Category Archives: Ramblings

The story of your life before you’re even born

This was a piece I wrote for a competition under the question of “why is your research important?”. It didn’t win or anything but I really enjoyed writing it and thought it might be a nice read so have now put it up here…

 

 

Over 3 billion molecules describe who and what you are. They are a combination of just 4 different types of molecules abbreviated to A, G, C and T. Those 3 billion letters are your book, and my research is to read it and understand it. This book is your genome and the letters are a representation of your DNA. Some of it already makes sense to us, for example about 2% of it is your genes and codes for proteins. However, that leaves a vast portion of ‘gobbledygook’, letters strung together in illegible sentences or in a language we don’t yet recognise. This is where I’m searching for meaning.

 

If the majority of your DNA isn’t your genes and doesn’t code for proteins, then why is it there? My research takes me into specific regions of your DNA scattered throughout your genome that are almost identical to other non-coding regions of DNA in chick, mice, fish, sharks, frogs and near enough every vertebrate organism that has had their DNA sequenced. This similarity doesn’t seem like a coincidence so my lab is trying to unravel the functions of these conserved DNA regions.

 

It just so happens that these conserved non-coding elements (CNEs) lie near genes that we know are important in early embryo development. It is because of this that we think the CNEs could affect, control and regulate the developmental genes. Therefore we believe that these conserved non-coding regions of DNA are important for the regulation of the vertebrate development system. My personal research specifically looks at what happens when this process goes wrong.

 

Development of the embryo is such an intricate process with many steps. A whole field of science is continually working out what cells divide and multiply where and how to turn a single fertilised egg into a whole organism. In vertebrates, there is even a stage where the embryos of a chick, mouse, fish, shark, frog and even human look incredibly similar. This further makes us believe that these non-coding regions of DNA that are the same in all of these organisms contribute to controlling the similar development processes. As development is so intricately controlled, the slightest changes in these CNEs could impact the development of the organism in detrimental ways.

 

All of our DNA can potentially have mutations. We can inherit these from our parents or they can be newly acquired ones specific to us. If these CNEs have mutations, could this affect their function and could this cause people to have developmental disorders or anomalies? We don’t know yet, but I sequence the DNA of people in an attempt to find these anomalies and pin down what effect they may or may not have.

 

So many parents have children with developmental disorders and are left without an answer to why. If we can’t find any mutations in the genes, we have to extend our search beyond them, to the ‘gobbledygook‘ strings of As, Gs, Cs and Ts in between the sentences we understand. Trying to find meaning in something that makes no sense to us is a difficult process. I spend a lot of my time sifting through potential variations in the DNA of these children and their parents looking for something that could potentially explain the so far unexplainable. Once a list of potential candidate mutations are found, we have to try and test the theory that they are involved in controlling the genes nearby and that this mutation causes the change in control and contributes to these developmental disorders.

 

We all have our own DNA, our own books. For many of us, we live our lives not knowing what it says but that doesn’t matter because we live healthy lives. However when things go wrong we have to turn to it to work out why and whether we can do anything to help. Science research is always stepping into the unknown, that’s how progress is made. However daunting the task of searching the remaining 2.94 billion letters for a new language may seem, understanding our genome in its entirety is essential to understanding why things can go wrong and how to treat, help or even prevent these genetic disorders.

 

My research matters because your DNA is your story, and some of the most important parts are already read before you are born.

Facebook “mind control” isn’t new

It’s all over the news, and it’s not looking good for Facebook and the researchers behind a newly published study. In case you haven’t heard, Facebook has teamed up with a group of researchers and manipulated the emotions of almost 700,000 of you during a week in January 2012 (http://www.pnas.org/content/111/24/8788.full). The paper describes the occurrence of ‘emotional contagion’ where people exposed to more positive posts on their news feeds post more positive things themselves and vice versa for sad posts. However this shouldn’t come as a surprise. I’m not saying the results are unsurprising, I’m saying that Facebook has manipulated your newsfeed to get an emotional response, and you shouldn’t be surprised.

Continue reading Facebook “mind control” isn’t new

The P word

Scientists both fear it and get excited goosebumps over it, but it’s not easy and it’s not quick. Publishing. Getting your work to a stage that’s ready to be seen by the masses, criticised by many and cited by whoever thinks it’s important.

 

I may only be a first year PhD student but already publishing my work is something I have to think about. It’s not like I’m even having delusions of grandeur as my boss has mentioned the P word to me many times now. I may not be first author on a (hopefully) near future paper but contributing is a massive step for me and fills me with excitement.

 

Before I started my research, I had very little knowledge of how publishing your work even worked. Now I’m a little wiser and have uncovered a dark, complicated route to getting your work seen. Here I outline a few of the things I’ve learnt…

Continue reading The P word

On the brink of 3 parent IVF

the metro front page 4/6/2014
the METRO front page 4/6/2014

The Human Fertilisation and Embryology Authority have confirmed that mitochondrial transfer procedures are ‘potentially useful for a specified and defined group of patients’. In addition they have said that the techniques are not unsafe but there are some critical experiments still to take place before the method hits the clinics.

Continue reading On the brink of 3 parent IVF

Pfizer meets stiff resistance to AstraZeneca takeover bid

Pfizer meets stiff resistance to AstraZeneca takeover bid

Over the weekend, the news has been relatively flooded with details and opinions of a business deal that will affect British science and research. I’ve continuously been in labs where the scientists are from all over the globe but one thing has remained constant, the research is run and funded by UK firms or the UK government. AstraZeneca is a British pharmaceutical company, one of the largest, and the main competitor to GlaxoSmithKline. It turns out that Pfizer, a US based company famous for bringing us Viagra, is launching an attempted takeover of AstraZeneca.

