Some sporadic insights into academia.
Science is Fascinating.
Scientists are slightly peculiar.
Here are the views of one of them.

Friday, 5 January 2018

Role of airway glucose in bacterial infections in patients with chronic obstructive pulmonary disease

Role of airway glucose in bacterial infections in patients with chronic obstructive pulmonary disease:



Chronic Obstructive Pulmonary Disease (COPD) describes a
group of lung conditions that make it hard to breath. The major cause of COPD is
smoking. Nearly 1.2 million people in the UK suffer with COPD, costing the NHS
more than £800 million a year. Bacterial lung infections are particularly common
in COPD patients. There are a number of reasons that COPD patients are more
susceptible to infection but most research has focussed on failures of the
immune system. We propose an alternative mechanism in our latest paper in the
Journal of Allergy and Clinical Immunology (JACI).
Bacteria, like all living things, need food to grow. The
bacteria that infect us are no exception to this and their food source is us!
The airways are surprisingly rich in nutrients for bacterial growth, some of
this comes from the food we eat (micro-inhalation) and some leaks out from the
blood or cells lining the airways. In healthy lungs, glucose is actively pumped
out of the lungs maintaining it at a low level, but in damaged lungs the flow
of sugar into the lungs exceeds the amount of sugar that can be pumped back out.
Using model systems we have linked this increased lung glucose to increasedlung infection. We think that this works a little like
leaving a jam jar open – bacteria can colonise and grow on the available sugar.

We have now extended these results to patients with COPD. We
measured glucose in samples from COPD patients and found that airway glucose was
higher compared to individuals without COPD. Moreover when COPD patients had an
acute viral infection of the lungs (called an exacerbation) the glucose
concentrations were even higher, probably because the virus further damages the
lung. There was also a direct relationship between the amount of glucose and
the amount of bacteria in the COPD patient samples. We think that
mechanistically, the glucose is elevated because of lung inflammation –
essentially COPD lungs are more leaky, the glucose moves from the blood into
the airways with an impact on bacterial growth.

Why is this
important?


Antibiotics are commonly used to treat infections in COPD,
contributing to the rise in antibiotic resistance. Antibiotic resistant
bacteria (bacteria that are not killed by antibiotics) are a crisis in global
health. If antibiotics stop working, as well as an increase in the severity of
infections that are treatable, much of the medical advances of the last 50
years including surgery and transplants also become ineffective. We therefore
need new ways of killing bacteria. Demonstrating that bacteria are need the
sugar in the airways to grow opens up a new line of attack, cut off the
bacteria’s source of sugar. Potentially this would prevent bacterial infections
in the first place, circumventing the need for antibiotics.

Self-Amplifying RNA Vaccines Give Equivalent Protection against Influenza to mRNA Vaccines but at Much Lower Doses

Self-Amplifying RNA Vaccines Give Equivalent Protection against Influenza to mRNA Vaccines but at Much Lower Doses



Make your own vaccine
With pandemic infections we are always behind the curve,
particularly when it comes to developing vaccines. Vaccines work by inducing a
protective immune memory to an infectious agent so you have to know what the
infectious agent is and which part of the infectious agent the body is going to
recognise to make an effective vaccine. Having identified that, you then have
to make the vaccine, test the vaccine and ship it to the sites where it is
needed in order to give it to people before they are exposed to the infection.
This all takes time.

Manufacture = time
A particularly time consuming hurdle is vaccine manufacture.
This is because most vaccines that we use are protein based, which can be
difficult (and expensive) to manufacture. There are however alternatives. One
approach is to utilise our understanding of how proteins are encoded in our
cells. The source information for proteins comes from genes (encoded in DNA
molecules), this genetic material is copied into an intermediary messenger
molecule called ribonucleic acid (RNA). Remarkably, if you inject either DNA or
RNA into a muscle, that muscle starts making the protein encoded in the DNA.
Even more amazingly, your immune system can then recognise the protein that is
made in your muscle cells and develop a protective response, in the same way
that it would to an injected vaccine.
RNA vaccines
The injection of RNA in particular, seems to be very
effective at triggering an immune response. In our recently published
paper
, we looked at ways to improve how these RNA vaccines work. We compared
two different approaches, the first approach is to make synthetic RNA molecules
that look exactly like the messenger RNA (mRNA) your body makes when it is
making a protein. The second approach is to adapt a trick from a family of
viruses called the alpha viruses, which use the machinery of the cell to make
copies of themselves. We can insert vaccine genes into a safe version of the
alphavirus, which when injected makes multiple copies of the vaccine in the cells
it has been injected into. We call these vaccines self-amplifying as they are
able make more copies of themselves after they are injected.

