Lafferty debate, ASI

One of my favourite events of the scientific year, the humorous Lafferty debate at ASI 2019. 

This year, the value of mouse research. Fantastic points put forward on the incredible value that mouse research has given to immunology. Right now it is popular to diss mouse work, but it is worth remembering that almost the entire basis of immunology - the cell types, the immune responses, the origin of immune diseases - is based on mouse immunology. Yes, there are some differences between mouse and human, but the incredible advances in treating immunological diseases have come from work that developed in mouse. Parallel mouse-human research is the only method that has actually cured disease, so let's not throw out the winning formula.

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!

Interview with Louisa Wood

 Where were you and what were you doing before you joined the Institute?

I was a professor at the University of Leuven and VIB, in Belgium. I set up my lab there in 2009, and spent the last 10 years growing a research program and setting up two core facilities. 

What has the relocation experience been like so far? Best bit and worse bit?

I might plead the fifth there! Problems are for solving, not complaining about. 

What’s your research about?

I've always admired scientists who chose one problem and spend a career on solving it at a deeper and deeper level, but that isn't my personality. I love the creative process, hearing about a problem and them coming up with a spark, a creative way to tackle that problem. It has been a fun way for me to work, and we've made major contributions in different fields - basic immunology, clinical immunology, endocrinology, microbiology, neuroscience, genetics, bioinformatics - but I've generally avoiding asking the follow-up questions. I think as my career has matured, I might be ready to settle down with that one special question through: what is the adaptive immune system doing in the tissues? 

Any advice from what you’ve learned from setting up your own lab?

There are different routes to success, and you need to find one that works for you. From my perspective, the key to my success (survival? I guess they mean a similar thing in academia) has been rapidly building a diverse portfolio. Key here was my first hire - James Dooley (still with me 10 years later, having relocated over to the Babraham with me). He came on as an experienced research assistant from a small lab (an amazing training ground, since techs in small labs are expected to know how to do everything). Having someone that I could trust in the lab let me write grants. I wrote and wrote and wrote - I brought in 22 grants and 19 fellowships over my 10 years in Belgium, and must have submitted one a month on average. The whole time I saw James develop as a lab manager and then a senior scientist, and saw that he was actually much better in the lab than I ever would be, so the relationship turned into a partnership, with each of us taking the lead in our area of expertise. So I guess the key advice would be to hire James - but he already has a job, so hands off! Seriously though, hire the best, give them your trust and support, and let them take on responsibilities as they grow. It means making a serious commitment to their careers: senior staff grow more valuable every year, and this should be reflected in their salary and job stability.  

Do  you  have  any  words  of  wisdom  for  those  starting  off  in  a  scientific career? What do you know now that you wish you’d known then?

First, attitude matters when you hire someone. Unfortunately, not everyone is in science because they care about it. I've had people with very competent CVs join my lab for the wrong reason, like wanting to get a PhD. Ultimately, if you don't really care about the science, you won't be a good scientist. Skills can be taught, but I've never found a good way to mentor someone who didn't have a positive attitude, so my advice to a younger me would be: when you see those warning signs, give that person their notice. Attitude also matters in the other direction: when we needed to hire a mouse technician we passed over people with experience to take on Jeason Haughton, a Jamaican life guard with no experience in science at all. Why? Because we could tell that he was ready to listen, ready to learn and ready to work. Jeason has now been with me for 6 years, and there was a long line-up from other labs desperate to take him on when I moved over to Cambridge!

Second, peer review is over-rated. There is a degree of "reviewer roulette" at play that you can't take too personally. Great grants get rejected all the time. My first small grant to a Belgian funder was rejected - a few months later I submitted more-or-less the same thing to the ERC and gained a €1.5m grant that led to great papers. Papers will get rejected at one journal, and then accepted at a better journal. Why? Reviewer roulette. Oh, there have certainly been occasions when a reviewer's suggestions improved a paper, but more often it is just extra stuff for the supplementary material. My advice is to accept it is a game, and win through numbers. Why invest all your emotional energy into one grant, when you can write four or five? If a paper is rejected from one journal, resubmit to the next that day. Start juggling with as many balls as you can competently handle (the trick is working out how many that is), and make sure they are always in motion. 

Who has inspired you? Why?

David Attenborough. From the youngest age, watching his documentaries guided me into thinking like a scientist. To try to understand life through the prism of evolution, to understand living systems as complex positive and negative feedback loops. I still find that I bring a very ecological style of thinking to understanding immunology. He also shaped by ethics and my politics - because of him, I am a lifelong vegetarian and ardent environmentalist. For an inspiration from an immunologist, I've also admired the work of Gitta Stockinger (now at the Crick). Someone who is prepared to do a deep-dive into a question, and not just crop off the easy big hits: her work on Th17 cells and the aryl hyrdocarbon receptor are some of the best reads in the field. I'd also add: I think it is important to tell people how much you admire them! Science is a tough business, and even the most senior people deserve positive affirmation. I had the pleasure of successfully nominating Gitta for an EFIS-IL award in 2017, and it was a pleasure to introduce her award plenary and describe her to everyone as one of my scientific heroes. Just recently I sent a letter to Sir David, thanking him for his influence (and received a nice reply too). 

