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

Thursday, 30 August 2018

What are science?

Apparently we all fucking love science, or at least we love pretty pictures, anecdotal facts, chemical explosions and slightly preachy environmentalism.

However, science is none of these things. Science is the generation and testing of ideas; normally disproving them, in the process generating more ideas that need more testing.

Science junkies

Sadly, the day job of a scientist is nothing like the programs ‘Bang goes the theory/Tomorrow’s World/Johnny Ball Reveals All’ (delete as appropriate depending on your generation): in my 20 years being a professional scientist, there has been no time at work when I have blown anything up, thrown heavy weights into bowls of custard or put Mentos into bottles of Diet Coke.
To be honest, blowing things up at work is frowned upon and the management go to some lengths to prevent us blowing up the building (just another example of health and safety gone mad).
Highly visual demonstrations of chemical reactions are educational if phrased properly – if I do this, what do you think will happen and why? And these demonstrations can be effective for attracting the impressionable to a life of science. In effect, flashy chemical reactions are the gateway drug to scientific addiction.
At school we had a teacher who once a term gave us unrestricted access to the chemical store and a Bunsen burner; I imagined this was what it would be to be a scientist. Nowadays I don’t even get to do experiments, and yet I identify more as a scientist now than when I was doing my PhD as a space-filler before getting a “real job”.

Indoor work, no heavy lifting

So if the day-to-day of science isn’t setting things on fire, what is it?
It is immensely varied, and depends upon both the stage of your scientific career and the field you work in. But the main work of science is testing ideas. Some of which involves being in a lab, but most of which involves sitting in an office analysing the results from your experiments or coming up with new ideas because your experiments haven’t turned out as expected.
Since 99% of these ideas come from other people, another major strand is evaluating other people’s ideas and building on the back of them. And since other people need to evaluate the ideas we have, we need to be able to effectively communicate them, as written articles (papers), as sales pitches (grants) or in person (conferences).
So disappointingly, the day to day work of science is not so far removed from other professions, though we do get to wear a white coat occasionally. You need to be able to read, to write and, terrifyingly, interact with other people – very much none of the things that got most of us into science in the first place.

Wednesday, 22 August 2018

No researcher is too junior to fix science

Here is an article from Nature about how we can work together to improve science

How will you judge me if not by Impact Factor

Here is an article I wrote for Nature on the lack of clarity about replacing impact factor

From Parade ground to PI

Here is a piece I wrote for Science on how being an officer in the British Army reserve helped prepare me to run a lab

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

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.