We compared the two RNA approaches to see which one would
make the best influenza vaccine. Both the mRNA and the self-amplifying RNA
based vaccines protected against influenza virus infection, but strikingly the self-amplifying
vaccines gave the same protection when 60 times less RNA was used. This dose
sparing could potentially be really important in the face of an epidemic where
many people need to be vaccinated in a short time period. We also show that the
vaccine was able to protect after a single dose and it is possible to combine
multiple strains of influenza virus in the same vaccine and protect against all
of them.



We think RNA vaccines show great promise for the future and
this study gives us confidence to move forwards into human studies. 

Wednesday, 4 October 2017

His Job, Her Job: Our Kids



Dr John Tregoning (JT) and Dr Charlotte Tregoning (CT) discuss roadblocks and solutions to equality in childcare. 


We have as a couple, tried and sometimes succeeded but most often failed to share parenting fairly. Drawing from our own experience and a very shallow skim read of how to books, here are what we consider to be some of the major problems to equality at home as two working parents and some possible solutions. This is not to say every parent should go back to work; do what is best for your own family, but remember to be honest with yourself about what you really want and include yourself in the “what is best for my family” calculation.

What society wants
Since the introduction of split parental leave in the UK in 2015, only 1% of fathers have taken it (based on 2015/16 figures). Why is this? Societal expectations are the major barrier to equality in childcare (in 2014 – 33% of people thought mums should stay at home compared to essentially 0% who thought dads should stay home: the flipside 73% thought dads should work full time and 28% thought mums should work full time – but only after the kids go to school). Going against the societal norm is tricky and requires reserves of energy, time and self-belief that you are doing the right thing. When the right thing is also difficult and financially unrewarding these reserves can be depleted, eroding your will.
JT: ‘Ooh, hairy knees, we don’t see them often’, thus began, and ended my time as a stay at home Dad. I was at baby-rhyme-time at the local library, failing to sing along to any of the songs. The librarian looked scornfully at me, made passing reference to my aforementioned knees and then ignored me: I in turn never went back. But societal pressures are only part of it. Staying at home with a small child sucks. It is both boring and difficult, with the attendant loss of identity from Dr Tregoning to Jamie’s Daddy. I did one whole week on my own and even with considerable grandparental support that was frankly enough. I was glad when Monday morning came around to be back in my lab.
CT: It took me till my son’s 9th birthday to openly admit my struggle with societal expectations for me, as the mother, to be the main care-giver. I had always given the reason that due to financial pressures I ‘had’ to go back to work. What I can admit now, but couldn’t when I first had children, is that I always wanted to go back to work. It was easier and less guilt inducing to say that I ‘had to’ rather than I ‘chose to’ – even to myself! That it was my choice has not made the endless juggling act easier, and has sometimes made reaching out for help more difficult.

