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

Friday, 25 May 2018

Flu and our poo


There are various outlandish estimates about the numbers of bacterial cells there are on your body compared to the number of your own cells. Wikipedia informs me that current guestimates put it at a 10:1 ratio, with approximately 100 trillion bacterial cells per adult human; which is the kind of number that a stressed scientist makes up when the answer “I don’t know but it’s feckin’ loads” won’t suffice. Our guts are particularly rich in bacteria, and it is estimated that 30% of every poo is dead bacteria. We don’t really know for certain what all these bacteria do, quite a lot of them are probably just along for the ride living off dead skin cells and sweat. But there is a small proportion of these bacteria that we rely upon for all kinds of useful things, like breaking down our food properly, training our immune system and fighting off the bacteria that make us sick. Finally there is another group of bacteria that are just waiting in the wings to cause infection, often pouncing when we are at stressed or tired.
Collectively the bacteria that live on or in us are referred to as the microbiota and the ecological communities that they make up are called the microbiome. Our knowledge of this superficial (using its proper meaning of at the surface) second life has exploded in the last decade, mainly because of our ability to read DNA cheaply and easily. There has been a huge number of studies that have reported a link between our bacterial fellow travellers and a huge range of body functions. Some of which make some sense as the bacteria at least live at the same site as the disease including obesity, diabetes, asthma and tooth decay and some that require a more conceptual leap including mental health and autoimmunity. These links have also led to some outlandish ideas for new therapies, including faecal transplant (which is almost precisely what it sounds like) to reduce gut bacterial infection and ‘vaginal seeding’ of C-section babies.
Now that I have mentioned the obligatory facts about the microbiome – it outnumbers us, it has something to do with health and people are utilising it for weird therapies – I can concentrate on what we did in our recent paper. Given the myriad associations between the microbiota and health/ disease it is important to understand what shapes these bacterial communities. In particular we wanted to know if infection at one site, the lung, would change the bacteria at another, the gut. We looked at two important respiratory pathogens, respiratory syncytial virus (RSV) and influenza. Following lung infection, we observed a transient but significant change in the bacteria present in the guts.
One of the offshoots of studying the microbiome is that you need to learn (or relearn) your Linnean classifications (which for those of you that can’t remember go Domain-Kingdom-Phylum-Order-Family-Genus-Species: so for example humans are Animals-Chordates-Mammals-Primates-Hominids-Homo-Homo sapiens). We saw a shift in the bacterial phyla with a big decrease in the Firmicutes phyla and an increase in the Bacteroidetes phyla. Further subdividing within these phyla we saw a decrease in the Lactobacillaceae family and an increase in the Bacteroidaceae family. More strikingly, when we analysed at an approximation to the species level, we saw different species profiles with each experimental repeat. This suggested that lung infection wasn’t specifically affecting one or two species, rather it was changing the gut environment in such a way that one phyla of bacteria (the Bacteroidetes) would benefit at the cost of another (the Firmicutes). This change was acute and transient and by the time the mice had recovered from infection, their microbiome had also recovered.
Like most of science, this study acts as a starting point, asking more questions than it answers. What does it all mean? Frankly your guess is as good as ours. There is some suggestion that Lactobacillus are ‘good bacteria’, mostly from Yoghurt manufacturers who are trying to claim that a fruity, milk-based pudding is in some way good for you. One speculation is that if the bugs in our gut produce things we need to be healthy, lung infection, by disrupting the gut microbiome, may amplify sickness. But we would need to replace the ‘good’ Firmicutes and see an improvement of disease outcome to demonstrate this. Why is this happening? Again, we don’t have an answer. We had one tantalising result, which was that there was an increase in proteins associated with airway mucus in the guts, which occurred at the peak of point of bacterial change. Many of the bacteria in the Bacteroidetes phyla can utilise mucus as an energy source and so the swallowed mucus may support their growth. As I type, we are following up on both of these questions – so stay tuned and we might just have the answers, or more likely more questions!

