Fixing the Leak

Fixing the Leak

So as I am spending the majority of my time writing my thesis right now (I know, it’s got to get done somehow) I thought I’d share with you a bit about what I’ve been researching.

WAIT! Before you decide this post is going to be too heavy and techy for you give me a moment to persuade you otherwise. So a few months ago I entered this PhD writing competition where the challenge was to basically explain your research to the average Joe ( yes I was thinking dodgeball then too) in 800 words. So I thought I’d have a crack at it. Turns out I haven’t been shortlisted but it’s their loss anyway (it’s not like I needed the prize money anyway.. ahem). Well, anyway here it is, let me know what you think…

Drip. Drip. Drip. You get up, walk into the kitchen – no, you didn’t leave the tap on again. Drip. Where is that coming from? Walking back into the living room you notice that there seems to have grown an unusual bulge on the ceiling coincidentally in the corner that is directly beneath the bathroom. And yes, the surrounding wallpaper is damp. I think it is time to call the plumber.

What if it wasn’t the pipes in your house that were leaking but your own biological plumbing, your blood vessels? Well, just like water pipes in your house distribute water, your blood vessels enable the distribution of blood throughout the body. In doing so they allow for the delivery of vital nutrients and oxygen as well as the collection and disposal of waste products such as carbon dioxide and urea; and in the same way that sometimes our household plumbing can stop working the way it is designed to and start leaking, so too can our blood vessels.

Interestingly, increased leakiness of blood vessels is a problem that is very rarely found on it’s own. It is more often associated with other illnesses including Age-related Macular Degeneration (AMD) which is the leading cause of vision loss in the UK, Cardiovascular disease – usually due to increased inflammation or an inadequate blood supply to the heart, lungs or brain (known as Ischemia) and some cancers, such as a type of brain tumour called Glioblastoma. In all three cases the increase in leaky vessels is associated with the growth of new vessels in the diseased area that have not received the correct signals. This leads to a new network of blood vessels that is in utter chaos – think traffic lights are broken at a major junction during rush hour kind of chaos. You can end up with the oxygen rich blood mixing with the blood containing the waste products, blood trying to flow the wrong way and even an area of the surrounding tissue bathed in fluid that has wrongly been allowed to leak out.

Like any other organ in your body, blood vessels are made up of several different types of cells that usually all work together. At their most basic level blood vessels are tubes formed by endothelial cells. Other types of cells, which help define whether it will become an artery, vein or capillary, then surround the endothelial cells. In order to grow new vessels in a process known as angiogenesis the endothelial cells that form the tight-knit vascular tube must loosen their grip on adjacent cells, this enables the cells to divide or migrate constructing a new tube that sprouts from the original one. So there must be some kind of mechanism that either prevents the endothelial cells from loosing contact with each other completely or blocks the blood and it’s components from leaking out.

This is where my work comes in. I am delving into the inner workings of blood vessels and trying to understand why when vessels grow in normal circumstances, for instance due to increased exercise or during the menstruation cycle, they do not leak whereas as in some disease situations they do.

I have found that two particular proteins, named Delta-like Ligand 4 (Dll4) and Notch, found on the surface of adjacent endothelial cells are key in controlling the leakiness of normal vessels. These two proteins were already known to be involved in regulating angiogenesis and with the discovery that they are also involved in controlling vessel leakiness the pieces of the jigsaw begin fitting together nicely. Additionally, abnormal levels of the Dll4 protein have been seen in diseases where increased vessel leakiness is a known issue making my theory that the Dll4 – NOTCH proteins control the leakiness of a vessel start to look watertight.

My research may just be one, small piece of the huge, as yet unfinished, vascular jigsaw but by fitting one piece together with another and then another and so on you eventually discover the big picture. By connecting each piece together we may be able to fix the broken traffic lights at that major junction, or in the case of cancer, allow the chemotherapy drugs to be able to target the tumour more directly. This could mean less drugs would be needed to get the same result and therefore fewer side effects for the patient and less expense for the NHS.

Although there is still a lot of work to get to this point, without my piece of the jigsaw you may still be able to see the overall picture, however, it is only when you incorporate my piece that we will really understand our vessels and be able to affect patients’ lives for the better.

 

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