Sunday 14 September 2014

cascade SMASH

As it was coming to the middle of summer I really wanted to make a summer ale; one similar to American pale ales, which are bitterly hopped with hops like cascade (the floral grapefruit-like ones), light textured and bodied but a bit sweet. For this I followed a standard pale malt + sweet crystal malt + lots of hops at early and late timepoints. No dry hopping was used. A standard ale yeast was used. This ale turned out pretty well and tasted like the usual Brewdog-kind of pale ale. Not the most creative but tastey.

Monday 4 August 2014

towards a high-resolution understanding of hepatitis C virus

HCV virions
Viruses are sub-microscopic parasites of cells. What this means is that despite our immense interest in them, they are very difficult to observe and study using your eyes or even traditional light microscopy, which is the mainstay of biology over the last few centuries. This is annoying because we are interested in understanding what viruses look like because of what they tells us about their biology as virus particle structure affects many aspects of its lifecycle, such as cell entry, replication and transmission. 

These questions are no more interesting than for HCV, an important human pathogen that has chronically infects between 130 and 150 million people worldwide and leads to between 350,000 and 500,00 deaths a year. Infection often lead on to chronic hepatitis, cirrhosis, fibrosis, hepatocellular carcinoma and eventually liver failure and death. Although there are now effective drugs targeting HCV, HCV and associated diseases are likely to continue to be a public health issue in the future because of their prohibitive cost. We do not yet have an effective vaccine to protect against the virus either. 

One avenue to aid development of antivirals and vaccines is to understand HCV particle (virion) structure and the pathways that promote its assembly and its entry into cells. The catch is that HCV has been extremely challenging to manipulate in the lab under experimental settings. However, a paper published in the journal PNAS, (free here from the Charles Rice lab in New York (first author: Maria Teresa Catanese) has shown the characterisation of HCV virion structure using a powerful microscopic technique: cryoelectron tomography (cryo-EM), which has improved our understanding of HCV biology. The continuing use of this imaging technology combined with models of HCV entry and assembly may aid in the development of novel HCV drugs and vaccines. 

Sunday 27 July 2014

wheat beer #1

wheat beer #1

One of my next beers I wanted to make was a wheat beer in the style of Hoegarden. I had previously tried out this style earlier this year (see here). This beer was nice enough but it was so alcoholic and sugary that it was near-impossible to enjoy drinking it. This next beer was an attempt to rectify this. 

To improve upon the last recipe I made some alterations, namely in reducing the amount of input to bring down the OG. I also simplified it a bit and took out unnecessary carapils and wheat whole grains.  The recipe was altered so as to allow 4.5 litre brewing.  

Sunday 22 June 2014

microtwjc analysis 2. unique tweeters

When considering participants in #microtwjc, we can also measure the number of unique tweeters, tweeters who have not tweeter at a previous session. This allows a measure of growth of #microtwjc to new people. I have plotted unique 'new' tweeters over time for both the total tweeters and the engaged (n<1 tweeters per session) people. Again, both measures are different. But a major finding of this is that #microtwjc has continued to recruit engaged tweeters over the time. This is at a fairly constant rate, except for a couple of spikes. I've shown the cumulative growth of tweeters in the graph below. Total is growing at an average of 1.8 tweeters/session while engaged are growing at an average of 1.3 tweeters per session. Questions arising from this are: are these tweeters staying? What's the loss of engagement like? To do this I could plot tweeters per person per session. Let's try that. 

dark ale take 2.

Spoiler: it was great.

The key to good and science (and good beer) is repetition. The act of doing an experiment again and again allows you to not only find weaknesses in your thinking and doing that you might not have realised but it allows you to act on those weaknesses and improve and rectify them. This is why I tried to make another porter/stout. This was mainly because the last one had some issues (too sugary sweet/ not mellow and not enjoyable to drink). This is a stout after all; it should be relaxing to drink. Guiness anyone?

I had tried a similar recipe before (details here). The major differences between the two recipes that I planned are: lower original gravity and the addition of flavor elements that would mellow the beer out (oatmeal, coffee, dark chocolate). My thinking was that the worst aspects of the first beer were high OG and lack of complex elements (chocolate etc.). [never though of this but perhaps I shouldn't have used so much crystal].

Coffee was made in caffetiere, 4 squares of chocolate (Dark, tesco, cheap) were melted in the coffee + boiling water. Oatmeal was steeped. 

Thursday 19 June 2014

#microtwjc analysis 1.

