect our immune system, possibly leading to a specific immune signature or ‘fingerprints’. We will use these fingerprints as early predictors of immune-mediated diseases,” says Prof. Hoet, who is eager to start working on the EXIMIOUS project with an international and multidisciplinary consortium of experts in immunology, toxicology, clinical medicine, environmental hygiene, epidemiology, bioinformatics and sensor development.

With the ambition and enthusiasm to bring better prevention and help safeguard the health of citizens in Europe and worldwide, the EXIMIOUS team kicked-off the project on 10 February 2020 in Leuven, with representatives of its 15 partners from 7 European countries.

EXIMIOUS is part of the European Human Exposome Network, a joint venture that brings together nine research projects consisting of 126 partners in the largest exposome network worldwide. The EU has committed 106 million euro in funding towards the European Human Exposome Network. On 11 February 2020 in Brussels, EXIMIOUS and its collaborating projects ATHLETE, EPHOR, EQUAL-LIFE, EXPANSE, HEAP, HEDIMED, LONGITOOLS and REMEDIA gave voice to their commitment to work together towards a better and healthier future.

To keep up-to-date on EXIMIOUS’ progress follow @EXIMIOUS_H2020 on Twitter.

About EXIMIOUS The EXIMIOUS project has received funding from the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No 874707. It is a five-year Research and Innovation Action (RIA) that officially started in January 2020 and will end in December 2024. It involves fifteen project partners from seven European countries and has a budget of 10.8 million euro.

Friday
Feb142020

Immune cell treatment offers hope in tackling neurodegeneration

From the Cambridge Independent

 

Thursday
Feb132020

Lab activities

  

  

  

   

Wednesday
Feb122020

Lab dinner

Friday
Jan102020

EU grant success to harness the immune system to treat brain damage

Covered by the BusinessWeekly

Research identifies potential treatment for brain injury and inflammation

Funding awarded to Prof Adrian Liston will be used to advance the approach developed in mice to make it ready for clinical trials. Pioneering research by Prof Liston, a senior group leader at the Babraham Institute, will be developed towards being market-ready for the treatment of brain injury by funding provided by an ERC Proof of Concept grant, as announced today.

Key points:

  • Immunology group leader, Prof Adrian Liston, is one of 76 top researchers to receive an ERC Proof of Concept grant, used to translate EU-sponsored research into the clinic.
  • Research by Prof Liston's team and collaborators developed a method to use the immune system to prevent brain damage caused by disease and injury.
  • EU funding through the European Research Council (ERC) recognises frontier research and provides support to explore the innovation potential of discoveries.
  • This funding will also lead the way towards commercialisation and therapeutic application of the technology.

Research undertaken by Prof Liston and his group has shown that driving the expansion of a specific population of immune cells in the brain is effective at treating brain injury in mouse pre-clinical models. The research shows that this approach is effective at treating brain damage caused by disease, such as occurs in mouse models of multiple sclerosis, or injury, such as occurs following a head trauma or stroke.

Professor Liston, senior group leader in the Institute’s Immunology programme, said: “This is an exciting new approach to preventing neurodegenerative diseases. We have been able to come up with a completely new approach to preventing, and potentially reversing, brain damage. At the moment the treatment is proven to work in mice, with the aim to have it ready for transition to human at the end of the year. The immune system is highly conserved between mouse and human, allowing a high degree of success in translation to the clinical. This is illustrated by the immune-based therapeutics developed in mice now successfully being used in the clinic to fight immunological diseases and cancer. This new method may open up a new immune-based strategy to fight neurodegenerative disease”.

The approach harnesses the power of a type of immune cell called regulatory T cells – cells that control the immune response, suppressing the immune system from over-reacting. Increasing the number of these cells in the brain prevents and reverses the inflammatory damage that occurs to the brain during diseases such as mouse models of multiple sclerosis, traumatic brain injury or stroke. The proof-of-concept research demonstrated that just one treatment was sufficient to prevent brain degeneration and stimulate brain repair.

