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

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

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

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

read the interview with me here

 

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

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

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

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

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

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

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

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

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

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

Leuven teams are the forefront of the project

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

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

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

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

IL-2 cytokine networks

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

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

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

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

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

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!

Fact-checking COVID-19 vaccine claims

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.

Fact-checking COVID-19 claims

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.

COVID-19 vaccine trial

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.

Dissecting the immune characteristics of severe COVID-19 responses

• Researchers have analysed immune cell types and numbers from the blood of healthy volunteers, COVID-19 patients experiencing mild-to-moderate effects and patients classified as severe to understand whether particular characteristics of their immune system response can identify treatment targets or indicate disease severity.
• After comparing the T cell immune response, the researchers noted the surprising absence of a strong anti-viral response in the blood of COVID-19 patients.
• The study identified an elevated presence of anti-inflammatory-producing regulatory T cells in the severely affected patients. If confirmed by larger studies, this could be used as a marker for identifying worsening cases and could provide an insight into the mechanism of disease pathology.

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

My career feedback strategy

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.

The 2020 Golden Pipette

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