Lab retreat 2020 edition

Our lab retreat is a real highlight of the lab, with the Leuven and Cambridge teams getting together to share ideas and progress, brainstorm and socialise. We usually have a couple of retreats a year. Unfortunately our first was cancelled in 2020 by the lockdown, and we decided to make the second one virtual.

Having spent many, many hours on zoom calls over the past six months, I was quite worried about three solid days of a virtual zoom meeting. Fortunately it was a great success! Excellent science (of course) and the level of interaction was as good as an in-person retreat. I don't think it can ever replace in-person meetings, since the success builds on the already-existing personal connections, but perhaps a virtual retreat will substitute for every second retreat going forward?

Secret tips for a zoom retreat:

• Planning in advance. We sent out a spreadsheet with all the links, talk times and titles, discussion blocks, social activities, etc. There was a lot to plan, so I delegated tasks to lots of people, but that still means a lot of follow-up to make sure people have actually done their bit and communicated it. The investment in advance is worth it though! We were lucky to have Dr Loriana Mascali to coordinate much of the retreat, and there was great investment by many lab members on different sections.
• Have a dynamic schedule. Lots of small talks with breaks is easier to handle. For several people we broke up their talk into several subtalks to make sure that all talks were between 10 and 30 minutes. We also arranged to be zoom-bombed by Daisy the goat, to break up the rhythm. Enough discussion time needs to be added, otherwise you'll end up consuming the break time.

• Stick to the schedule as much as possible. Talks that start to really drag on are often those where there are big problems - there is only so long it is helpful to hammer home those points. Build some flexibility into the schedule (so you can keep positive discussions going even if they go over time), but don't let it derail the entire program. Having breakslides is also useful, so that people can always see when the talks resume by looking at the screen, rather than needing to check the program and try to remember if they were five minutes behind or not.
• Actively try to stimulate discussion and interaction. It does not happen organically on zoom, so you need to promote it. I used secret "cheerleaders and shade-throwers". A cheerleader needs to make a positive comment on a talk, while a shade-thrower needs to make a critical comment. They then pass the duty off (in secret) to another person. The net effect is that people get used to making comments, and you have a 2:1 ratio of positive:critical comments. It makes for a lot of conversation and use of the zoom chat. Eventually everyone catches on, but the habit is already established by then! We also used polls, with pre-defined multiple choice questions on each talk. If you see someone not participating, a private chat message can encourage them to engage once, after which they are more likely to engage again.

• Social activities. We had lab bingo running each day (with custom words), which people really got into. Zoom werewolf was a huge success. Virtual escape room was fantastic, which for us was custom made "escape from the lab cold room", but there are plenty of paid options available. Break-out rooms for social interaction are good, but should be broken into smaller groups to get conversation going (6-8 people are good).

• External guests. We invited several potential post-docs / students and long-term collaborators to join. I made it clear up front that they weren't expected for the full three days, and they had the program so that they could jump in for the sessions that interested them the most. A nice way to get expert feedback from people who are not the same old good. 

The ingredients for a successful lab

Trying to reflect on what constitutes a successful lab, these are the 11 ingredients that I work towards bringing together:

A diverse set of experienced staff. Junior staff come in with a passion and enthusiasm that is second to none. However they also are all being trained in the same environment. By contrast post-docs and senior technicians have been trained in different environments, so they bring with them novel experiences. Having a mixture of staff at different levels and with different educational and life backgrounds optimises the chance that the key idea or skill set will be available. Having at least a few staff members with a long-term perspective in the lab is one of the most potent advantages a lab can have - it means the institutional knowledge is shared between multiple staff, and not all residing in the PI.

A dynamic and supportive lab culture. A successful lab is one with high morale, where people see that effort leads to results. The lab culture should be interactive and supportive. A community feeling, where everyone will jump in to get a project over the line, is critical. A place where everyone feels open to speak up and can live with being criticised is a place where experimental design can be optimised before hitting the bench. A healthy lab is one where the PI is only one voice, and there is just as much peer-to-peer flow of information and ideas.

Output spread across the lab. If the output is concentrated in a handful of people it is suggestive of wasted potential, and puts the lab at risk when the productive people move on. Ideally, every researcher should be getting a first author paper every 3 years.