Image: Pre-clinical testing of neuroimmune treatment in mice receiving a brain injury. The mouse on the left was untreated, and developed neurodegeneration. The mouse on the right was treated, with protection from neurodegeneration. Background image uses immunohistology to visualise signs of active brain repair in treated mice. Image credit: Lidia Yshii (VIB, Belgium), Pascal Bielefeld (University of Amsterdam, Netherlands), Sebastian Munck (VIB, Belgium) and Axelle Kerstens (VIB, Belgium).

“It took a multi-disciplinary and international team, spanning both immunology and neuroscience, to come up with a new approach", Prof Liston said. The grant is based on EU-funded research that was performed at the VIB in Belgium and the Babraham Institute in Cambridge. "We have had a talented team pull out all the stops on this, with particular thanks to Dr Lidia Yshii, Dr Emanuela Pasciuto and Dr James Dooley. Key to the success has been collaboration - working with top neuroscientists across Europe, with Prof Matthew Holt from Belgium and Prof Carlos Fitzsimons from the Netherlands providing key insights and skills".

The research grant from the European Union will support the development of this approach over an 18 month period. The funding will allow for the validation of the treatment in pre-clinical trials and the recruitment of a commercial partner for entry into clinical trials in patients.

Professor Michael Wakelam, Institute Director, said: “It’s fantastic that the ERC have recognised the potential of this promising research. Neurodegenerative diseases increase in likelihood and severity with age, so this research very closely aligns with our mission to improve lifelong health. We’re hugely excited to take the next steps towards developing this approach and exploring the wider instances where this type of treatment may offer benefits.”

ERC Proof of Concept grants award €150,000 to researchers to explore the innovation potential of their scientific discoveries and bring the results of their frontier research closer to market.

Wednesday
Jan012020

Unpopular grant review opinions

Unpopular grant review opinion 1. Sections on ethics, equality, open publishing, budgets, etc make grants almost unreadable, and should not be sent to external reviewers.

I am not saying that these things are unimportant - far from it - just that a data dump of 100-page long applications with 10 pages of actual science is not a useful way to do things. Issues such as open publishing and equality could be better dealt with at the institute level. The institute should have the requirement to show they have appropriate policies in place before anyone from that institute can apply. These are not individual researcher issues. Issues such as budgets are best dealt with by financial administrators. Do I know the appropriate budget for a post-doc in Sweden? No. So don't send me 20 pages of financial material. This could, and should, be checked internally and not sent to external review. Guess what, I also don't read Greek. So why are there 15 pages of internal Greek administrative material in the 68-page document sent to me to review? It just makes my life difficult, and makes it more likely I will miss important bits. I'm also not a fan of letters of collaboration. If you say that you work with someone, I'm going to believe you. It is a weird thing to make up. If I can't trust you on that, why trust you on anything you've written?

Too many funding agencies seem like they want to have boxes X, Y and Z ticked, which is good. Unfortunately, rather than actually check it internally they just want a data-dump passed on to reviewers. Reviewers who are selected for their familiarity with the science, not for administrative sections. This approach looks like the boxes are ticked, but it is not actually a good way of effecting change. It sometimes feels more like a protection for the funder, so that they can say it was checked by external reviewers. 

What do I want as a reviewer? First, a simple log-in that doesn't require me to fill in all my details. Then a small application with just the science. I want an easy-to-navigate website, with just two open text boxes (project and applicant) to fill in. I want practical guidelines on what the scores given mean (e.g., funding chance at each score, solid examples of each score). And that's it. Anything more just makes my life harder. 

Unpopular grant review opinion 2. Reviewing grants is an inherently wasteful way to distribute resources.

Yes, grant review filters out some bad ideas and in theory saves money. But science has to fund ideas that won't work. There is no other way to push back the frontiers.

The main alternative is just bulk funding. Block funding every researcher equally is not ideal either. If there are no penalties for failure and no rewards for success, the system can become stagnant. This is why block funding systems were gradually phased out and replace with grant review. But are systems of 100% grant review the most efficient way to allocate resources? An enormous amount of work goes into writing and reviewing good ideas that are never funded. Would it not be preferable to have some of that time spent on science?