It’s the economy, stupid
The average age in the UK to have children is 29. Often at the point of conception, fathers and mothers are on equal salary and have equal status. But the early 30’s is a time of logarithmic career acceleration; within the timespan of the maternity leave, major promotions, partnerships and pay rises can occur, which can make the childcare vs income maths skewed towards the parent not on leave (most of the time the father). This can be exacerbated by the arrival of a second child, essentially putting the stay at home partner back by 3 or more years (including the time it takes to adjust from work to stay at home back to work again). Taken as a single data point it makes sense if parent A is earning more than parent B, then parent B should stay home. But it needs to be considered over life time earnings.
CT: In her book, Lean in, Cheryl Sandberg describes childcare costs in the same light as university fees, an investment in future earnings rather than being viewed as a one off cost and in the long run women who return to work earn more than those who take longer breaks. We invested in childcare so that when the children were older I still had a career. 9 years and 2 children later, I have not only caught up with my husband financially but have actually overtaken him. You don’t need 15 years of academic and pharmaceutical training to mush up vegetables and then watch the same vegetable mush being thrown across the room. But as a professional the skills, networks and kudos you have spent those years developing are easily lost.
JT: This year, for the first time in our working lives, my salary is less than Charlie’s. People have asked whether it makes me feel emasculated and unempowered. The truth is that it has been liberating. I have colleagues who are the sole bread winner, exponentially increasing the pressure of failure at work. I on the other hand have a fall-back position, if it my job collapses, the mortgage will still be paid and food will still be on the table. This has given me creative freedom, and actually made me more productive.

Bring balance to the force
So what can be done?
1)      Stop maternal gatekeeping. CT: Allow dad to do things his way - let him be in charge and organise the day – even if it distorts the whole schedule that you have spent weeks carefully putting in place. It is frustrating, annoying and I have had to walk out of the room when he has got cross after our 8 month old rejected food that I would not eat myself (pasta with bisto – a classic). Even if it goes against social norms of the mother being the one in charge or child related matters, shared ownership and decision making in childcare empowers both partners to do more childcare. JT: An analogy – I don’t like doing the dishes, getting told I am doing it wrong does not encourage me to do it better next time, it induces the phrase ‘well you *** do it then’. The same applies to childcare, there is basically no right way to look after kids, so if I have to be in charge, it will be my way!
2)      CT: Expose your husband to the ‘fun’ of full time parenting with a baby for a sustained period. Leave the baby with your husband for a week and then he will hopefully really ‘get’ what it is that you do all day! This was a revelation and turning point for our relationship, John did not want to do childcare full time and therefore never expected me to.
3)      JT: We are all selfish. Level the playing field so no one feels they are sacrificing too much. Test yourself against these thought experiments to test how equal your careers are:
  • You are offered a dream role in a new city, but taking it would put your partner out of work…do you take the job?
  • Your commute is ½ hour long, your partner’s is 1½ hour…do you move?
  •  For one intensive month your partner has to work long days to finish a project and you have to do 90% of the childcare with a negative impact on your job…do you take the hit graciously?
So far, so easy? But now shrink the margins – the difference in commute is only 15 minutes, the unbalanced childcare extends to 2, 3, 6 months. Who gives first, whose set point is lower, to whom should it be unbalanced? Like salaries, the snap shot is probably misleading and career balance should be viewed as a career average rather than a single point in time. This does have an implication, if your partner took at least 6 months off as maternity leave, you will probably have to swallow the odd solo bath time! Removing friction can help here, big holidays are nice but using that money to get someone else to clean the house means fewer arguments about the dishes that neither of you want to do after a long day.
4)      Pay dads more! The 2nd six months are expensive. At the moment, the paternal part of shared leave is only covered by statutory pay by most companies. This makes it economically unviable for many families. We should learn from Scandinavian countries; where parental leave is shared in the fullest sense with full pay for a year, to benefit all of society.
5)      Finally, guilt is a wasted emotion. There will always be compromises in the choices you make, and it is not possible to give 100% of your time and ability to being both a mum and a professional. I feel guilty at work for not being at home and guilty at home for not being at work. This is normal and unavoidable but doesn’t help me do either job better. JT: I confess that I too feel guilt (I have pretended to Charlie that I don’t). But it is a worse kind – when I take time off to be with the kids I feel like I should be at work which takes away from the fun of being with them. Turning the phone off helps.

In conclusion, we are in no way saying that having both parents work is best, what we are saying is that for those of us who choose this path, it would be nice if it was a bit easier. We believe there are ways of making it more straightforward with more productive and happier workers and parents. Ideally, there would be less pressure on mums to stay home and not work; but equally importantly there should be more support for dads who want to be involved in raising their own kids.

