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

Tuesday 18 December 2018

What is up your nose?


We are interested in the contents of your nose, not at the level of hair, bogey and the occasional finger, but at the level of the complex microbial community that lives there and how it is associated with respiratory infection. The makeup of this community has been interrogated through sequencing (the airway microbiome) with indications that some bacterial communities may be associated with health and others with disease.

A bacterial diet

However, what the bacteria in the airways eat to survive is less well understood. One tool that may help us to characterise which biochemicals in the airways bacteria can use as food is called metabolomics. This uses liquid chromatography, to separate the biochemicals, and then mass spectrometry, to interrogate what they are. Comparing the mass spectrometry data against a curated library, we can then determine which individual biochemicals are present and their relative abundance. This tool has been used widely to investigate changes in the blood but has not been used much to interrogate the airway.

Blotting paper 2.0

The aim of our recently published study was to compare methods for sampling the airway metabolome. We looked at two standard techniques – nasal lavage (flushing a millilitre of saline through the nose and recovering whatever you can – quite a lot never comes back!) and induced sputum (getting people to breathe in an expectorant and then spit in a cup). We also used a newer technique, that had never been used for metabolomics sampling, called Synthetic Absorptive Matrix (SAM) strips. These are hi-tech blotting paper and have been used to recover other types of sample from the airways, including antibodies and cytokines. You can watch a video of their inventor having them put up his nose here. We looked at the use of these SAM strips in both the upper airway (via the nose) and the lower airway (via a bronchoscope). In the traditions of Barry Marshall (though I doubt I will get a Nobel prize for this), I volunteered to be one of the subjects for the sampling; the nasal wash, induced sputum and upper airway SAM were all fine, but having a bronchoscopy was fairly unpleasant.

It’s good to share

Having collected the samples, we then outsourced the running of the metabolomics to a company, called Metabolon in the US. This choice had mixed reviews, but I think it is ok to outsource, increasingly labs are outsourcing some of the more specialist analysis approaches – sequencing, transcriptomics, metabolomics. This makes sense in terms of time, expertise and access to equipment. Specifically in the case of metabolomics, outsourcing gave us access to a much larger curated library of samples, giving us more information from our samples, the biochemicals were also grouped into families, enabling us to interrogate the data more easily.

Sooo much data

From the point of performing the study to publishing it has been a lengthy process. In part this was due to the complexity of the dataset. We had approximately 14,000 data points – which may be small compared to some types of project, but when you are used performing focussed studies on individual mediators it was quite a step change. This was combined with a bewildering list of biochemicals, most of which we had never heard of – 1-stearoyl-2-arachidonyl-GPC anyone? In the end, through the power of the R programming platform and a very talented PhD student, we have ended up with a paper that uses a wide range of graph types, all of which aimed to compress the data into a meaningful form.

Food for the Pseuds

So what did we find? In total, 581 biochemicals were recovered from the airways belonging to a range of different families. When we compared the relative abundance of the these biochemicals between the different sampling techniques, we saw that the SAM strips gave us a much greater recovery of biochemicals than the other approaches. Since we were interested in how the airway metabolome enables bacterial colonisation, we screened some of these biochemicals for their ability to support bacterial growth. 35 of these biochemicals were able to support growth of the opportunistic airway bacteria Pseudomonas aeruginosa, including a number of sugars and amino acids.

A microcosm in a nostril

The airways represent a fascinating ecosystem because they are nutritionally more restricted in terms of the range and specific concentrations of any one biochemical compared to say the gut, but at the same time the nutrients are constantly refreshed. The balance of biochemicals in the airways shapes the bacteria that can live there, and we believe that this could be dysregulated in disease. By developing the tools to sample the airway metabolome, we are now one step closer to understanding how changes in airway biochemistry affects infection.

Saturday 1 December 2018

How do you build resilience

This was a co-authored piece with Dr Cecilia Johansson (Imperial College London)

At the recent British Society for Immunology (BSI) Early Career Training session in London, we were tasked with talking about tools to help immunologists improve their resilience. This was identified  by the BSI’s ‘Careers in Immunology’ report as an area that early stage (and middle and late stage) immunologists struggle with throughout their careers. So you probably don’t need us to tell you that a career in science can be difficult. Whatever stage you are at, there are always new hurdles to surmount and rejections to overcome. Part of the phenotype of the successful scientist is resilience: resilience in the face of experiments failing, resilience in the face of papers being rejected, resilience in the face of short term contracts, minimal wages and a terrifying lack of job security. As resilience is "the capacity to recover quickly from difficulties" – how do we build/enhance our resilience?
We have identified three sources of resilience that you can draw upon: within yourself, outside yourself and outside your work.