I would prefer it if institutes were required to provide a minimum core funding of 2 junior staff or students to each group leader, with appropriate consumables. Yes, this would take up perhaps 50% of research funding. Yes, limits on group leader hiring would be needed. But under this system, the cycle of insecurity and short-termism would be broken. Small labs could work on hard problems over the long-term. Effort would be spent on research not writing unsuccessful grants.

The pot of funding for research grants would be halved in size, but the number of applications would go way down. I suspect that the actual success rate for grants may even rise under this system. A lot of scientists would be okay with a small team, and might even prefer it. At the moment, a lot of applications are made from a place of desperation, for survival of the lab. Group leaders are constantly trying to grow, because often growth or death are the only options. Those "survival" grants would now not be needed. Grant applications would be reserved for either a) those who have proven their ability to efficiently lead a larger team, or b) the small labs that have a special idea that needs the extra boost in resources.

I suspect that this hybrid system would be more efficient than either 100% block funding or 100% grant review funding. Any funders willing to rise to the challenge?

Unpopular grant review opinion 3. Aspirations to remove the use of metrics, such as DORA  are well meaning, but ultimately cause more problems than they solve.

DORA seeks to remove the influence of journal impact factors. For good reason, since impact factors are problematic, and an imperfect measure of quality of the articles in those journals. But do you know what else is imperfect? Every other system.

I am reviewing 12 grants for the same funder. The applicants have an average of 70 papers each. Let's say that a proper deep review of a research paper's quality takes 3 hours. Just the CV assessment would require 2520 hours of deep review. That is nearly 4 months of work. No one actually does that. Even if we had the time, it would be a repeat of effort already done by the peer reviewers at the journal. 

We also need to acknowledge that metrics have strengths. First, they are less amenable to bias then just having one person say the paper is good or bad. Second, they are better at comparing large numbers of applicants - which is the entire point of grant panels. 

DORA principles have their place. In particular, the faculty selection process. But trying to use these principles on grant review panels does not accept the reality of the job that panel members are being asked to do. I would suggest that grant agencies embrace metrics, but do so wisely and cautiously. Develop a useful set of metrics that are given for each applicant. Some off-the-cuff ideas:

  • average number of last author papers per lab member per year
  • average impact factor of last author papers over the last five years
  • average citation number of last author papers from more than five years ago
  • average amount of grant funding per impact factor point of last author papers
  • number of collaborative papers compared to lab size

I'm not devoted to any of these metrics, but having them would make CV comparison easier and, arguably, fairer. An enormous amount of research should be put into the correct selection of metrics, so that we select for the type of qualities that we want. What you measure is what you get. But the advantages of using metrics are real. We could identify the strengths of the applicant. "This applicant doesn't publish much, but look at the output compared to their funding!" or "Every post-doc who joins this lab ends up with a good paper". Different grant formats could use emphasize different metrics, for example applications for an infrastructure grant should be given a bonus if the applicant has a record of multiple collaborative papers. It just makes sense - they've proven they work with multiple groups. Likewise, post-doc fellowships could be influenced by a metric on their supervisor's success rate with post-docs - I'd rather send a fellow into a lab where most post-docs succeed than to a lab where 90% disappear into the ether. 

There would also need to be a text entry that allows someone to make a case that the metrics are not appropriate in their particular case. I am happy to look beyond metrics if the applicant can convince me there is a reason to. But that should be the case for the applicant to make, rather than throwing out all of the quantifiable meta-data. Blindly using one metric is bad, but intelligently using multiple metrics, tailored to the purpose of the grant, just makes sense. 

Conclusion. We could be doing grant review much better. Right now, I am not even sure that we are moving in the right direction. I'd like to see more involvement from grant agencies, and a more thoughtful assessment of the burden of peer review on both applicant and reviewer. Scientists should just be reviewing the science, and we should be given useful tools to do so. Administrative issues should be audited independently, and often at the level of the institute rather than the grant. These are complex issues, and on another day I might even argue the opposite case for each opinion above, but the important thing is that we should be having a fearless and data-led discussion on the topic. 

 

Sunday
Dec222019

New lab babies!

Congratulations to Dr Kailash Singh and Dr Emanuela Pasciuto, who both had new babies in the past weeks. Lab babies number 12 and 13, respectively!