Thursday, 28 September 2017

Publishing Do's and Don'ts

This first appeared on Times Higher Education

Do: Get writing.
Every paper has a home. Sadly papers do not write themselves. If you don’t write it, no one else will. This applies at all stages of your career. The writing process clarifies ideas, identifies gaps and suggests key experiments. You may be doing the best research in the world, but work unpublished is effectively work undone. Knowing when to stop, when that one last experiment is not needed and it’s time to wrap up is critical. Careers falter on lack of publications and there are many roadblocks to getting your work published, don’t let one of those roadblocks be you.
Don’t: Aim for perfection.

Done is better than perfect. Yes the work has to be of a high standard, but no paper will ever hit perfection: aiming for this impossible goal will delay publication. I like to use the unlikely analogy of rifle cleaning. No matter how much you cleaned a rifle, the inspecting officer could always find hidden dirt: however, if you took it 90% clean, though they still found fault, but that fault was fixable. Ditto papers, even if ‘perfect’ the reviewers will always find fault. Better to leave a fixable hole and get published than get scooped aiming for the moon.

Friday, 21 July 2017

Better Metrics

This first appeared on Times Higher Education

So the UK HE sector, has just been evaluated again (the teaching excellence framework: TEF). This brought good news for some and bad news for others. And that is the problem with evaluation, it is divisive – there are winners and losers. This moves academia away from being a collaborative, team-effort with a free flow of ideas between individuals and a pooling of talents to a fight to the death for limited resources. However, regardless of your opinion about the validity of the process, external assessment of higher education is unlikely to disappear anytime soon. This means we need to think about what is being assessed and to shape it so that it builds rather than subdivides.
Whilst the assessors claim it drives up quality, assessment can put undue pressure on the people being assessed. And it changes the focus to the metrics being assessed. We should be in higher education because we love doing it. But, since the sector has moved away from the generation of gentleman scientists performing research on their country estates in their spare time, to be involved in higher education, you need a space to do it, income to support you while you do it and funding to pay for it. And to get these things you need a career. And to get a career you need to tick the boxes.
Call it what you want: gaming the system, focussing resources for maximum effect, metric based performance criteria, we all do things to progress our careers. If you don’t think you do, you are either: in denial, stuck in a scholarly Stockholm syndrome where you think this behaviour is the norm, a Nobel laureate or about to get sacked.
Changing the metrics is the easiest mechanism to deliver change, giving clear guidance and enabling senior staff to support people as they advance. But the new metrics need to be meaningful and critically, understandable to everyone involved. Poorly constructed metrics can lead to the loss of potential by cutting careers off at an early stage, perpetuate gender bias if they are worded in an overly aggressive fashion and can pile on unacceptable levels of stress, especially when used as a tool to manage out rather than support and develop.
The best metrics will align to support and deliver performance, scientific excellence, service and personal development. Easy to say, much harder to deliver. The San Francisco Declaration on Research Assessment (DORA) is a start, but focuses mainly on research output, without assessing the academic in the round. Here are my suggestions for underpinning principles for new metrics:


  1. Holistic: we need to demonstrate that we are improving and growing, that the work we are doing is of value and that we are making a meaningful contribution to the community, both the greater community and also to the institutions in which we are based. Contributions to these communities – through teaching, service, outreach, mentoring need equal weighting to grant income and papers. Not just as boxes to be ticked, but actual equal weighting.
  2. All informed: both the assessors and the assessed need to understand, accept and stick to the new metrics.
  3. Supportive: It takes time to discover your academic niche – not all of us are great teachers, not everyone can be on TV, only 9 of us a year are going to get Nobel Prizes. There needs to be space to develop our talents and not to be cut off after three years because you failed to get a million pounds in grants and the cover of Cell. 
  4. Simple.


If metrics can deliver academic excellence, personal development, community engagement and the greater good, then we might get the sector that we are all working hard towards.

Tuesday, 4 July 2017

Lab culture: Part 1. What is lab culture?