The microbiology twitter journal club (#micrtowjc) has been going since x. This 'group' was established to allow the easy discussion of microbiology papers, data and ideas. To do this, a session is planned every two weeks (roughly) on a Tuesday night at 8 pm UK time. One moderator picks a paper that has been recently published (and is usually open access) and then uploads a brief summary and questions to be discussed come the next Tuesday. 

This arrangement has been going on for about two years now and we have not had a chance to evaluate what we have done. In essence, we have conducted a two year experiment into using science communication. By doing a brief eye-balling online it looks like #microtwjc is longest running, functional twitter journal club. The original twitter journal ( ran for 2.5 years (June 2011 - December 2013), with a half-year break between June 2013 and December 2013 (other breaks were taken). This means that #microtwjc affords an optimal chance of getting something useful out of its study. 

For the last few months we have been trying to gather as much data about #microtwjc as we can. This covers number of tweeters over time at each session, number of tweets per tweeter per session, papers discussed, journals most chosen etc., etc. These data can be used to assess the worth and potential for #microtwjc to be better in the future. It also serves as a model to understand the use of twitter and social media for science communication and public engagement with science in the future. 

In a series of posts I will try and analyse these data with a hope of finding some useful knowledge and wisdom about #microtwjc. You can view the data here.

A brief description of the methods to get the numbers discussed in this post. 1) each session was logged in storify or topsy format. 2) logged on to each site and searched for each session by date, name etc. 3) went through and counted number of tweeters and number of tweets they made. *this data collection was carried out by a number of the moderators of #microtwjc* . You know who you are. If any of you want to explore these data further, go do it. It's all open. 

Firstly, I took the numbers and divided them per session (fig 1. ). What I quickly realised is that many tweeters tweeted only once, advertising the session, apologising for not being there. I felt these people were not 'engaged' with the session and as we are primarily interested in 'engagement' I decided to clean up the data and remove them from later analysis (posts to come). The engaged tweeters are shown in magenta (fig. 1.). The average tweeters per session was higher in the non-engaged group (As expected) with an average of ~8 compared to ~6. The spread of tweeters was also greater, mostly accounted for by session 1 (fig. 2 green). 

fig 1. number of tweeters: total (green); tweeters tweeting more than once 'engaged' (magenta).
 Fig. 2. shows the data from fig. 1. shown over time for each session. This allows us to pick up peaks of troughs of activity and 'engagement'. 

fig 2. number of tweeters taking part in each session: total (green); tweeters tweeting more than once 'engaged' (magenta).

 Comparing the number of 'engaged' tweeters with total tweeters for each session we can come up with a map of engagement over each session (fig. 3.). This largely parallels fig. 2. but shows it better. 

fig. 3. percentage of tweeters who tweeted more than once per session (engaged) (orange).
I think two conclusions can be gleamed from this small analysis of #microtwjc tweets. 1) There is a more active 'engaged' community of tweeters and 2) tweeters and engaged tweeters changes over time. The reasons why are unknown. There looks to be a difference between years 1 and 2 (session 1 - 26). Your comments are welcome below. 

The hope is that these data can be compiled, analysed, uploaded onto a data repository (figshare) and then use this to publish (PLoS, for example). This process will be completely open and collaborative. 

Tuesday 17 June 2014

basic liver biology - why things go wrong when it's infected

Being a virologist is hard. Not only do you have to know molecular biology but you also have to know cell biology and if you are interested in how viruses cause disease, you have to know anatomy and physiology. As you can imagine, while being extremely interesting, it is very time consuming This is why I have spent the last few days (weeks now) trying to come to terms with my liver. 

Your liver is pretty amazing. Chances are you take it's special role for granted but you really shouldn't. This is something that I have been thinking about over the last few months after starting a postdoc into hepatitis C virus (HCV) biology, while I pondered on what it must feel like to lose the function of your liver. To appreciate what is happening during a disease like viral hepatitis, you have to understand how the liver does it job when it's not sick. This post will hopefully be the beginning of a series of blog posts aimed at trying to understand HCV infection and pathogenesis and how my research fits into it. FYI - I have not included any references in this post because what I am writing is established understanding in basic textbooks. This post will act as background as I continue my exploration of the liver and HCV.