A healthy portfolio of funding. Ideally this includes a mixture of small and large grants, with a long horizon. The reason why I specify a portfolio is that having all of your funding via one large grant creates a difficult problem when that grant is ending.

A pipeline of research projects. A strong research pipeline includes having high potential projects in the incubation stage, development stage, submission/review stage and published. It can be difficult to manage a pipeline, because you need to switch gears between different projects that need different styles of management and cost/benefit analysis. However the advantage is that there is always something cooking, so it doesn't create the problem of synchronised publication and then a long research gap while you start from scratch.

Balance of diversity in research projects. Focus on a topic gives synergy between projects at both the technical and intellectual level. Diversity of topics brings opportunity and reduces risk. Finding the sweet-spot between focus and diversity is difficult but brings advantages.

Creativity and innovation. A successful lab does research that isn't being done somewhere else. This means creativity and innovation, rather than doing the next obvious thing a little faster than the competition. This can come in different forms: developing new tools, to answer questions other people can't, coming up with creative approaches that other groups haven't thought of, or simply asking different questions.

A reserve of soft money. "Soft money", not tied to a project or time-limited, is precious and difficult to obtain. The advantages are enormous though, allowing investments that later lead to grants. A key advantage is that a reserve of soft money can be used to buffer long-term senior staff between grants. Knowing that you can fund senior staff even if there is a year gap between grants helps you keep the most essentially staff in the lab - even if you never need to actually use the reserve

Quality collaborations. A balance between working in isolation and acting as an academic CRO for other labs. Quality collaborations are usually reflected through bidirectional help, where they contribute to your work and you contribute to their work.

Access to high-end equipment and facilities. High level science is increasingly dependent on high level equipment and specialist staff, beyond what can be built and maintained in a single lab.

Supportive institutional and administrative staff. All the ingredients can be there, but if the departmental head is against you or admin work against you, the lab can be crippled. A group leader spending >50% of their time on admin, or research staff spending >25% of their time on admin, is a warning sign.

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!

The CrispR revolution

Emmanuelle Charpentier and Jennifer Doudna have just won the Nobel Prize for Chemistry. They have been my picks for the prize for years now. Nobel Prizes are often awarded decades after the fact, but CrispR has been such an obvious winner that it is a surprise it took until 2020 to be awarded. (Largely, I guess, due to the politics of several competing claims and patents, that have been going through the courts). 

This Noble is a well-deserved recognition of one of the seminal breakthroughs in biology of the last several decades. The award recognises elegant basic biological experiments that identified a novel immune mechanism that bacteria use to fight off viruses. The key insight is that the chemistry of this system allowed simple modifications to rewire this bacterial system into a tool to edit the genome of essentially any living being. A striking example of blue-skies research on basic science having an incredible translational effect. The CrispR system ranks up there with identifying the structure of DNA or the sequencing of the human genome - indeed, for the first time it allows us to really use the information gained by these earlier revolutions. CrispR tools are used daily across the globe to create new vaccines, generate gene therapy, design bacteria to help industrial processes. Essentially, the discovery of CrispR as a genome-modification tool has put biology on steroids - dramatically accelerating the pace of both basic research and translational applications

Fact-checking COVID-19 claims

From a recent interview with a fact-checking journalist:

Claim: Alcohol-based hand sanitiser shouldn't be used day after day as it breaks down the first immune barrier of the body: the lipid bacteria of the skin.

Verdict: Misleading. Alcohol-based gels do reduce the number of skin-resident bacteria and can start to cause some damage to the skin with prolonged use, in some individuals. However, the skin barrier is irrelevant to COVID-19, and alcohol-based gels also eliminate viruses from the skin, preventing transmission to surfaces and your face. Overall there is a clear benefit to use frequent hand-washing, and the negatives can be countered with moisturising.

Claim: We can strengthen our immune system in weeks or even days (for young people), which would mean that if one does contract COVID-19, it's more likely going to be a mild case which does not require hospitalisation.

