Top 10 health innovations of 2020
Great to see our recent Cell paper on brain T cells licensing microglia listed as one of the top 10 health innovations of 2020!
Becoming a Scientist
Virus Fighter
Build a virus or fight a pandemic!
Maya's Marvellous Medicine
Battle Robots of the Blood
Just for Kids! All about Coronavirus
Great to see our recent Cell paper on brain T cells licensing microglia listed as one of the top 10 health innovations of 2020!
Anti-vaxxers are out in force with more false claims about the COVID-19 vaccine. I'm mystified about what their endgame is - no vaccines, no masks, no technology, no medicine, cowering in caves like Stone Age humanity?
Anyway, today's false claim is that COVID-19 vaccines can cause heart attacks due to potassium chloride. The truth is, potassium chloride is an essential electrolyte, in every food we eat and every drink we drink. It is recommended that we take in 2000mg of potassium per day, which is about 4000mg of potassium chloride. So how much potassium chloride is in the COVID-19 vaccine? 0.01mg. Yep, that is what the anti-vaxxers want you to be petrified of.
0.01mg is about 1% of the amount of potassium chloride present in a glass of tap water. It is about 50,000 times less than the amount of potassium chloride present in a glass of milk or a banana. It is about the same amount of potassium chloride present in the solitary tear that I wept thinking of those poor anti-vaxxers being given the option to have a life-saving vaccine developed at incredible speed.
The fake excuse anti-vaxxers give for their pseudo-concern is that potassium chloride is used in lethal injections. Yes, at one million times the vaccine dose, and without the balancing sodium that is present in alls foods and vaccines. A small amount of sodium and potassium mixed together in a balanced ratio is good. A vast amount of potassium injected straight into the bloodstream is bad. Pretty simple difference, and I'm not giving anti-vaxxers the benefit of the doubt by assuming they are just ignorant. They are evil, deliberately spreading things they know to be false, resulting in people not taking life-saving medication.
More fact-checking for COVID-19. This time for a claim so false it is down-right criminal.
Claim: The Pfizer COVID-19 vaccine has a strong sequence similarity with syncytin-1, and will cause infertility.
Verdict: False. A complete fabrication. In summary, there is no sequence homology between the Pfizer COVID-19 vaccine and syncytin-1, and there are no associations betwee anti-SARS-CoV-2 antibodies and pregnancy issues. Looking at the history of the people making the claims, their strategy seems to be to throw random mud at any vaccine and hope some of it sticks.
First, on the sequence homology claim. There is essentially no homology between these two proteins. The full protein sequence of both are known. The language of proteins can be considered to be similar to English - there are 20 different amino acids, and each of them is given a letter. In the same way that a paragraph is constructed by 27 letters of the alphabet, a protein is constructed by the 20 "letters" of amino acids. What matters is the order.
Here is the spike protein:
MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPRRARSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCKFDEDDSEPVLKGVKLHYT
Here is human syncytin-1:
MALPYHIFLFTVLLPSFTLTAPPPCRCMTSSSPYQEFLWRMQRPGNIDAPSYRSLSKGTPTFTAHTHMPRNCYHSATLCMHANTHYWTGKMINPSCPGGLGVTVCWTYFTQTGMSDGGGVQDQAREKHVKEVISQLTRVHGTSSPYKGLDLSKLHETLRTHTRLVSLFNTTLTGLHEVSAQNPTNCWICLPLNFRPYVSIPVPEQWNNFSTEINTTSVLVGPLVSNLEITHTSNLTCVKFSNTTYTTNSQCIRWVTPPTQIVCLPSGIFFVCGTSAYRCLNGSSESMCFLSFLVPPMTIYTEQDLYSYVISKPRNKRVPILPFVIGAGVLGALGTGIGGITTSTQFYYKLSQELNGDMERVADSLVTLQDQLNSLAAVVLQNRRALDLLTAERGGTCLFLGEECCYYVNQSGIVTEKVKEIRDRIQRRAEELRNTGPWGLLSQWMPWILPFLGPLAAIILLLLFGPCIFNLLVNFVSSRIEAVKLQMEPKMQSKTKIYRRPLDRPASPRSDVNDIKGTPPEEISAAQPLLRPNSAGSS
They both start with "M", like every protein in mammals, but apart from that do you see any similarity? No? Me either. Or any of the protein homology tools that I tested. The closest you get is a run of 2-3 letters being the same. Claiming homology between the two sequences is worse than claiming the US Constitution and Harry Potter are the same, because they both use words like "at" and "the".