You probably won't have seen your liver and your only experience of its metabolic work will have been after you've had a few drinks and you don't remain inebriated for too long. But it also does much, much more. Your liver carries out a complex array of functions, very difficult to summarise in a post like this (but I'll give it a go). Your liver operates a central role in keeping you alive by carrying out a 'biotransformative' role, lying between absorption (your intestines do this) and excretion (your kidneys do this). Biotransformation exists as two major metabolic functions: altering and breaking down molecules (catabolism) and synthesising them and releasing them into your blood stream to feed the rest of your body (anabolism). Another variation in this role is to break down toxins that can damage your body and it can even release hormones and bile, allowing it to function as a gland (again, variations of catabolism and anabolism). It can also store glycogen, an important carbohydrate storage vessel. What did I say, it is a complicated organ, so no wonder things go bad when it gets infected. The most important feature of your liver that allows it to function as a biotransformative organ is its close association with your blood stream and to do this, your liver employs some interesting physiological tricks. But it is these tricks that open it up to infections and disease
your liver, in relation to stomach and pancreas. Note the lobes and blood supply. ( 

Anatomically, your liver is a large (1.5 kg), triangular organ in the top right hand side of your chest, beside your stomach and your intestines.  It is divided into four sections, referred to as lobes. Allowing it to carry the job of breaking down and releasing important molecules into your bloodstream, is it's intimate relationship with your circulatory system, which is composed of blood and lymph fluids. Testament to this relationship is its reported blood flow of 1.5 litres per minute. Unlike other organs it has a dual blood supply made up of two major blood vessels run through your liver, the hepatic artery, which brings in oxygen-rich blood, and the the hepatic portal vein that brings in absorbed nutrients and toxins from your small intestine and allows the blood to flow back into circulation. What makes this dual supply even more impressive is the dense network of smaller blood-circulating endothelial cells that are in near-direct contact with your liver cells throughout your liver tissue. This anatomic arrangement allows maximisation of the surface area to volume ratio of you liver for optimal biotransformation.

hepatic lobules centred around a central vein (
The liver is a honeycomb mesh of four major cell types, which for ease of understanding are referred to either as parenchymal (hepatocytes) or non-parenchymal (endothelial, macrophage and fibroblast). Your liver parenchymal cells are largely made up of a single cell type, the hepatocyte, which are arranged into single-cell thick epithelial sheets. These cells are the business end of the liver and the one that is responsible for the majority of its metabolic activity (and mass). The main aim of the liver is to maximise the interaction between the hepatocyte and the blood. To do this, your liver employs endothelial cells to form the aforementioned dense network of blood supply between hepatocytes. These endothelial cells form hollow tracts, known as sinusoids, which line sheets of hepatocytes. Two other cell types, the macrophage-like 'kupfer' cells and the fibroblastic 'stellate' cells sit in close proximity to the liver sinusoids and serve immunological, filtering and healing roles, which I won't discuss here. But have covered elsewhere before. 

If you threw these four cell types into a pile together, very little would happen, but when arranged in the way that they are in your liver, they can efficiently interact with your blood. The patterns that these cell types are arranged in come in three flavours: classical hepatitic lobules, portal lobules and acini. Each pattern describes a different spatial interaction of hepatocytes with endothelial cells. The major structural unit of the liver is the classical hepatitic lobule. Within a single lobe of your liver there are many classical hepatitic lobules, each lobule is composed of a hexagonal arrangement of hepatocytes and endothelial cells. Both the hepatoyctes and endothelial cells are organised around a central vein with five-fold symmetry. At each point of the hexagon lies a 'portal triad' of hepatic arterioles, venules and bile ducts. The oxygen-rich blood coming from the hepatic artery and then moving through the liver lobules into the hepatic portal vein. Other patterns can be observed in your liver, and the lobules can also be divided into acini (with two-fold symmetry between portal triads and the other is the portal lobules, which is relevant for bile drainage. 
cells in the hepatic lobules: not hepatocytes, sinosoidal endothelial cell and kupfer cells

And so we come to the business end of the liver. Each cell has it's own role but it is the interactions between each of them allow the liver to carry out its important job. Importantly, the hepatocytes are the metabolic workhorses of the liver, and rightly, they make up the vast majority of the liver's mass. But in order to absorb and secrete, they must be in close contact with the blood supply and it is this interaction that is facilitated by the non-parenchymal cells, which essentially bridge the liver and the circulation. Most importantly, the endothelial cells form what are known as 'sinusoids', single-cell thick vessels with 'leaky' (fenestrated with no basement membrane) walls allowing extremely easy transport of blood fluid over the hepatocytes. But what happens inside the hepatocytes? I will explore this cell type in more detail in the next post.
the hepatocyte in relation to endothelial cells (

Sunday 18 May 2014

my weeks picks (18th May 2014)


my PhD supervisor,Paul Duprex,will be on TWiV today at ASM (2 p.m Eastern Time) Paul Duprex and Julie Pfeiffer speaking about their work on 18th May!" Livestream link here:

Two new anti Hepatitis C virus drugs reach the market this year sparking any to question if HCV will be completely controllable. Here's a nice rundown on the drugs and their costs:

The first case of MERS in the US was spotted in the last two weeks First case in the U.S.: Patient traveled from KSA to Chicago, then took a bus to Indiana  expect this kind of story to continue to appear. Looks like no real evidence of spread of disease but have to wait until incubation period has ran its course. 
science. For more info on MERS, specifically testing and the apparent increase in cases, read this interview with Christian Drosten, virologist-extraordinaire. MT : Great interview with Christian Drosten on

Another coronavirus that hasn't had as much interest in comparison to MERS but should: Concerns grow over deadly pig virus. Would be great if coronaviruses would just stop...  devastating to pigs and the economy. No risk to humans though.