What has been your proudest personal and/or scientific achievement?

Here I would bring up two post-doctoral fellows who joined my lab back in Belgium - Stephanie Humblet-Baron (joined 2010, as her first post-doc) and Susan Schlenner (joined 2012, as her second post-doc). Both are amazing scientists, Stephanie as a clinical/translational immunologist and Susan as a molecular immunologist, who took on slow-burning projects. For Stephanie, it was six years between her starting in my lab and getting her first paper - but since then a big hit every year! Susan not only started ambitious projects but also set up a CrispR facility at the University of Leuven - a job that has helped many labs, but is not exactly a career builder. In both of them I saw future leaders. They were already at an amazing level scientifically, so my mentorship was to help build their understanding of how a lab works, strategies for writing grants and papers, discussions on how to manage staff, advice on how to build and maintain a portfolio of projects, and guidance through the tenure-track application process. So among my proudest scientific moments were when they were both made tenure-track professors at the University of Leuven - Susan in 2017 and Stephanie in 2019. Two outstanding scientists from my lab who are now independent. I don't think I could have left Belgium without knowing that my lab and Core facilities there would continue to flourish, now under their leadership.

PhD opportunity in the Liston lab!

Are you interested in a PhD in neuroimmunology? Want to find out how to harness the power of the immune system to cure traumatic brain injury? Check out our PhD position here. It is a rare chance to join a fantastic international team, and to learn to do high level science in a supportive and caring environment.

A successful candidate will be:

• passionate about science and the project
• experienced at failure, with a track-record in the resilience needed to pick yourself up and try again
• willing to be wrong, willing to learn, willing to improve
• driven to make a difference, discover new biology or move a promising therapeutic to the next stage
• creative and imaginative
• detail-orientated and reliable

The successful candidate does not need:

• experience at immunology or neuroscience. You are here to learn, not start as an expert!
• technical experience in X, Y or Z - as above
• a perfect CV. I'm interested in seeing that you know how to succeed in the face of adversity

 If you are submitting an application, consider a co-application to a Cambridge College, such as Peterhouse.

Liston lab

Farewell to Julian Behr

A big farewell to Julian Behr. Julian has been an amazing Masters student this year. Our first Babraham alumni is now off to start his PhD with Maries van den Broek at the University of Zurich. Expect great things!

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. 

Scientific heroes

My first scientific hero was Sir David Attenborough. From the youngest age, his documentaries guided me into thinking like a scientist. To try to understand life through the prism of evolution, to understand living systems as complex positive and negative feedback loops. David Attenborough inspired me to become a biologist, and shaped my politics and my ethics. I recently wrote to him to thank him for the profound effect he has had on me, and was incredibly pleased to receive a letter from him this week. #tellyourheroes

New horizons for Immunology

by Becky Allen

New group leaders bring new skills, new expertise and new perspectives, and 2018 saw three new group leaders join the Institute’s Immunology programme. Professor Adrian Liston, Dr Claudia Ribeiro de Almeida and Dr Sarah Ross talk about their research, their ambitions and what makes the Institute such a special place to work.

They come from VIB in Belgium, Oxford’s Proudfoot lab and the University of Dundee, they focus on different areas of immunology and bring new interests and expertise, but Professor Adrian Liston, Dr Claudia Ribeiro de Almeida and Dr Sarah Ross are all hugely excited to have recently joined the Institute.

Liston, already an established group leader, works on the specialist population of immune cells known as CD4T cells. These cells effectively coordinate and ‘turbo charge’ our immune response. They are also the cells that are targeted by HIV, explaining why the disease causes immune system suppression and illustrating how crucial CD4T cells are to our overall health.

At VIB, Liston specialised in translational immunology, understanding and then developing ways to treat children with rare immune diseases. “These diseases are incredibly severe, but once you understand them mechanistically you can work out ways to treat them,” he explains. “It was very rewarding because these kids that would otherwise often die can go on to lead long, healthy lives once you’ve found out what’s wrong and how to fix it.”

At the Institute, Liston wants to answer three key questions: how the millions of CD4T cells in our bodies communicate and cooperate; how they switch between a ramping up and damping down cell type; and what they do in our tissues. Understanding how these cells modulate our immune system means that they can potentially be used as a tool to fine tune the immune system to help overcome age-related decline.

With its world-leading Immunology programme and cutting-edge facilities the Institute is a great fit for Liston’s ambitions. But what sets the Institute apart is how it nurtures scientific innovation and champions equality and inclusion.

“Great research requires fantastic people who think as differently as possible, which means having an environment that celebrates equality and inclusion. The Institute has a great reputation for this internationally – it’s setting the gold standard for equality and inclusion. You can feel the difference here,” says Liston. “The Institute provides an environment where you’re going to be stimulated and have the chance to explore the limits of your imagination.”