AstraZeneca Pfizer

Continue reading Pfizer meets stiff resistance to AstraZeneca takeover bid

Population Genetics: Methods and Findings (UCL Genetics Institute)

Yesterday I went to a talk at UCL. The evening was a “beer and pizza science evening” led by the UCL Genetics Institute in population genetics. Anyone with some sort of knowledge in this field would also realise that the beer and pizza would bring in a crowd despite the amount of not so popular statistics and modelling that can be involved. This was very true as the large gathering of people to the event somewhat dwindled after the half-time break. I however did stay until the end and was pleasantly surprised both at my ability to understand the talks and the actual content. Here I’ll summarise each one and give my own take on the topics.

Prof Mark Jobling was first and spoke about Y chromosome analysis. The Y chromosome is the smallest of the bunch and is somewhat neglected in sequencing projects and medical genetics. It is present in just males and in many instances it isn’t even included in higher organism genome releases purely because the subject chosen is female as this gives the added benefit of twice the amount of X chromosome for your money. However the potential in this little guy shouldn’t be underestimated.

The X chromosome next to the somewhat puny Y chromosome: small and mighty?
The X chromosome next to the somewhat puny Y chromosome: small and mighty?

The Y chromosome itself actually has very little sequence diversity and through custom sequencing of just this chromosome it is possible to map all the chunks of DNA across it and where they come from. The contents of these chunks and order of variation inside them can be called the haplotype. The novelty of comparing haplotypes across the Y chromosome with inherited surname shows that many men who think they are unrelated (despite actually having the same surname) are in fact descendants of common ancestors. In fact, a relatively rare version of the Y chromosome is common in almost all ‘Attenborough’ men that were sequenced! The idea behind all of this is that the Y chromosome appears to be under some strong purifying selection, although what that exactly is we can only guess (but most people believe it is some sexual/social advantage i.e. successful men have successful sons who have successful sons etc.). The personal gain from this talk was the confirmation that the methods behind this sequencing are very similar to mine and they are facing very similar problems to me. Woohoo, I am not alone!

Dr Simon Myers was the second speaker and he described his lab’s work on chromosome painting. When we inherit our chromosomes (one from mum, one from dad) they undergo recombination. That is bits from one chromosome in dad have crossed over and replaced the same bit from the paired chromosome in dad and therefore we get a mixture of both chromosomes from dad in just one chromosome. The same thing happens with the chromosome from mum and suddenly we realise that we have a mix of bits from all 4 grandparents in the 2 chromosomes. The image below goes might help explain that…

recombination

Now what his lab have done is trace these bits of chromosome back across many generations and painted all the differently inherited bits in different colours. Well they haven’t manually done this; they have a big fancy computer algorithm to do the maths. But from this information you can look at a modern day person and see how ‘African’ they are or how ‘East Asian’ they are based on their inherited chromosome segments. What’s then nice to do is show that these descriptions of modern populations follow patterns of ancient large-scale and more modern small scale human migration patterns. Plus there are lots of pretty colours to look at…

Dr Daniel Lawson was the first speaker after the beer and pizza break so had a smaller audience to contend with. The talk was a lot more maths/statistics/programming/algorithm stuff that often goes over my head but at least I understood the reasoning behind the concept. I often talk about sequencing and whole genomes but what can be difficult to comprehend is the enormity of this data. The total length of the human genome is over 3 billion base pairs, now multiply that by however many people you are sequencing and your computer can get really slow! Now the genome can supposedly be sequenced in its entirety for $1000 we are going to get a lot more data, but how do we handle this? The current algorithms and models can’t be scaled up easily as the estimates of important parameters actually get worse with more data! We have to look for analytics rather than models to generate our data. Now the rest of the talk was describing the specific algorithm Dr Lawson has been working on which seems to iteratively select a samples to estimate off of but I’d be lying if I said I understood any more. I have a lot of reading to go and do!

Prof Mark Thomas was the final speaker and he works on detecting signals of recent selection using ancient DNA data. Again, I’d like to brush over the statistics and modelling and talk more about the applications and ideas. There are a few aspects of modern humans that have so obviously been strongly selected for. A key one is lactase persistence – the ability to digest lactose from milk. It is a western thing really and you may even know many East Asian descendants who are lactose intolerant. Oddly enough there are many known (and unknown) mutations that lead to the persistence of the enzyme lactase into adulthood. This shows convergent evolution: different pathways have led to the same outcome. The benefit of being able to drink milk and eat dairy was, at some point in the past, so strong in Western Europe that people who couldn’t effectively died out! The map below shows lactase persistence (people who can digest lactose in adulthood) in red and lactose intolerance in blue.

fig1

It can be shown that this emergence of lactase persistence did not occur from natural genetic drift and was definitely the result of high selection pressure.The same effect can be seen in the blue eye pigmentation in Western Europe and the development of lighter skin. The question of ‘why?’ is one I don’t think we can ever answer for sure but a lot of people have their own theories. A strong case is put forward for the change from a fishing diet to an agricultural farming one where vitamin D and calcium deficiencies left people needing to be able to drink milk and use UVB rays from the sun to make a form of vitamin D in their skin. However this doesn’t explain the blue eyes part, at all. No one can. I’d speculate that the sudden emergence of a child with blue eyes would either be seen as an outsider or someone special so I wouldn’t be surprised if it just so happened that people with blue eyes simply looked hotter and preferentially reproduced with each other in some form of blue eyed revolution! But like I said, sexual/social selection can only be guessed, but it is fun to do so, I mean, look at this fitty:

Swarthy, blue-eyed caveman revealed using DNA from ancient tooth
Swarthy, blue-eyed caveman revealed using DNA from ancient tooth

Find the story in the guardian here.