This week, Boston City council announced their backing for the opening of the category 4 National Emerging infectious disease laboratory (NEIDL).  update: ordnance defeated, vote was 5 for ban, 8 against

Some lovely imaging work on Nipah virus transport of structural glycoproteins within neurons: live cell imaging of nipah virus glycoprotein transport in neuronal cells fascinating


Pfizer/Astrazeneca deal breaking continues to go on but what effect will it have on UK R&D? Pfizer and AstraZeneca "The Wyeth deal alone saw Pfizer scrap 19,000 staffers".

    and an ex UK soldier sues the Ministry of Defense over vaccine-induced disease 

Ex-soldier takes on MoD over vaccine. Gulf war syndrome

Two vaccine stories this week: Do newer vaccine overwhelm the developing immune system? Debunking an anti-vaccine claim: Giving so many vaccines overwhelms a child's immune system

The Glasgow Science Festival is coming up, check out here for information . come and see me there!

Sleep deprivation for personal/work gain. Where did it come from? Thomas Edison and the Cult of Sleep Deprivation


here's where I tried to make a porter/stout homebrew. It turned out OK.


One week ago I passed my Ph.D. viva, ending 3.5 years of supervision from Paul Duprex and Bert Rima. Thanks guys!

Sunday 27 April 2014

porter take 1

Doing science all day and talking about science in this blog can get a bit repetitive. But luckily I have a hobby to rest my mind, which takes the form of homebrewing beer (only on extract at the minute). I dabbled a bit before and am now continuing to dabble after my move to Glasgow. My first 'new' homebrew experience is making a porter-like beer (maybe on the 'robust' side), which in my head was a 'less-smooth' stout. You can read the exact description here. This was actually brewed for a friend of mine's birthday in April..

Below is the recipe I followed: and results.

Virology, science, scicomm and life


Vincent Racaniello posts an intrigueing question over at Virology blog and debate ensures. What are your thoughts? why do some viruses have a segmented genome? measles versus influenza

A recent study published in the lancet looked at what viruses might be causing CNS disease in African malaria-endemic regions not big surprise that mumps virus appeared to be a big cause (also lethal) - no mumps vaccination there. But major result of this paper is that in >2/3s patients we have no idea what caused disease. Unknown viruses anyone?

": For those interested in innate immunity, read this article: " and virus! This paper looked at what RNA sequences were being recognised in measles virus-infected cells. Showed bias towards A/U-rich regions of the L gene mRNA.

PLoS published a nice short look at RSV pathogenesis and potential for vaccine design highlighting many of the issues with RSV regions but also showed where research could lead to, including new vaccines.

GAVI outlined their plans to expand impact of vaccines by 2020

More infographics. Measles infographics. I like these but think asymptomatic cases change it  I wouldlike more complicated infographics..

China and the SARS Epidemic, what was learned in ten years? Applicable to SA and MERS situation  An important history lesson if the Saudi Health Ministry are reading. But then there are also science issues: Why can't we predict evolution of MERS? Poor understanding of virus fitness. What constraints are acting?

'Don’t worry, I’m not contagious' – and other microbiological delusions are discussed in this insightful piece

it's about the little things - new virology blog. I follow the author but can't remember who... Help?  Turns out it was Mike Nicholl. Go read it. It's very good. 

For some reason I got interested n fruit bats and the Niger river in west Africa... Fruit bat annual migrations in west Africa re seasons  What links west Africa? The Niger River of course.

Other science

The Independant reported How a genetic disease was cured in an adult for the first time thi was using CRISPR/Cas9 technology. This was also done using adult MICE and high-powered injections.


The varieties of peer review: by via  . Where do you want to fit in?

Defectivebrayne did a video summary of the last paper about the designer synthetic yeast chromosome: . This is very good and informative and capturesmany of the points that were discussed at that session. 

life in general

Finally made it to Glasgow brewdog. Working my way down the list  - and then went again that week. Some great beers on showcase there.