How about the second claim? If anti-spike protein antibodies interfered with fertility, you would expect that COVID-19 patients, who almost all make high titres of anti-spike protein antibodies, would have infertility issues. They don't. Multiple studies show no complications with pregnancy or miscarriage in pregnant COVID-19 patients. This is an extreme case - these individuals have an ongoing serious viral infection as well as having the antibody response - and yet there is clear evidence of maintained fertility.
Today I took part in a COVID-19 vaccine trial (ENSEMBLE2) as a volunteer. It is the Ad26.COV2.S vaccine, an adenovirus-encoded SARS-CoV-2 spike antigen.
Right now, we can use every vaccine we can get. Down the track we can be picky, and use the best ones (if we ever actually find out which are the best! if head-to-head trials aren't done now, they will likely never be done). For now, I'd encourage everyone who is eligible to join a vaccine trial.
As many people possible vaccinated, everyone wearing a mask and eliminate unnecessary contacts. We are so close to beating this virus, every extra death at this stage is an unnecessary trajedy.
A team of immunology experts from Belgium and the UK research organisations have come together to apply their pioneering research methods to put individuals’ COVID-19 response under the microscope. Published today in the journal Clinical and Translational Immunology, their research adds to the developing picture of the immune system response and our understanding of the immunological features associated with the development of severe and life-threatening disease following COVID-19. This understanding is crucial to guide the development of effective healthcare and ‘early-warning’ systems to identify and treat those at risk of a severe response.
One of the most puzzling questions about the global COVID-19 pandemic is why individuals show such a diverse response. Some people don’t show any symptoms, termed ‘silent spreaders’, whereas some COVID-19 patients require intensive care support as their immune response becomes extreme. Age and underlying health conditions are known to increase the risk of a severe response but the underlying reasons for the hyperactive immune response seen in some individuals is unexplained, although likely to be due to many factors contributing together.
To investigate the immune system variations that might explain the spectrum of responses, teams of researchers from the VIB Centre for Brain and Disease Research and KU Leuven in Belgium and the Babraham Institute in the UK worked with members of the CONTAGIOUS consortium to compare the immune system response to COVID-19 in patients showing mild-moderate or severe effects, using healthy individuals as a control group.
Professor Adrian Liston, senior group leader at the Babraham Institute in the UK, explained: “One of our main motivations for undertaking this research was to understand the complexities of the immune system response occurring in COVID-19 and identify what the hallmarks of severe illness are. We believe that the open sharing of data is key to beating this challenge and so established this data set to allow others to probe and analyse the data independently.”
The researchers specifically looked at the presence of T cells – immune cells with a diverse set of functions depending on their sub-type, with ‘cytotoxic’ T cells able to kill virus-infected cells directly, while other ‘helper’ T cell types modulate the action of other immune cells. The researchers used flow cytometry to separate out the cells of interest from the participants’ blood, based on T cell identification markers, cell activation markers and cytokine cell signalling molecules.
Surprisingly, the T cell response in the blood of COVID-19 patients classified as severe showed few differences from the healthy volunteers. This is in contrast to what would usually be seen after a viral infection, such as the ‘flu. However, the researchers identified an increase in T cells producing a suppressor of cell inflammation called interleukin 10 (IL-10). IL-10 production is a hallmark of activated regulatory T cells present in tissues such as the lungs. While rare in healthy individuals, the researchers were able to detect a large increase in the number of these cells in severe COVID-19 patients.
Potentially, monitoring the level of IL-10 could provide a warning light of disease progression, but the researchers state that larger-scale studies are required to confirm these findings.
“We’ve made progress in identifying the differences between a helpful and a harmful immune response in COVID-19 patients. The way forward requires an expanded study, looking at much larger numbers of patients, and also a longitudinal study, following up patients after illness. This work is already underway, and the data will be available within months,” says Professor Stephanie Humblet-Baron, at the KU Leuven in Belgium.
“This is part of an unprecedented push to understand the immunology of COVID-19”, concludes Professor Liston. “Our understanding of the immunology of this infection has progressed faster than for any other virus in human history – and it is making a real difference in treatment. Clinical strategies, such as switching to dexamethasone, have arisen from a better understanding of the immune pathology of the virus, and survival rates are increasing because of it”.