Verdict: False. First of all, it is misleading to talk about "strengthening" the immune system. The immune system could be considered more like taste. You can increase how spicy food is, or increase how sweet food is - both are "strengthening" the taste but mean different things. Different "flavours" of the immune response are optimal in different circumstances, so there is no such thing as a generic increase in how strong the immune system is. It is also completely unclear as to whether we actually want a "stronger" immune response in COVID-19 - there is good evidence that an excessive immune response of one particular "flavour" is causing the immune pathology. We want to train the immune response in a particular direction (e.g. through vaccines) not generically increase its power (even if that was possible, which it isn't).

Claim: A well functioning immune system is dependent on the quality of our intestinal flora. This is why we should avoid eating refined "industrial" food.

Verdict: Half true. There is an interaction between the gut bacteria and the immune system, and this is modified by the food we eat. It is not very well understood, and it is likely too early to say whether the net effect of the consequences is generally good or generally bad. It is certainly too early to say whether it makes a positive or negative effect in the case of COVID-19. As general advice, eating fresh and unprocessed foods, high in vegetables and low is red meat is good health advice, regardless of what it does to the immune system.

Claim: Fasting strengthens the immune system in only 3 days.

Verdict: False. Fasting modifies the immune system slightly, which could be advantageous in some circumstances and detrimental in others. It is a minor effect though, and certainly it would not be advised that someone with symptomatic COVID-19 undergoes extensive fasting. The body needs resources to fight an infection.

Claim: Herbal supplements such as echinacea and elderberry strengthen the immune system in a matter of weeks.

Verdict: False. There are active compounds in all plants, which can modify aspects of the immune system if given in high enough doses in a dish. That does not mean that eating a few pills does anything at all. It is very important for people to understand that supplements and medicines are regulated completely differently. "Supplements" are allowed to make essentially any claim, without any evidence, as long as that claim is vague. This is why you get garbage claims about "immune boosting": they are vague enough that they are legally allowed to be made without evidence. Actual medicines, on the other hand, can only make extremely specific claims that are backed up by evidence. All claims about herbal supplements should essentially be treated as advertising material. 

Claim: Vitamins and minerals strengthen the immune system.

Verdict: Misleading. Vitamins and minerals are different from other supplements. They are needed by the body in extremely low quantities, and if they are absent then health problems arise. For people who are actually deficient, taking vitamins and minerals will improve health, including the immune system. However, almost no one in the developed world is actually deficient, and certainly having a balanced diet of fresh food will give you more than enough of every known vitamin and mineral. Unless you have an exceptionally limited diet, taking these tablets doesn't do anything.  

Claim: Fear is a powerful immunodepressant.

Verdict: Half-true. Anxiety can modify the immune system, and can give poorer health outcomes during some types of infection. The effect is weak to moderate, but it is measurable. This should not be used as an excuse not to spread awareness of the COVID-19 pandemic, however: some degree of anxiety is rational and protective, where it supports valid infection-avoidance behaviours (e.g., hand-washing, wearing a mask, avoiding crowded areas).

Claim: Practicing yoga strengthens the immune system.

Verdict: Misleading. There is nothing special about yoga. There are, however, weak to moderate beneficial effects of exercise and the alleviation of anxiety on infection outcomes. For some people, they may get this through yoga. Others may get it through gardening, or a daily run, or the ritual of a cup of tea. We should look after our mental health, which means cultivating habits that make us happy. The idea that one particular solution like yoga or mediation has any special properties beyond this is completely unsupported. Keep it up if you enjoy it, but it doesn't replace medicine and won't work for every person.

Unpopular opinion: the scientific publication system is not the problem

Scientific publishing is undergoing radical change. Nothing surprising there, scientific publishing has been constantly evolving and constantly improving. Innovation and change are needed to improve, although not all innovations end up being useful. I'm on record for saying that the DORA approach, for example, is ideologically well meaning, but so little consideration has been made of the practicalities that the implementation is damaging. Open-access is another example: an excellent ambition, however the pay-to-publish model used for implementation turbo-charged the fake journal industry. I am glad that we have advocates pushing on various reforms to publishing: pre-print, open-access, retractions, innovations in accreditation, pre-registration, replication journals, trials in blind reviewing, publishing reviews, etc. The advocates do seem, to me, to have far too much belief that their particular reform is critical and often turn a blind eye to the potential downsides. That is also okay: the system needs both passionate advocates and dubious skeptics in order to push changes, throw out the ones that don't work and tweak the ones that do work in order to get the best cost/benefit ratio of implementation. Fundamentally, though, the publication system is not broken. Oh, it is certainly flawed and improvements are needed and welcomed. But even if every flaw was fixed (which is probably impossible: some ambitions in publishing are at heart mutually contradictory) I don't think it will have the huge benefits that many advocates assume. Because at the heart of it, the problem is not the publication system, but the other systems that publishing flows into. Let's take two examples:

• Careers. Probably the main reason why flaws in the publishing system drive so much angst is that scientific publication is the main criteria used in awarding positions and grants. So issues with prestige journals, impact factors and so forth have real implications that damage people's lives and destroy careers. DORA is the ambition to not do that, without the solution of an alternative. Perhaps one day we will find a better system (I happen to believe it lies in improving metrics, and valuing a basket of different metrics for different roles, not in pretending metrics don't exist). But even a perfect system (again, probably impossible) won't fix the issue in career anxiety. Because in the end the issue is that the scientific career structure is broken: it is under-funded, built based on short-term perspectives, and operates on the pressure-cooker approach to milking productivity out of people until they break. From a broader perspective, the scientific career structure is not operating in a vacuum - it is part of a capitalist economy which again fuels these anxieties. Why are people so worried about losing their place in the academic pipeline? Because in our economy changing careers is really, really scary. Fixing publishing doesn't actually fix any of those downstream issues.

Dieet met veel suiker verhoogt risico op pancreaskanker

Knack

Suikerrijke voeding veroorzaakt de ontwikkeling van alvleesklierkanker en verhoogt de kans op een dodelijke afloop. Tot die bevinding zijn onderzoekers van het Vlaams Instituut voor Biotechnologie (VIB) en de KU Leuven gekomen.

Een suikerrijk dieet verhoogt niet alleen de kans op het ontwikkelen van pancreaskanker. Het stimuleert ook de agressieve groei van tumoren. Tot die conclusie komen onderzoekers van VIB-KU Leuven en collega's van het Babraham Institute van de Britse universiteit Cambridge.

De resultaten zijn gepubliceerd in het tijdschrift Cell Reports.

Alvleesklierkanker is een zeldzame maar dodelijke vorm van kanker door late detectie en een slecht begrip van risicofactoren. Bekende risicofactoren zijn obesitas, voeding en diabetes type 2, maar door de lage incidentie en de onderlinge samenhang is hun individuele bijdrage moeilijk in te schatten.

De onderzoekers voltooiden een uitgebreid project met experimenteel werk bij muizen en menselijke gegevens. Bij de dieren werd de progressie van pancreaskanker beïnvloed door voedingssuiker, met een snellere tumorgroei en verhoogde dodelijkheid.

Het effect bij mensen blijkt hetzelfde. Bij 500 deelnemers aan de studie onderzochten de onderzoekers de interactie tussen genen en voeding en ontdekten dat hoge niveaus van voedingssuiker het risico op alvleesklierkanker verhoogden. 'We hebben jarenlang gekeken naar verschillende voedings- en genetische veranderingen en niets komt in de buurt van de nadelige gevolgen van een dieet met veel suiker', zegt James Dooley, senior wetenschapper bij het Babraham Institute.

Plantaardige voeding met een equivalent van een avocado per dag vermindert het risico op pancreaskanker met tien procent.

Today in Cell

Not a bad day for the VIB Brain and Disease department...

  

New role for white blood cells in the developing brain

Whether white blood cells can be found in the brain has been controversial, and what they might be doing used to be complete mystery. In a seminal study published in Cell, an international team of scientists led by Prof. Adrian Liston (VIB-KU Leuven, Belgium & Babraham Institute, UK) describe a population of specialized brain-resident immune cells discovered in the mouse and human brain, and show that the presence of white blood cells is essential for normal brain development in mice.

Like a highly fortified headquarters, our brain enjoys special protection from what is circulating in the rest of our body through the blood-brain barrier. This highly selective border makes sure that passage from the blood to the brain is tightly regulated.