The Struggle Within

The first source of resilience has to come from within yourself. There are a number of tricks that we think can help:
  1. Mindset. Carol Dweck is a Professor of Psychology at Stanford University; in her book MindSet,1 she identifies the strength of a growth mindset, which means looking for the opportunities to improve yourself in any situation. So instead of saying ‘reviewer 2 is an idiot’, reframe the situation to say ‘how could I have made my writing more clear so that even reviewer 2 could understand it’.
  2. Other people. Other people’s success can be a source of strength, or not: we have two different approaches to deal with it.
    1. Never compare up (John’s approach). With the internet to hand you don’t have to look very far to find a more successful immunologist than yourself. It is then very easy to slowly sink into despair as you read their endless CV of success. Don’t do this! Alice Prince at Columbia very clearly describes how people’s CVs are not an honest reflection of the route they took.2
    2. Inspiration (Cecilia’s approach). Use amazing people around you as role models. Have a lot of them and use their skills/behaviour/mindset as motivation.  
  3. Behaviour. It is not what happened, it is how you react to the situation that decides the amount of resilience needed. Your values, mindset, beliefs, and current state of mind all influence how much resilience you have: when you are super stressed and over-worked it is much harder to cope. Reflect on how and why you react to a particular situation and think of how you can improve your coping strategies.
  4. Celebrate. Make a point of celebrating successes big and small: papers, grants, experiments for both yourself and everyone around you. Apply the perspective of time to your progress: taking a longer view smooths out the lows and demonstrates an upward trajectory. Pause and take stock of the past three months, one year, five years and identify what went right.
  5. Make plans. It is difficult to assess your progress without a plan. What do you want to achieve in the next three months, one year, five years. The granularity of the detail can fade as you look further into the future.
  6. Pause and take care of yourself. In a stressful life/period, it is very easy to forget yourself. Find ways of manage your time (as time is precious and we never have enough) and your stress levels. Mindfulness (essentially meditation) can be a very helpful tool. It doesn’t need much more than closing your eyes and focusing on your breath or the background noises for a few minutes to re-wind and re-set.
All of these approaches link to good reflective practice – studying your own experiences to improve the way you work. There are times when everything can get on top of you and you have to take time to step back. However, occasionally, it is not possible to do this alone and this is where you need to the second source of resilience, other people.

Everybody needs somebody

We all need support from other people. The Ancient Greek language has multiple different words for love/ support, and while the type of support we need most will vary from person to person and with time of life, these different types provide a useful framework for thinking about our interactions with others. This support can come from both within science and from your broader circle of friends and family.
Agape refers to love from a parent to a child, but more broadly reflects support from a senior figure to someone more junior. Don’t restrict yourself to one role model or mentor, you don’t even need to have met them (e.g. CJ looks to Cheryl Sandberg, COO at Facebook3; JT has learnt a huge amount from Stephen King’s book On Writing4). Take every opportunity to meet new and inspiring people. But also look inwards, most organisations (including the BSI) run mentoring programs. And remember different people will be useful for different types of advice/perspectives.
Eros describes the love of a partner. Now this is far from being a lonely hearts column, but we both draw great strength from our partners. The family network (partner, children, parents, cousins etc) is also a huge source of support.
Finally, but not least, Phillia love of a friend. Assembling a group of like-minded individuals is really important. Start in your PhD. Long hours spent moving colourless liquid around in labs are the perfect time to bond. Immunology is not a big field: as you progress with your career, it is amazing the times your paths will cross and re-cross. If nothing else, your PhD cohort are good for free beds in foreign cities. But the hope is that you can rise together on a common mutually supportive wave.5

Hit the road Jack

The final source of support is the realisation that this is just a job. If can feel all consuming, but it is still just a job. It helps to take a broader perspective. Again this comes back to good reflective practice. In parallel it is vital to have a life outside work (more work to live than live to work). This is not always easy, especially if you are juggling work and family commitments. But find outlets that you enjoy, without feeling the pressure to excel at them: bake but don’t aim to win Bake Off, run but don’t aim to win marathons. These other activities serve the same purpose as mindfulness – they break the loop when work is getting on top of you. Try to remember why you are doing/chose to do this job and the many positive aspects it brings.
A career in immunology has peaks and troughs. It’s ok to find it tricky and to admit to other people that you find it tricky. Recognising and celebrating the highs and learning tools to negotiate the lows can really help.
John TregoningSenior Lecturer in Immunology, Imperial College London. Twitter: @DrTregoning
Cecilia JohanssonSenior Lecturer in Respiratory Infection, Imperial College London. Twitter: @cjohansson_lab 

Further reading

You can read more articles from John on his blog: drtregoning.blogspot.co.uk. References for the article are below.
  1. Dweck, C. S. Mindset  the new psychology of success. Updated edition. edn,  (Random House, 2016).
  2. Prince, A. Omissions from a National Institute of Health (NIH) biosketch. PLoS Pathog 14, e1006896, doi:10.1371/journal.ppat.1006896 (2018).
  3. Sandberg, S. Lean in: women, work, and the will to lead. First edition. edn,  (Alfred A. Knopf, 2013).
  4. King, S. On writing: a memoir of the craft. Scribner trade paperback edition. edn,  (Scribner, 2010).
  5. Tregoning, J. No researcher is too junior to fix science. Nature 545, 7, doi:10.1038/545007a (2017).