Professor Liston and Professor Humblet-Baron both emphasized the importance of the scientific team that led the study. "This work happened during a period of incredible stress. When much of our laboratory was shut down due to the pandemic, Dr Teresa Prezzemolo and Silke Janssens were in the hospital day-after-day, preparing blood samples that were critical not just for this study but for a whole host of clinical trials on COVID-19 based in Leuven. Julika Neumann and Dr Mathijs Willemsen put their PhD research on hold to run samples, and Dr Carlos Roca and Dr Oliver Burton provided the computational support to turn the data into biological understanding. We are both incredibly proud of the entire team."
Neumann, J., Prezzemolo, T., Vanderbeke, L. & Roca, C.P. et al. Increased IL-10-producing regulatory T cells are characteristic of severe cases of COVID-19. Clinical and Translational Immunology
Part of managing staff and students is to manage their scientific progress. Another aspect is to manage their personal growth and career pathway. Often it is easy to forget the latter, so I make sure that at least once a year I have a formal feedback session on management and careers with everyone in my lab. There are five stages to this, and this year it basically took me two weeks (but this is because I am currently still running two fairly large labs, one in Belgium and one in Cambridge).
Step 1: Anonymous survey of the whole lab. Here I use SurveyMonkey, with a series of questions that allow a quantification of satisfaction in different aspects of lab culture. I focus on questions that measure trust and happiness in the lab, like whether people plan to keep in contact with each other after graduation, how well they feel lab duties are balanced, etc. This is useful to get a bird's eye view of lab culture, which is otherwise biased towards the more vocal lab members. It is important not to get hung up on every negative answer - just because 100% of the lab isn't happy in every aspect doesn't mean you are doing things wrong. Instead it should be more of a comparative indicator. Are people more happy with the lab than the institute or vice versa. After a couple of years it also lets you do longitudinal comparisons - are problems being fixed after identification? Here is the list of questions that I used this year, and the answers of my Cambridge lab:
My interpretation: when people's biggest complaints about about seminars and journal club, then you have a healthy lab. We are also fortunate that this year there are many options for online seminar series of very high quality, so alternatives are available.
In the survey I also include a section allowing free-form answers to certain questions. It is more biased (few people answer them all), but also carries more information. This year those free-form questions were:
How should we run lab meeting?
How should we run journal club?
How could lab duties be better assigned, and are there new duties that need to be added?
Long-term, what new skills should we look at developing?
In our science headed in the right direction?
How much productive time did I lose due to COVID?
What new practices, put in place because of the lockdown, should we keep afterwards?
What extra changes should we make for the upcoming six months, to reduce the impact of partial lockdown?
What extra equipment would be nice to have in the lab?
Any other feedback?
Ideally, these would be addressed in the personal feedback (see below), but it is good to have the option for confidential comments.
Step 2: Individual self-evaluation from each lab member. Here I ask everyone to reflect on their strengths and weaknesses, their achievements and ambitions, things that they could have done differently and things that I could have done differently. I generally ask the same questions every year, although this year I had an extra section on how COVID affected them. I make sure to tell people upfront that this is not an official evaluation, it is a self-reflection piece. This is the form I ask them to fill out. This is a really valuable exercise for several reasons:
1) It gives people a time to reflect on their past year and their following year, to contemplate their future career
2) The questions are designed to focus around problem-solving, rather than blame assigning. What can you do to improve your chance of achieving next year's goal? What I can do to help you achieve this goal? Simply getting people to consider their own agency can be the push that is needed to solve problems
3) It let's me know what their goals are, for your next year and your career. The more information I have on where you are going, the more useful my mentoring will be
4) It let's me see how closely aligned their self-evaluation is to my evaluation of them. The biggest management problems arise from unaligned evaluations of skills. If someone is convinced that they are an excellent communicator and you think they are a poor communicator, then that needs to be resolved. Likewise if someone feels like they are behind in their PhD and you think they are ahead of where you expect them to be, that also needs to be resolved. Which brings me to:
Step 3: My written comments on their self-evaluation. Here I go through their evaluation and put down my comments. Where they list their strengths I highlight the ones that I agree with, and I mention strengths that they forgotten. Where they list their weaknesses I comment on weaknesses that I agree need to be fixed, with a proposed strategy, or I'll explain why I don't think the person is actually weak in that aspect, and perhaps it is more an issue of self-confidence than a real weakness. I'll comment on their key achievements, and mention extras that they may have forgotten. I'll discuss their proposed pathways to improvement, oftening higlighting just one for them to focus on in the next year (trying to do everything is not a great approach). I'll reply to where they ask for help, either promising that they will have it, or explaining why that particular suggestion is not suitable and proposing an alternative. I'll comment on their career plans, whether or not I think they are on the right track to achieve them and how they should go about preparing for the next step. I am always honest - I don't see any value in helping a post-doc deceive themselves that they are on the track to independence if they are not - but this does not need to be cruel. It is more about exploring whether or not they actually want to be on that track, explaining what needs to change for them to move onto it, or explaining the alternative track that they may be moving towards without being aware. I make it a point to be positive (especially with people who have under-estimated themselves, a more common phenotype than over-estimation). I also make it a point to recognise where my failings contributed, to take responsibility for this and to commit to a change in myself. Even if that is as simple as "I should have stepped in earlier", it leads by example in taking responsibility for your actions.