The blood-brain barrier also separates the brain from our body’s immune system, which is why it has its own resident immune cells, called microglia, which trigger inflammation and tissue repair. Microglia arrive in the brain during embryonic development, and later on, the population becomes self-renewing.

Yet, white blood cells—which are part of our immune system—have been found to play a role in different brain diseases, including multiple sclerosis, Alzheimer’s and Parkinson’s disease or stroke. Whether or not white blood cells can be found in healthy brains as well, and what they might be doing there, has been subject of intense debate. An interdisciplinary team of scientists led by Prof. Adrian Liston (VIB-KU Leuven, Babraham Institute) set out to find the answers.

White blood cells in the brain

"A misconception about white blood cells comes from their name,” explains Dr. Oliver Burton (Babraham Institute). “These 'immune cells' are not just present in the blood. They are constantly circulating around our body and enter all of our organs, including—as it turns out—the brain. We are only just starting to discover what white blood cells do when they leave the blood. This research indicates that they act as a go-between, transferring information from the rest of the body to the brain environment"

The team quantified and characterized a small but distinct population of brain-resident T helper cells present in mouse and human brain tissue. T cells are a specific type of white blood cells specialized for scanning cell surfaces for evidence of infection and triggering an appropriate immune response. New technologies allowed the researchers to study the cells in great detail, including the processes by which circulating T cells entered the brain and began to develop the features of brain-resident T cells.

Dr. Carlos Roca (Babraham Institute): “Science is becoming increasingly multidisciplinary. Here, we didn't just bring in expertise from immunology, neuroscience and microbiology, but also from computer science and applied mathematics. New approaches for data analysis allow us to reach a much deeper level of understanding of the biology of the white blood cells we found in the brain.”

An evolutionary role

When T helper cells are absent from the brain, the scientists found that the resident immune cells – microglia – in the mouse brain remained suspended between a fetal and adult developmental state. Observationally, mice lacking brain T cells showed multiple changes in their behavior. The analysis points to an important role for brain-resident T cells in brain development. If T cells participate in normal brain development in mice, could the same be true in humans?

“In mice, the wave of entry of immune cells at birth triggers a switch in brain development,” says Liston. “Humans have a much longer gestation than mice though, and we don't know about the timing of immune cell entry into the brain. Does this occur before birth? Is it delayed until after birth? Did a change in timing of entry contribute to the evolution of enhanced cognitive capacity in humans?”

The findings open up a whole new range of questions about how the brain and our immune system interact. "It has been really exciting to work on this project. We are learning so much about how our immune system can alter our brain, and how our brain modifies our immune system. The two are far more interconnected than we previously thought," says Dr. Emanuela Pasciuto (VIB-KU Leuven).

The study also brings in a connection with the gut microbiome, says Liston: “There are now multiple links between the bacteria in our gut and different neurological conditions, but without any convincing explanations for what connects them. We show that white blood cells are modified by gut bacteria, and then take that information with them into the brain. This could be the route by which our gut microbiome influences the brain.” 

Taken together, the results contribute towards the increasing recognition of the role of immune cells in the brain and shed new light on its involvement in a range of neurological diseases.

Check out the full article here

Witte bloedcellen ook belangrijk voor ons brein

Witte bloedcellen maken deel uit van ons immuunsysteem dat ons tegen ziektes beschermt.  Of ze ook in de hersenen terug te vinden zijn, en wat ze daar dan zouden doen bleef tot nog toe een raadsel. Een internationaal team van wetenschappers onder leiding van professor Adrian Liston (VIB-KU Leuven, België en Babraham Institute, VK) toont nu aan dat witte bloedcellen wel degelijk voorkomen in de hersenen van zowel muizen als mensen, en dat hun aanwezigheid essentieel is voor normale hersenontwikkeling. De resultaten verschijnen deze week in het prestigieuze vakblad Cell.

Onze hersenen worden als een versterkte burcht ommuurd door de bloed-hersenbarrière. Die moet vermijden dat stoffen die in onze bloedbaan circuleren zomaar in onze hersenen terechtkomen. Via de bloed-hersenbarrière worden onder strikte controle enkel welbepaalde stoffen uitgewisseld.