Ribeiro de Almeida and Ross both believe the Institute’s culture will help them build their first research groups. “It’s a very friendly, supportive environment. Everyone is ready to help with time and feedback – they want you to succeed and that’s really special,” says Ross.

Ribeiro de Almeida’s work centres on B lymphocytes and the rare ability they have to rearrange antibody genes by cutting and pasting DNA in order to fight the plethora of pathogens to which we are exposed. “I’m interested in understanding how this mechanism is regulated throughout cell development,” she explains. “It’s a fundamental question, because mistakes in this process can result in leukaemia and lymphoma. To understand these diseases and wider age-related immune dysfunction it’s important to understand how these molecular mechanisms are regulated.”

As a postdoc in Oxford, she worked in a lab that studied gene expression rather than B cells, so she brings a more molecular approach to the programme. She also discovered an RNA-binding protein that plays an important part in B lymphocytes’ cut and paste process, something she’s keen to follow up: “The research I want to do next is to identify which proteins are implicated in this mechanism of gene rearrangement and how they modulate B cell responses.”

Ross specialises in T lymphocytes and the impact that hypoxia – or low levels of oxygen – has on the way they work. Because T cells commonly encounter hypoxic environments, they can adapt to low oxygen environments by changing the proteins they express. While this helps them survive, it can also make them less effective killers of disease cells.

“I want to understand how oxygen regulates T cells from a signalling and gene expression perspective,” she explains. “If we could identify factors that we could target therapeutically to overcome the effects of low oxygen and boost the ability of T cells to perform their protective function, that would be amazing.”

We know that as we age, our immune system becomes less effective and poorer oxygenation is also connected with ageing, so what Ross discovers about hypoxia could have important implications, both for our understanding of the ageing immune system and in making immunotherapies more successful.

The arrival of all three is an exciting opportunity for the Institute, the Immunology programme and its three new group leaders. “It’s amazing – I’m still pinching myself,” Ross concludes. “It’s great to be able to make new plans and work out how to turn them into reality utilising the know-how and the facilities we have access to here. And it’s exciting to be here because my plans cover all three programmes – Immunology, Signalling and Epigenetics – adding my own to all the expertise here makes it hugely exciting.”

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When should I apply for a fellowship?

To develop an academic career in research you need to develop two sides of your CV - one is your publication record and the other is a record of prizes, fellowships and grants. Publications are hard. Years of research and a brutal revision process make accumulating a publication record slow and painful. Prizes, fellowships and grants are, in principle, easier. You write up a proposal and submit. Often you can even submit the same proposal in multiple places. It is very rare that prizes are awarded without you applying for it, so sending out a lot of applications just makes sense.

For poster prizes, departmental awards, travel grants, the equation is quite simple: apply for them. There are a lot of small prizes that are usually under-subscribed, they can earn you a little money and these small prizes build up to greater things. For fellowships, on the other hand, I have started to lean in the other direction. I used to suggest that all post-docs apply for a fellowship - if successful, it is a nice income and a highlight in your CV, and if unsuccessful, well... it is good practice. Now, however, I tend to discourage fellowship applications very early on in the career. Newly graduated PhD students are often very keen to apply for fellowships, and there are so many opportunities that you can easily spend a year applying for one after the other.

The question that you need to ask yourself is whether applying for fellowships is a a good investment of time. A successful fellowship application normally merges a great idea (the science) and a proven record to deliver that idea (most importantly, your publication record). A lot of post-docs make the mistake of applying for fellowships too early, before their publication record is ready to support it. It is easy to think that there is no cost to doing so, but applying for fellowships takes a non-trivial amount of time. As a scientist you always need to weigh up the opportunity cost: time spent on fellowships is time not spent on experiments. There are times when applying for a fellowship is sensible, and other times when you are better off investing all of your energy in experiments (building that publication record for future fellowships). Here are a few factors that you can consider:

Factors that should encourage you to apply for fellowships:

• You are a senior post-doc looking to become independent
• The fellowship allows you to take a key mobility step (eg, Marie Curie to return to Europe)
• You just published a highlight paper
• Your PI says you need a fellowship to stay in the lab (but consider moving labs instead)
• You don't expect your CV to improve in the next year
• You will not be eligible next year

Factors that should discourage you from applying for fellowships:

• Your PI has a grant that covers the full period of your project
• You have a top story cooking (it deserves all your attention!)
• Your publication record is relatively thin, without any highlight papers (but watch out for being excessively self-critical! A neutral faculty member is a useful independent judge)
• You expect your CV to improve in the next year

My suggestion: rather than automatically write a fellowship, because that is what post-docs do, carefully consider the factors above, consult with faculty and then rationally decide where to invest your effort. Make sure that you don't talk yourself out of applying just for reasons of self-confidence, but also don't be afraid to concentrate on the science this year instead of applying, to put yourself in a better position to apply next year.