I like to give written feedback, even though I'll have a face-to-face meeting afterwards. It gives me the time to organise my thoughts. It lets me read and re-read to see if I struck the right tone. It means I go through all the points on the document. It also lets my staff read and re-read the comments. Sometimes things become emotional in feedback meetings, and your perception of what is being said is changed by the emotional context. You focus in on negatives and forget the positives.
Step 4: A face-to-face meeting. Here there is a follow-up meeting. Usually I don't go through the document - we've both seen the self-evaluation and my comments. I insist on no science at this meeting, it is all about them, our relationship and their career. Often I'll focus on just one aspect that I think is the most important. The meetings usually last thirty minutes, sometimes out to two hours each. Most common themes:
Junior PhD student, learning what a PhD is. Yes, you are on track. You really are. It is normal that you feel like you are not. Of course you don't know everything you need to know, you are here to learn.
Senior PhD student, looking at their next step. Should I stay for a post-doc? Should I write a fellowship? Should I move to industry? You should make a decision based on interest, not based on fear. If you are more interested in industry, go there. Here is how to start building your industry-entry plan. But don't move to industry because you are scared academia is too tough.
Junior post-doc, scared to ask for help. I know you were on top of your game at the end of your PhD, but that doesn't mean you start from the same place in a new lab on a new topic. Science is constantly learning. You need to communicate. If something isn't working, don't hide it until it works. Talk to me. Failure to talk can make our relationship non-functional, and doesn't help anyone.
Senior post-doc, looking at an independent position. Okay, let's look at the facts. How mobile will you be? What are the options available to you and your family? What are the timelines of applications? How early will you need to send me drafts to have sufficient time to address my feedback? Who can I network you with? What do we need to work on with training sessions?
Expecting parent. Alright, let's be realistic here. It is going to be brutal being a new parent. This was my experience. No, you are not going to be able to get X, Y or Z done while on parental leave. Organise everything and we'll get someone else to cover you - but it is up to you to organise things in advance. Samples, folder structure, design of experiments - they need to be able to access everything. When do you get back? Again, let's be realistic and assume you are functioning at 50% productivity for the year after that - anything extra will be a pleasant surprise. Better to finish one thing than leave ten partially completed. Make sure to establish good equal co-parenting from day one!
Super-scientist with crippling self-doubt. You are great, you really are. I know that it is hard to see your success in yourself. I spend half my time in a state of career anxiety, even after a great paper comes out. Sometimes it is just hard to trust your own judgement, and science constantly focuses in on the negatives. If you can't trust your judgement at the moment, trust mine. You're great.
Step 5. Follow-up! Meetings need actions and behavioural changes to follow. Follow-up with them, make sure that they are putting their actions into place. Follow-up on yourself, check that you are meeting your own commitments. Check-in with them as to whether their goals are changing, especially after big events (that confidence boost from a publication might make them reconsider academia, that tech-transfer conference might have swayed them towards industry). Your relationship with your lab is a work in progress, not a tick-box once a year.
Congratulations to Julika Neumann for winning the 8th Golden Pipette at the 2020 virtual lab retreat.
Brutally tough competition this year - the quality of science is just constantly rising year after year. I was really tempted by Orian's UMAP analysis (it looks like an elephant!):
But for that single piece of data that just speaks for itself, it is hard to go past this crystal structure of a point mutation found in a novel primary immunodeficiency gene:
Well done Julika!
Julika receiving the Golden Pipette from past winner Lidia, in our virtual happy hour
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:
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.
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!