What’s the difference between a Lab and E.coli … E. coli has culture.
Lab culture is surprisingly hard to describe, in part because it is so varied.
Lab culture is underpinned in the science. There are clear differences based on the discipline: a group waiting for their solitary slot of the year on the particle accelerator are going to have different priorities to a group conducting field work on the mating habits of the common sparrow. This seems obvious, but there are subtle differences in sub-speciality. Take the approaches to studying influenza virus as an example: a virology group working on viral replication are going to think about the problem differently to an immunology group working on flu vaccines who in turn are going to approach it differently to an epidemiology lab working on transmission dynamics.
There are also differences in the approach to science. Amongst others, there are n=3 is good enough labs and there are labs that need to iron out every wrinkle, even if it means never publishing. There are labs chasing the latest fashions and labs working on an obscure niche of the field. There are ‘translational’ labs working towards to a specific product as that will improve human life and ‘pure’ science labs seeking to discover some greater truth - each convinced their own approach is best. There are pile ‘em high sell ‘em cheap labs producing PhD likes sausages and bespoke hand crafted labs with only a single member. There are great labs to work in that generate nothing and shitty labs to work in that get Nature papers. And of course most labs are a mixture of everything.
But it doesn’t end there, lab culture extends into your social life. In some labs everyone stays at work till midnight but only a subset of those where people are actually working as opposed to messing about on Facebook looking busy till the boss leaves (presenteeism). In some labs everyone goes to the gym and power lifts whilst other labs binge drink. Some labs stop religiously for tea together at 10am and some labs no one talks to each other – simmering in resentment. More than anything else, the culture of a lab will shape your experience in the lab now and potentially going forward into the rest of your career (and possibly personal life: intra-lab weddings being not infrequent).
Since lab culture is key to your happiness and productivity, it is important to identify what works for you and then identify a lab that aligns as closely as possible to this. We would argue this is more important than the material detail of the project. Most scientific skills are transferrable; being miserable for 3 years and then quitting is not. John started in Drosophila lab and now work on human vaccines: Charlie started in a parasite lab (not entirely coincidentally in the same department) and moved through mast cells, asthma, pharma and charity. It is better to walk away from a lab that does not align with what you want than suffer for 3 years. This may be hard to imagine when you have spent an eternity looking for a PhD position: but a bad PhD is considerably worse than no PhD.
Identifying what you want takes some hard soul searching; harder still is finding the soul of a lab before you work there. There are some ways to sniff it out – it helps if you can do a 1+3 type PhD scheme and shop around for a lab, likewise masters or bachelors projects in the same lab or department can help. Some labs will have such a strong reputation (for good or bad) that it will precede them. It also gets easier as your network grows. Do some research, LinkedIn stalk the lab and work out how many people have worked there ever and what they have gone on to do, look at the number of publications and where they go. Failing knowledge you have to ask questions. Try and visit the lab before doing an interview, ask other people working in the lab what it’s like to work there but also snoop a bit in the lab and offices. Are they tidy, dirty, covered in ‘hilarious’ posters, is there evidence of communal food in the office, are there rotas for cake club or other social interactions. Interviews are a two way process, don’t waste questions about the start date, ask questions that probe lab culture. This is a tricky line to take as the questions need to be open without being confrontational and to make you sound employable: how often do you meet with your team is reasonably non-confrontational. Take some time to think about it, balancing the emotional with the rational.

At the end of the day it is always a bit of a punt and you may have to settle for good enough and paid rather than perfect but unemployed. However, once you’ve got your foot in the door there are ways to change things.

