Saturday, 19 January 2013

Max Perutz 2012 entry

Wow, I hadn't realised how long it's been since my last blog post - I blame the copious amount of food I ate over the holidays, and then the giant pile of work I've been doing since.

So, in order to keep the ball rolling, I thought I'd post a bit of science communication I wrote for my entry in last year's Max Perutz writing competition.

I was going to write an entry for the recent Euro-PMC competition, but I only got as far as deciding on the theme of the pun for my title (I was thinking something cheesy like 'Genius, or geneious?').

Anyway, here's the article as I wrote it last May (I didn't win).

Unravelling the secrets of our immune system

Sometimes we only realise how important something is when it goes wrong. In the case of adaptive immunity, things going wrong can be fatal.

Adaptive immunity is one of the systems we have evolved to keep infectious germs at bay. It is our intelligent protection system, a biological firewall, where white blood cells patrol our bodies, keeping us safe from disease. Not only does it stop intruders in their tracks, it remembers the threats it's seen before, so it can defend against them faster the next time they attack.

There are two medical conditions in humans that reveal to us how important it is to have a working adaptive immune system. The first occurs when some children are born without working copies of genes that encode important immune molecules. This means they don't make some of the proteins that are required for adaptive immunity to develop.

Alternatively, people can lose their resistance to microbes later in life. This can happen when untreated HIV positive individuals develop AIDS, or in transplant patients who have taken suppressive drugs to prevent organ rejection.

People without a functioning adaptive immune system are compromised, exposed. They are at risk from any stray infection, vulnerable to all manner of viruses, bacteria and fungi. A simple bug that might not even give you a temperature could spell death to them.

This makes it important for us to know how adaptive immunity works. This is what I do in my research; I look at a particular aspect of this system, to try and understand what a healthy adaptive immune system 'looks' like, and how it goes wrong in disease.

In order to explain my work, you have to know a little bit about how our bodies generate this powerful immunity.

Cells don't have eyes or ears, so they have to use receptor molecules on their surface to detect what's going on around them in their environment. These receptors are proteins, the blueprints for which are encoded in the genes in our DNA.

This means white blood cells could have a receptor that recognises a certain bit of a bacteria say, or the fragment of the outside of a virus. If the receptor finds and binds its target, then that cell can tell that the body is infected with a particular parasite.

The problem lies in that there are far more bugs and germs out there that could potentially infect us then there are genes in our genome. How can we have evolved ways to detect and protect against such a barrage of disease with so few genes?

Maturing adaptive immune cells overcome our finite genomes by shuffling pieces of it around, making unique receptor genes out of genetic building blocks that all our cells contain. These cells, called T cells and B cells, physically loop the DNA over itself, and then cut out the chunks in between.

This means different sections can be moved next to each other, recombining to create new genes. Incidentally, this extraordinary feature makes them some of the only cells in the body that don't share the same genome as all the other cells.

Each developing cell shuffles their DNA around independently, stitching different gene segments together in order to produce its own distinctive receptor. As there are many segments to choose from, the number of different combinations is huge.

Moreover, the DNA sequence at the join sites can be randomly altered, meaning the eventual number of possible different receptor genes is truly phenomenal. The fact that we have millions of white blood cells inside us, each bearing one of the trillions of different potential receptors, has historically kept researchers from measuring this diversity.

My project is to use DNA sequencing technology – developed during the Human Genome Project – to read as many of these uniquely generated adaptive immune genes as we can. By doing this we can characterise a person's immune repertoire, seeing how prepared their body is to fight off infection, and perhaps even see what they’ve been infected by in the past. 

The hope is that we can use this technology to understand what it is that makes a healthy human immune system. Once we know this, we can compare this to the compromised or failing immune systems that we see in infection, cancer and autoimmunity, and maybe get an insight into how to treat or avoid these conditions.

Science has brought a lot of relief to those suffering from disease, and has prevented many more from joining them. However, the challenges faced in curing our ills can only be surmounted by learning as much as possible about the way that our bodies work, as well as the diseases that threaten us. Unravelling the secrets of our immune systems is another step towards that goal.

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