Wednesday, 16 May 2018

Running up that hill: running, pop-songs and mental health

I wanted to share how running helps my mental health. I’ll admit this is a pretty self-indulgent piece, but since having a blog in the first place is self-indulgent, that shouldn’t be too much of a surprise. That said, you should definitely read on, even if only to test your knowledge of pop music.

The overstated health benefits of running!
I am focusing on the mental benefits as I am not entirely sure of the long term physical benefits of running: I am currently laid up with a torn calf muscle, my ankles and knees are pretty ruined, my tendons have shrunk so far that I can barely touch my shins let alone my toes, I’m pretty sure I’ve broken a bone in my foot more than once and the less said about my toenails the better.

However, running does, for me, have clear mental health benefits:

1.       Lose yourself. I have a pet theory that my sub-conscience does most of my problem solving; which is a convenient excuse when I am caught staring into space. But in order to problem solve, my sub-conscience needs some space in my head. Mindfulness (the corporately acceptable face of meditation) comes to the same thing – clearing the thoughts from your head. For me, running, particularly to music, clears everything else away. Occasionally, I take this to extremes by running in the woods at night with a head torch and music cranked to 11, which earns a few odd looks, but is amazing. Some people claim to power their way through work problems whilst they run, but I am too busy concentrating on remembering to breathe and the effort of putting one foot in front of the other to do this.
2.       Working 9-5. We are all productive at different times of the day. I get my best thinking done in two blocks 9-12 and 4-7: there is often dead time between these blocks and problems stay unsolved regardless of the effort spent forcing them. It is far better for me to do something else in the intervening time. This is where having a set of running stuff at work really helps, when I hit a low ebb I can head out the door for 30 minutes and come back refreshed (mentally if not physically).
3.       A small victory. Academia is beset by failure: be it experiments, grant or papers. Sometimes I need little wins. Running can provide wins through running fitter, further or faster. Apps have revolutionised incremental gains in running and whilst there are few wins smaller than knowing you were the 17th fastest person across Waterloo bridge on a wet Wednesday in November, it beats the old method of ‘winning’ against random strangers running in the park who don’t even know they are in a race (though admittedly I do this too).
4.       Thank you. One of the major stressors at work is in comparing myself to others, losing sight of what I have achieved in the comparison. Running provides moments of wonder and gratitude: turning the corner to see the sun rise over the sea, or the light dancing on a wheat field or even just the smell of rain on the London pavements. Likewise, going on the same route year round gives a great sense of the changing of the season. Admittedly the endless slate grey of the British Autumn/Winter/ Spring can get a bit monotonous but eventually the joyous day comes when the greenery bursts into life. Restoring the perspective that I often lose.

All of these benefits are variants on a theme: they take me out of myself, focusing my thoughts on simple things. I am at my least healthy when I get caught in a loop: be it funding, staffing or logistics. Interrupting this loop with something else can be enough to shut it off or get me to focus on the solution not the problem.

Of course there are other ways I can achieve the same state. They are mostly outside: walking, camping, gardening, playing football or listening to live music. But where running has the edge is the ease and convenience. You don’t need anyone else; you only need a pair of trainers. It is also incredibly flexible, it can be squeezed in as part of the commute - though my fellow commuters on the 6:24 from Waterloo may be less grateful as I sweat my way home. It is also highly portable, I make every effort to take my running things when I travel with work and this has led to some of my favourite runs – along the seafront in Reykjavik as the sun sets over the sea, in the rain in Brussels, on a beach in California as dawn breaks.
Sunset over Iceland
Daybreak in California










As I said from the outset, this was largely a self-indulgent piece, I enjoy running, it helps me and wanted to share that feeling. Of course the reality falls short of the picture I paint here. There are often times when I don’t want to leave the house, when all my muscles ache and there was even a time when I got overtaken by someone dressed as a rhino. And while it’s not for everyone, I think the underpinning idea – doing something that takes you out of yourself is enormously beneficial. And if you found this a bit preachy, remember it could be worse – I could be a cyclist.


PS – did you spot them:
Runing up that hill: Kate Bush
Lose Yourself: Eminem
Working 9-5: Dolly Parton
Thank you: Dido
And a bonus point for spotting the Spinal Tap reference.

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.