Monday, 3 July 2017

Lab Culture part 2: Shaping lab culture

We’ve established that the culture of the lab you work in is going to have a major impact on your life. Having taken the fantastic advice from our previous article, you went and picked a lab with the perfect culture for you and then lived happily ever after. The End, or is it?
Something’s changed.
The direction of the work can change; either driven by new funding opportunities (or lack thereof), or new techniques – with this week’s cutting edge technique becoming next week’s kit. The people doing the work also change; this is accelerated by the current climate where high-throughput, short-term contracts are so common. Changes to a lab’s culture can be positive; a coming together of like-minded individuals, with a common purpose at a similar stage of life. But they can be negative; it only takes one poorly managed psychopath to tear apart the fragile ecosystem of a lab.
I’ve got the power
These fluxes mean that lab culture isn’t set in stone and the power for change is in your hands. But in order to change lab culture you need to understand the different agents that shape it and the degree of leverage they have.
Institutional Change
The most remote agent influencing lab culture is the institute. Institutional influence is asserted through the principal investigators it hires and the expectations it has of them. The institute also influences broader interactions outside of your group through meetings, seminars, away days and social events. These extra-group interactions can be critical when you have hit a wall, both scientifically and socially. Whilst you can shape these wider interactions – departments often have unspent budgets for social events and are looking for an enthusiastic person to organise things – by  and large there isn’t much you as an individual can do to shape the broader policy:unless of course you are head of department!
Power to the people
The second driver is the group itself. People make the lab, they are the ones who go to lunch (and the pub) with you, spill stuff into your bench space, order replacement chemicals (before using the last aliquot), book key pieces of equipment for weeks on end or help you with that out of hours timepoint. Every member of the group can exert a positive or a negative effect on the culture. The degree of influence you have in the group will be a product of seniority, time served and personality type.
The simplest way to have a positive impact is to spend more time together: out of the context of work. This doesn’t have to mean going to the pub, simple social events – a cake rota or a bake-off – anything that gets everyone in one space and talking is beneficial. How you behave in the lab is also important; not being a dick is a good start. Contributing to communal tasks, for example tidying up, collecting parcels or reporting broken equipment, leads to a better lab culture. But think about how you let others know about your contribution. There is no point in being a silent martyr: you are only going to end up resentful. At the same time, don’t weaponise your contribution. Emptying bins then sending passive aggressive emails about full bins leads to a worse culture than not emptying bins in the first place.
Like a boss
The final (and main) driver of lab culture is the principal investigator (PI). Even seemingly unengaged PIs set the lab culture: through the staff members they choose, the bad behaviours they ignore, the field they work in and their approach to that field. Some of the things that can be done as a PI to build a good lab culture include:

  1. Attitude. Spend a small amount of time thinking about what type of lab you want to run. If you are going to run a results-driven sweatshop, at least let it be a conscious decision rather than a default position based on your own postdoc experience.
  2.  Altitude. Running a lab is not dissimilar to being a parent. There’s a balance between being too close (helicopter) or too remote (satellite). Different people need different things at different times. Only by getting to know your group will you know the level at which they work.
  3. Break the bread. Take your group for a drink or an ice cream. Celebrate every win – papers, grants, vivas. When you have time, eat lunch with the group. Have an away day. Invite the group to your house. These small social interactions will help and energise you too. However, remember it helps to have some distance between you and your team: management’s not a popularity contest; you may have to make difficult decisions which can’t be done if you are always trying to be “besties with your crew”.
  4.   Care. Take an interest in your team. Ask deeper questions about their lives outside the lab and actually listen to the answers. Remember what they said they were going to do at the weekend and then follow up on Monday. Even if you are not interested, fake it; 5 minutes of engagement can go a long way.
  5.  Return to the lab. You may have got to the point where the majority of your effort is focussed on writing (papers or grants) and it is more efficient to get the people you employ to do the labwork, to do the labwork. However, not being in the lab, you will miss a substantial part of the group dynamic. Treat yourself to an experiment every now and then, you will get a much better sense of WHAT is and isn’t working and equally WHO is and isn’t working. As a side benefit, people tend to be much chattier when pipetting so you can catch up on the gossip.
  6. Be the best you. Behaviour in your lab reflects you. This is partly because you have recruited people just like yourself (which we all do) and partly because as the figurehead of the lab, you are the main role model. Bitching about colleagues to your group, however tempting, will lead to a culture of bitchiness. Not sweating the small stuff will lead to a more relaxed atmosphere, but it may mean things get overlooked. Losing your rag every time a mistake is made won’t stop mistakes, but will mean people hide mistakes from you.

Whatever your role, the way you act will influence the culture of the lab; and whilst getting the science done is the priority, doing it in a way which is collegiate, supportive and fun makes it less painful for all involved.

This first appeared on digital science