Raising Money for Cystic Fibrosis

When CF was first described by Dorothy Anderson in 1938 life expectancy was an abysmal 4.  Now it is into the late 30s and due to the hard work of researchers and clinicians, should go considerably further as this figure is based on people who grew up long before today’s technologies.  Indeed the first time I met someone with CF was on a British Airways 747 when I was coming out to Vancouver for an interview for my current job.  I was reading my PhD thesis as my defence was the following week (tip to those doing PhDs, do not travel 8 time zones the week before a defence!!!).   He was in his 30s, seemed healthy and was working for a major international company.

In order to reach the goal of ‘cure found’ research in CF necessarily is done on a number of levels.  The cause of CF seems reasonably clear – a mutation in a gene called the cystic fibrosis transmembrane conductance regulator (easier to just know it as the CFTR) – so much work goes on into trying to find ways to fix that.  In theory it should be possible to fix that one gene by supplying cells with a copy of the gene that is normal and works properly.  Myself, I think that is probably the best hope for a cure because it would fix the underlying defect,  although I do not speak from a position of expertise on gene therapy.  Unfortunately there remain a lot of hurdles to get gene therapy working for CF, but work goes on.

In the history of CF nearly all the progress made has been made by research into understanding the consequences of CF.  CF was originally described as cystic fibrosis of the pancreas, a reflection of the problems people with CF have with digestion, this led to the development of drugs to aid digestion.  One of the big problems with CF is that the defective CFTR protein made by the CFTR gene is unable to perform its job of transporting chloride ions.  This might sound a bit obscure to non-scientists, but in essence what happens is that many of the lining of the bodies, such as in the pancreatic ducts – and critically for CF – in the lung, become coated in a thick sticky mucous.  In the pancreas and the digestive system this means that food can not be properly digested. 

In the lung this is a problem.  When you breathe in you breath all the air and its contents straight into your lungs.  Although you can’t see it, air can be full of all sorts of things from particulate matter to full living organisms in the form of microbes.  Normal healthy lungs have a mechanism to deal with this; they trap the organisms in the normal mucous lining the lungs and then these tiny hairs called cilia are used to push this mucous out of the lung and into the throat where it goes down into the stomach and stomach acid kills the microbes.

Pseudomonas aeruginosa the principal CF pathogen:

In CF it is thought the mucous that lines the lungs becomes thick and sticky as a result of the CFTR not working.  It becomes so thick and sticky that the cilia are unable to move it and it just stays there in the lung.  This presents a couple of significant problems for people with CF.  First this sticky mucous builds up in their lungs leading and must be removed by physiotherapy to stop it blocking breathing.  Secondly it becomes a breeding ground for some bacteria (and also some other microbes) that find it a nice little niche in which to live.  Some of these you may have heard of: Staphylococcus aureus is one, which is well known when it becomes very resistant to antibiotics (when it is known as MRSA).  However, the two biggest concerns are bacteria called Pseudomonas aeruginosa and another collection of bacteria known as the Burkholderia cepacia complex. 

This is where I come in, I have worked on both these bacteria.  I’m a microbiologist by training and have for a long time been interested in understanding how bacteria work and have always done this with half an eye on the significance of this in the context in CF.  I did my PhD on Pseudomonas aeruginosa and how that is able to make the notorious poison hydrogen cyanide.  Cyanide works by poisoning the mechanism most living cells use to make energy, however some bacteria have means of getting round this enabling them to resist much higher concentrations of cyanide so I was also interested in how Pseudomonas aeruginosa does this.

Right now I am working on the Burkholderia cepaciacomplex.   Whilst most people with CF will sooner or later become colonised with Pseudomonas, Burkholderia cepacia complex will infect only a minority.  However infection with these organisms is generally thought to be bad news because some of them can prove to be particularly problematic.

One of the problems with Burkholderia cepacia complex is that when someone gets infected with it the prognosis is not clear.  Sometimes people infected with it can become clear it, sometimes they can become chronically infected for a long time and sometimes they can decline very rapidly.  This is obviously a source of major concern to any one who has CF.  The reason I came to this lab was that it is almost unique in the world in allowing me to look samples of bacteria from the beginning to the very end of an infection.  This is what I’m now doing, to look at if there are ways we can determine ahead of time which Burkholderia cepacia complex infections are going to be worse than others.