De bloed-hersenbarrière schermt de hersenen ook af van ons immuunsysteem, dat de rest van ons lichaam patrouilleert om bijvoorbeeld bacteriële of virale indringers op te sporen en uit te schakelen. Precies daarom heeft het brein z’n eigen immuuncellen: microglia.

Toch blijken witte bloedcellen ook een rol te spelen bij verschillende hersenaandoeningen. Denk maar aan MS, alzheimer, parkinson of een beroerte. Hierbij gaat het wel telkens om ziek of ‘beschadigd’ hersenweefsel, waar mogelijk ook de bloed-hersenbarrière is aangetast. De vraag bleef dus of – en waarom – witte bloedcellen nu werkelijk aanwezig zijn in hersenen die normaal en gezond zijn.

Witte bloedcellen in de hersenen

Een interdisciplinair team van wetenschappers onder leiding van prof. Adrian Liston (VIB-KU Leuven, Babraham Institute) heeft nu een kleine maar belangrijke groep van T-helpercellen ontdekt in hersenweefsel afkomstig van muizen en van mensen. T-helpercellen zijn een specifiek type witte bloedcellen, gespecialiseerd in het scannen van celoppervlakken op aanwijzingen van infectie en in het op gang trekken van een aangepaste immuunreactie. Aan de hand van de laatste technologie konden de wetenschappers de T-helpercellen tot in detail bestuderen, inclusief hoe en wanneer ze in de hersenen terecht komen.

Dr. Emanuela Pasciuto (VIB-KU Leuven), postdoctoraal onderzoeker in het team van Liston benadrukt het belang van interdisciplinair onderzoek: “Om de rol van witte bloedcellen in het brein in kaart te brengen hebben we niet alleen expertise van immunologie, neurowetenschappen en microbiologie bij elkaar gebracht, maar ook van informatica en toegepaste wiskunde. Nieuwe benaderingen voor data-analyse stellen ons in staat om een ​​veel dieper begrip te krijgen van de biologie van de witte bloedcellen die we in de hersenen hebben gevonden.”

Een evolutionaire rol

De onderzoekers stelden vast dat in muizenhersenen zonder T-helpercellen de ontwikkeling van de typische immuuncellen van het brein (de microglia) bleef hangen ergens tussen een foetale en volwassen ontwikkelingsstatus. De muizen zonder T-helpercellen in de hersenen vertoonden bovendien verschillende gedragsafwijkingen, wat wijst op een belangrijke rol voor de T-helpercellen bij de normale hersenontwikkeling. En als dat geldt voor muizen, zou hetzelfde dan ook waar zijn voor mensen?

“We zien dat de toestroom van immuuncellen in de hersenen bij de geboorte van muizen leidt tot een omslag in het ontwikkelingsproces,” zegt Liston. “Maar de zwangerschap bij mensen is veel langer dan bij muizen, en we weten niet wanneer de immuuncellen dan toekomen in het menselijk brein. Gebeurt het nog vóór de geboorte? Is het uitgesteld tot na de geboorte? Kan een verandering in de timing bijgedragen hebben aan de evolutie van de uitzonderlijke hersencapaciteit van mensen?”

De bevindingen openen een heel nieuw gamma aan vragen over de wisselwerking tussen ons brein en ons immuunsysteem. “We leren nog elke dag bij over hoe ons immuunsysteem ons brein kan beïnvloeden en vice versa. De twee zijn veel meer met elkaar verbonden dan we eerder dachten,” zegt Pasciuto.

Darmen en hersenen

De studie legt ook nieuwe verbanden tussen ons brein en onze darmflora, aldus Liston: “Heel wat neurologische aandoeningen worden in verband gebracht met bacteriën in onze darmen, maar zonder overtuigende verklaringen voor die connectie. Onze resultaten laten zien dat darmbacteriën witte bloedcellen kunnen beïnvloeden, die deze ‘informatie’ vervolgens mee nemen naar de hersenen. Dit zou de manier kunnen zijn waarop onze darmflora onze hersenen beïnvloeden. ”

De nieuwe resultaten dragen enorm bij tot de groeiende kennis over de rol van immuuncellen in de hersenen, zowel tijdens de normale ontwikkeling als bij verschillende ziekteprocessen.